SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

[email protected]

SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

[email protected]

SNOWMASS, COLO. – By far the most-important contributor to improved outcomes following out-of-hospital cardiac arrest during the past decade has been therapeutic hypothermia, Dr. N.A. Mark Estes III said at the Annual Cardiovascular Conference at Snowmass.

The No. 1 cause of in-hospital death in patients who arrive at the hospital with a perfusable rhythm following resuscitation from out-of-hospital cardiac arrest isn’t sepsis, hepatic or renal failure, or cardiogenic shock. It’s neurologic death caused by anoxic brain injury, which begins several hours after cardiac arrest and continues for about 48 hours. This is where therapeutic hypothermia has made a huge difference, said Dr. Estes, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

“One-half of out-of-hospital cardiac arrest survivors experience secondary anoxic brain damage of varying degrees. Until recently, there was no treatment with documented efficacy in preventing this damage. Despite multiple agents being looked at for neuroprevention, none really has worked. But therapeutic hypothermia has drastically improved outcomes. More than half of patients who arrive at the hospital with a perfusable rhythm and receive therapeutic hypothermia are discharged relatively neurologically intact. That’s a huge difference from what we used to see,” the electrophysiologist observed.

Indeed, the proportion of U.S. patients who experience out-of-hospital cardiac arrest and survive to hospital discharge neurologically intact is “dismal” at about 10%, he noted.

Virtually all specialized cardiac arrest centers now provide therapeutic hypothermia using various protocols. The demonstrated effectiveness of this postresuscitation therapy was an impetus for the American Heart Association policy statement calling for creation of regional cardiac resuscitation systems of care (Circulation. 2010 Feb 9;121[5]:709-29). To date, however, such organized systems exist in only a handful of states or portions of states.

Nonetheless, when an out-of-hospital cardiac arrest patient arrives at a community hospital that can’t provide emergency coronary angiography and therapeutic hypothermia, it’s appropriate to stabilize that patient in the emergency department and then transfer to a hospital that can, according to Dr. Estes.

The mechanism by which therapeutic hypothermia works has been well elucidated. The treatment curbs the process by which ischemia as a second blow triggers formation of oxygen free radicals, glutamate release, calcium shifts, and mitochondrial dysfunction, with resultant destruction of brain tissue.

Roughly 250,000 sudden cardiac deaths (SCDs) occur annually in this country. In addition to more widespread availability of therapeutic hypothermia and other forms of specialized postresuscitation care through creation of regional systems of care for out-of-hospital cardiac arrest, there are other opportunities for improving outcomes. These include earlier activation of the chain of survival that begins with a bystander dialing 911 as well as greater availability of public access defibrillation.

Dr. Estes emphasized that while these measures will further improve outcomes of cardiac arrest, they won’t actually reduce its frequency. By far the greatest opportunity in that realm lies in primordial prevention of coronary artery disease; that is, prevention of the risk factors for CAD. After all, he noted, 80% of all SCDs are associated with underlying ischemic heart disease. In 30% of SCDs, the fatal event is the first manifestation of previously unrecognized CAD. Another one-third of SCDs occur in patients with known CAD, but who weren’t considered at high risk for SCD because of their preserved left ventricular ejection fraction.

“There are a number of luminaries in the field who feel that if we’re really going to make an impact on sudden cardiac death, it’s going to be through primordial prevention of CAD,” the cardiologist said.

For this reason, he was thrilled to hear Dr. Robert A. Vogel elsewhere at the conference describe research by investigators at Affiris AG in Vienna who’ve created a peptide-based vaccine that inhibits PCSK9. Moreover, they showed it to be effective in sharply lowering LDL in mice (PLoS One. 2014 Dec 4;9[12]:e114469).

“I believe that in my lifetime, we will have an antiatherosclerotic vaccine that will lower LDL to an extent where this disease will not disappear but may get to a manageable extent, perhaps a 10% lifetime risk instead of the 55% lifetime risk of MI or stroke that we as Americans currently have,” predicted Dr. Vogel of the University of Colorado, Denver.

Dr. Vogel reported serving as a consultant to the National Football League and the Pritikin Longevity Center as well as acting as the national coordinator for the Sanofi-sponsored ODYSSEY Outcomes trial studying the PCSK9 inhibitor alirocumab (Praluent).

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

[email protected]

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.

A European expert group has proposed several revisions to the 2010 McDonald criteria for the use of MRI in diagnosing multiple sclerosis.

The MAGNIMS collaborative research network argued that new data on the application of MRI, as well as improvements in MRI technology, demanded changes to the multiple sclerosis (MS) diagnostic criteria.

The first proposed recommendation is that three or more focal lesions, rather than a single lesion, should be present to diagnose the involvement of the periventricular region and to show disease dissemination in space (Lancet Neurol. 2016 Jan 25. doi: 10.1016/S1474-4422[15]00393-2).

HUNG KUO CHUN/Thinkstock

“A single lesion was deemed not sufficiently specific to determine whether involvement of the periventricular region is due to a demyelinating inflammatory event, and the use of one periventricular lesion for assessing dissemination in space has never been formally validated,” wrote Dr. Massimo Filippi of Vita-Salute San Raffaele University, Milan, and his coauthors.

They also pointed out that incidental periventricular lesions can be found in up to 30% of patients with migraine, and in individuals with other neurologic disorders.

In addition, the group recommended that optic nerve lesions be added to the criteria for dissemination in space.

“Clinical documentation of optic nerve atrophy or pallor, neurophysiological confirmation of optic nerve dysfunction (slowed conduction), or imaging features of clinically silent optic nerve inflammation (MRI lesions or retinal nerve fiber layer thinning) support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time.”

According to the new recommendations, disease dissemination in space can be shown by the involvement of at least two areas from a list of five possibilities: three or more periventricular lesions, one or more infratentorial lesions, one or more spinal cord lesions, one or more optic nerve lesions, or one or more cortical or juxtacortical lesions.

However, the group did not propose any significant changes to the criteria for dissemination in time, other than saying that the presence of nonenhancing black holes should not be considered as a potential alternative criterion to show dissemination in time in adult patients.

The committee also backed the existing recommendations that children aged 11 years or older with nonacute disseminated encephalomyelitis–like presentation should be diagnosed with the same criteria as adults, for dissemination in time and space.

“Several studies have confirmed that the 2010 McDonald criteria perform better than or similar to previously proposed pediatric MS criteria for diagnosis of children with nonacute disseminated encephalomyelitis presentations and pediatric patients older than 11 years, and the consensus group therefore recommend caution when using these criteria in children younger than 11 years,” they wrote.

Other recommendations include that there be no distinction required between symptomatic and asymptomatic MRI lesions for diagnosing dissemination in time or space; that the whole spinal cord be imaged to define dissemination in space, particularly in patients who do not fulfill the brain MRI criteria; and that the same criteria for dissemination in space be used for both primary progressive MS and relapse-onset MS, with cerebrospinal fluid results considered for clinically uncertain cases of primary progressive MS.

The expenses of the workshop where the recommendations were formulated were supported by an unrestricted educational grant from Novartis. The authors of the paper declared grants, consultancies, speaking fees, travel support, and honoraria from numerous pharmaceutical companies, including Novartis.

A European expert group has proposed several revisions to the 2010 McDonald criteria for the use of MRI in diagnosing multiple sclerosis.

The MAGNIMS collaborative research network argued that new data on the application of MRI, as well as improvements in MRI technology, demanded changes to the multiple sclerosis (MS) diagnostic criteria.

The first proposed recommendation is that three or more focal lesions, rather than a single lesion, should be present to diagnose the involvement of the periventricular region and to show disease dissemination in space (Lancet Neurol. 2016 Jan 25. doi: 10.1016/S1474-4422[15]00393-2).

HUNG KUO CHUN/Thinkstock

“A single lesion was deemed not sufficiently specific to determine whether involvement of the periventricular region is due to a demyelinating inflammatory event, and the use of one periventricular lesion for assessing dissemination in space has never been formally validated,” wrote Dr. Massimo Filippi of Vita-Salute San Raffaele University, Milan, and his coauthors.

They also pointed out that incidental periventricular lesions can be found in up to 30% of patients with migraine, and in individuals with other neurologic disorders.

In addition, the group recommended that optic nerve lesions be added to the criteria for dissemination in space.

“Clinical documentation of optic nerve atrophy or pallor, neurophysiological confirmation of optic nerve dysfunction (slowed conduction), or imaging features of clinically silent optic nerve inflammation (MRI lesions or retinal nerve fiber layer thinning) support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time.”

According to the new recommendations, disease dissemination in space can be shown by the involvement of at least two areas from a list of five possibilities: three or more periventricular lesions, one or more infratentorial lesions, one or more spinal cord lesions, one or more optic nerve lesions, or one or more cortical or juxtacortical lesions.

However, the group did not propose any significant changes to the criteria for dissemination in time, other than saying that the presence of nonenhancing black holes should not be considered as a potential alternative criterion to show dissemination in time in adult patients.

The committee also backed the existing recommendations that children aged 11 years or older with nonacute disseminated encephalomyelitis–like presentation should be diagnosed with the same criteria as adults, for dissemination in time and space.

“Several studies have confirmed that the 2010 McDonald criteria perform better than or similar to previously proposed pediatric MS criteria for diagnosis of children with nonacute disseminated encephalomyelitis presentations and pediatric patients older than 11 years, and the consensus group therefore recommend caution when using these criteria in children younger than 11 years,” they wrote.

Other recommendations include that there be no distinction required between symptomatic and asymptomatic MRI lesions for diagnosing dissemination in time or space; that the whole spinal cord be imaged to define dissemination in space, particularly in patients who do not fulfill the brain MRI criteria; and that the same criteria for dissemination in space be used for both primary progressive MS and relapse-onset MS, with cerebrospinal fluid results considered for clinically uncertain cases of primary progressive MS.

The expenses of the workshop where the recommendations were formulated were supported by an unrestricted educational grant from Novartis. The authors of the paper declared grants, consultancies, speaking fees, travel support, and honoraria from numerous pharmaceutical companies, including Novartis.

A European expert group has proposed several revisions to the 2010 McDonald criteria for the use of MRI in diagnosing multiple sclerosis.

The MAGNIMS collaborative research network argued that new data on the application of MRI, as well as improvements in MRI technology, demanded changes to the multiple sclerosis (MS) diagnostic criteria.

The first proposed recommendation is that three or more focal lesions, rather than a single lesion, should be present to diagnose the involvement of the periventricular region and to show disease dissemination in space (Lancet Neurol. 2016 Jan 25. doi: 10.1016/S1474-4422[15]00393-2).

HUNG KUO CHUN/Thinkstock

“A single lesion was deemed not sufficiently specific to determine whether involvement of the periventricular region is due to a demyelinating inflammatory event, and the use of one periventricular lesion for assessing dissemination in space has never been formally validated,” wrote Dr. Massimo Filippi of Vita-Salute San Raffaele University, Milan, and his coauthors.

They also pointed out that incidental periventricular lesions can be found in up to 30% of patients with migraine, and in individuals with other neurologic disorders.

In addition, the group recommended that optic nerve lesions be added to the criteria for dissemination in space.

“Clinical documentation of optic nerve atrophy or pallor, neurophysiological confirmation of optic nerve dysfunction (slowed conduction), or imaging features of clinically silent optic nerve inflammation (MRI lesions or retinal nerve fiber layer thinning) support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time.”

According to the new recommendations, disease dissemination in space can be shown by the involvement of at least two areas from a list of five possibilities: three or more periventricular lesions, one or more infratentorial lesions, one or more spinal cord lesions, one or more optic nerve lesions, or one or more cortical or juxtacortical lesions.

However, the group did not propose any significant changes to the criteria for dissemination in time, other than saying that the presence of nonenhancing black holes should not be considered as a potential alternative criterion to show dissemination in time in adult patients.

The committee also backed the existing recommendations that children aged 11 years or older with nonacute disseminated encephalomyelitis–like presentation should be diagnosed with the same criteria as adults, for dissemination in time and space.

“Several studies have confirmed that the 2010 McDonald criteria perform better than or similar to previously proposed pediatric MS criteria for diagnosis of children with nonacute disseminated encephalomyelitis presentations and pediatric patients older than 11 years, and the consensus group therefore recommend caution when using these criteria in children younger than 11 years,” they wrote.

Other recommendations include that there be no distinction required between symptomatic and asymptomatic MRI lesions for diagnosing dissemination in time or space; that the whole spinal cord be imaged to define dissemination in space, particularly in patients who do not fulfill the brain MRI criteria; and that the same criteria for dissemination in space be used for both primary progressive MS and relapse-onset MS, with cerebrospinal fluid results considered for clinically uncertain cases of primary progressive MS.

The expenses of the workshop where the recommendations were formulated were supported by an unrestricted educational grant from Novartis. The authors of the paper declared grants, consultancies, speaking fees, travel support, and honoraria from numerous pharmaceutical companies, including Novartis.

ORLANDO – When treating rosacea, consider adding cosmeceuticals to more conventional prescriptions and over-the-counter treatments to improve the management of symptoms and patient satisfaction.

The recommendation comes from Dr. Julie Harper, a dermatologist at the University of Alabama-Birmingham, who spoke about the benefits of cosmeceuticals for rosacea at the Orlando Dermatology Aesthetic and Clinical Conference.

“I see about 40 people a day on my regular dermatology days [and] it’s easy to just write a prescription and hand it to that rosacea patient, but you do them a big disservice when you do that,” explained Dr. Harper. “We’ve got to talk about triggers, about skin care, about sun protection, [and] start that discussion from there.”

The most-important point for patients to understand is the main triggers of their rosacea, which can include ultraviolet light, spices, stress, exercise, heat, barrier disruption, and Demodex. Since sunlight is the No. 1 trigger for rosacea, treatment strategies often need to start there and revolve around how to avoid or manage the condition based on sun exposure.

As for cosmeceuticals, Dr. Harper focused on three types that have been shown to be effective against rosacea: niacinamide, licorice, and green tea.

The available data on niacinamide for rosacea are primarily from the 2006 Nicomide Improvement in Clinical Outcomes Study (NICOS), an open-label, multicenter, prospective cohort study that recruited people with acne vulgaris and acne rosacea from 100 centers and administered 750 mg of niacinamide with zinc and copper, while some got niacinamide plus oral antibiotics. The 49 people with rosacea who were enrolled received baseline assessments in the clinic, but 4-week and 8-week follow-ups were done via self-reported surveys (Cutis. 2006 Jan;77[1 Suppl]:17-28).

At 8 weeks, “75% of the rosacea group reported that appearance of their rosacea was moderately or much better [and] that there was also significant reduction in inflammatory lesions,” Dr. Harper said. “There was not a big difference in the group that had an oral antibiotic and niacinamide, versus niacinamide without the oral antibiotic,” although the design of the study leaves the findings somewhat questionable, she noted.

Topical niacinamide also has the potential to benefit certain rosacea patients, she said, referring to a 2005 study examining the effects of a niacinamide-containing moisturizer on the face and one forearm of 50 patients over 4 weeks. The primary outcome of the trial was barrier function, as measured by a dimethyl sulfoxide (DMSO) chemical probe (Cutis. 2005 Aug;76[2]:135-41).

While the results of this trial are “difficult” to interpret – due largely to the lack of any real measurement of facial improvement in barrier function and the confusion over whether any improvement on the forearm can be attributed to the niacinamide specifically or to the moisturizer itself – “long story short, niacinamide did seem to help the barrier function in this particular study,” Dr. Harper said. The takeaway, therefore, is that topical niacinamide treatments may offer some value to certain patients.

Moving on to licorice, Dr. Harper discussed an open label study recently published online in the Journal of the European Academy of Dermatology and Venereology, in which subjects were given a complete skin care system – which contained a cleanser, a day cream, a night cream, and a concealer product containing licochalcone A (licorice extract). They were evaluated over a period of 8 weeks for improvement in erythema, burning, stinging, tingling, and tightness, all of which were measured at baseline (J Eur Acad Dermatol Venereol. 2016 Feb;30 Suppl 1:21-7).

Results showed “improvement of statistical significance,” Dr. Harper said. “All groups had improvement over time, and did better at 8 weeks than at 4 weeks [although] the rosacea group did not reach statistical significance until week 8.”

Finally, with green tea, Dr. Harper pointed to a 2010 randomized double-blind split-face study of just four healthy individuals with erythema and telangiectasia of the face, treated for 6 weeks with a cream containing epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, on one side of their face; a vehicle cream was applied to the other side and punch biopsies were performed to determine improvements (Int J Clin Exp Pathol. 2010;3[7]:705-9). EGCG cream was used because of its “antioxidant, immunomodulatory, photoprotective, antiangiogenic – that’s the standout here, that’s what we really need – and anti-inflammatory properties,” Dr. Harper said.

While biopsies did not reveal any changes to facial vasculature, there “was a significant reduction in hypoxia-inducible factor-1 and VEGF [vascular endothelial growth factor],” which are both markers of angiogenesis – indicating some degree of usefulness against rosacea, Dr. Harper said. However, a longer, more definitive study would be needed to substantiate these findings, she added.

Dr. Harper did not report any relevant financial disclosures.

[email protected]

ORLANDO – When treating rosacea, consider adding cosmeceuticals to more conventional prescriptions and over-the-counter treatments to improve the management of symptoms and patient satisfaction.

The recommendation comes from Dr. Julie Harper, a dermatologist at the University of Alabama-Birmingham, who spoke about the benefits of cosmeceuticals for rosacea at the Orlando Dermatology Aesthetic and Clinical Conference.

“I see about 40 people a day on my regular dermatology days [and] it’s easy to just write a prescription and hand it to that rosacea patient, but you do them a big disservice when you do that,” explained Dr. Harper. “We’ve got to talk about triggers, about skin care, about sun protection, [and] start that discussion from there.”

The most-important point for patients to understand is the main triggers of their rosacea, which can include ultraviolet light, spices, stress, exercise, heat, barrier disruption, and Demodex. Since sunlight is the No. 1 trigger for rosacea, treatment strategies often need to start there and revolve around how to avoid or manage the condition based on sun exposure.

As for cosmeceuticals, Dr. Harper focused on three types that have been shown to be effective against rosacea: niacinamide, licorice, and green tea.

The available data on niacinamide for rosacea are primarily from the 2006 Nicomide Improvement in Clinical Outcomes Study (NICOS), an open-label, multicenter, prospective cohort study that recruited people with acne vulgaris and acne rosacea from 100 centers and administered 750 mg of niacinamide with zinc and copper, while some got niacinamide plus oral antibiotics. The 49 people with rosacea who were enrolled received baseline assessments in the clinic, but 4-week and 8-week follow-ups were done via self-reported surveys (Cutis. 2006 Jan;77[1 Suppl]:17-28).

At 8 weeks, “75% of the rosacea group reported that appearance of their rosacea was moderately or much better [and] that there was also significant reduction in inflammatory lesions,” Dr. Harper said. “There was not a big difference in the group that had an oral antibiotic and niacinamide, versus niacinamide without the oral antibiotic,” although the design of the study leaves the findings somewhat questionable, she noted.

Topical niacinamide also has the potential to benefit certain rosacea patients, she said, referring to a 2005 study examining the effects of a niacinamide-containing moisturizer on the face and one forearm of 50 patients over 4 weeks. The primary outcome of the trial was barrier function, as measured by a dimethyl sulfoxide (DMSO) chemical probe (Cutis. 2005 Aug;76[2]:135-41).

While the results of this trial are “difficult” to interpret – due largely to the lack of any real measurement of facial improvement in barrier function and the confusion over whether any improvement on the forearm can be attributed to the niacinamide specifically or to the moisturizer itself – “long story short, niacinamide did seem to help the barrier function in this particular study,” Dr. Harper said. The takeaway, therefore, is that topical niacinamide treatments may offer some value to certain patients.

Moving on to licorice, Dr. Harper discussed an open label study recently published online in the Journal of the European Academy of Dermatology and Venereology, in which subjects were given a complete skin care system – which contained a cleanser, a day cream, a night cream, and a concealer product containing licochalcone A (licorice extract). They were evaluated over a period of 8 weeks for improvement in erythema, burning, stinging, tingling, and tightness, all of which were measured at baseline (J Eur Acad Dermatol Venereol. 2016 Feb;30 Suppl 1:21-7).

Results showed “improvement of statistical significance,” Dr. Harper said. “All groups had improvement over time, and did better at 8 weeks than at 4 weeks [although] the rosacea group did not reach statistical significance until week 8.”

Finally, with green tea, Dr. Harper pointed to a 2010 randomized double-blind split-face study of just four healthy individuals with erythema and telangiectasia of the face, treated for 6 weeks with a cream containing epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, on one side of their face; a vehicle cream was applied to the other side and punch biopsies were performed to determine improvements (Int J Clin Exp Pathol. 2010;3[7]:705-9). EGCG cream was used because of its “antioxidant, immunomodulatory, photoprotective, antiangiogenic – that’s the standout here, that’s what we really need – and anti-inflammatory properties,” Dr. Harper said.

While biopsies did not reveal any changes to facial vasculature, there “was a significant reduction in hypoxia-inducible factor-1 and VEGF [vascular endothelial growth factor],” which are both markers of angiogenesis – indicating some degree of usefulness against rosacea, Dr. Harper said. However, a longer, more definitive study would be needed to substantiate these findings, she added.

Dr. Harper did not report any relevant financial disclosures.

[email protected]

ORLANDO – When treating rosacea, consider adding cosmeceuticals to more conventional prescriptions and over-the-counter treatments to improve the management of symptoms and patient satisfaction.

The recommendation comes from Dr. Julie Harper, a dermatologist at the University of Alabama-Birmingham, who spoke about the benefits of cosmeceuticals for rosacea at the Orlando Dermatology Aesthetic and Clinical Conference.

“I see about 40 people a day on my regular dermatology days [and] it’s easy to just write a prescription and hand it to that rosacea patient, but you do them a big disservice when you do that,” explained Dr. Harper. “We’ve got to talk about triggers, about skin care, about sun protection, [and] start that discussion from there.”

The most-important point for patients to understand is the main triggers of their rosacea, which can include ultraviolet light, spices, stress, exercise, heat, barrier disruption, and Demodex. Since sunlight is the No. 1 trigger for rosacea, treatment strategies often need to start there and revolve around how to avoid or manage the condition based on sun exposure.

As for cosmeceuticals, Dr. Harper focused on three types that have been shown to be effective against rosacea: niacinamide, licorice, and green tea.

The available data on niacinamide for rosacea are primarily from the 2006 Nicomide Improvement in Clinical Outcomes Study (NICOS), an open-label, multicenter, prospective cohort study that recruited people with acne vulgaris and acne rosacea from 100 centers and administered 750 mg of niacinamide with zinc and copper, while some got niacinamide plus oral antibiotics. The 49 people with rosacea who were enrolled received baseline assessments in the clinic, but 4-week and 8-week follow-ups were done via self-reported surveys (Cutis. 2006 Jan;77[1 Suppl]:17-28).

At 8 weeks, “75% of the rosacea group reported that appearance of their rosacea was moderately or much better [and] that there was also significant reduction in inflammatory lesions,” Dr. Harper said. “There was not a big difference in the group that had an oral antibiotic and niacinamide, versus niacinamide without the oral antibiotic,” although the design of the study leaves the findings somewhat questionable, she noted.

Topical niacinamide also has the potential to benefit certain rosacea patients, she said, referring to a 2005 study examining the effects of a niacinamide-containing moisturizer on the face and one forearm of 50 patients over 4 weeks. The primary outcome of the trial was barrier function, as measured by a dimethyl sulfoxide (DMSO) chemical probe (Cutis. 2005 Aug;76[2]:135-41).

While the results of this trial are “difficult” to interpret – due largely to the lack of any real measurement of facial improvement in barrier function and the confusion over whether any improvement on the forearm can be attributed to the niacinamide specifically or to the moisturizer itself – “long story short, niacinamide did seem to help the barrier function in this particular study,” Dr. Harper said. The takeaway, therefore, is that topical niacinamide treatments may offer some value to certain patients.

Moving on to licorice, Dr. Harper discussed an open label study recently published online in the Journal of the European Academy of Dermatology and Venereology, in which subjects were given a complete skin care system – which contained a cleanser, a day cream, a night cream, and a concealer product containing licochalcone A (licorice extract). They were evaluated over a period of 8 weeks for improvement in erythema, burning, stinging, tingling, and tightness, all of which were measured at baseline (J Eur Acad Dermatol Venereol. 2016 Feb;30 Suppl 1:21-7).

Results showed “improvement of statistical significance,” Dr. Harper said. “All groups had improvement over time, and did better at 8 weeks than at 4 weeks [although] the rosacea group did not reach statistical significance until week 8.”

Finally, with green tea, Dr. Harper pointed to a 2010 randomized double-blind split-face study of just four healthy individuals with erythema and telangiectasia of the face, treated for 6 weeks with a cream containing epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, on one side of their face; a vehicle cream was applied to the other side and punch biopsies were performed to determine improvements (Int J Clin Exp Pathol. 2010;3[7]:705-9). EGCG cream was used because of its “antioxidant, immunomodulatory, photoprotective, antiangiogenic – that’s the standout here, that’s what we really need – and anti-inflammatory properties,” Dr. Harper said.

While biopsies did not reveal any changes to facial vasculature, there “was a significant reduction in hypoxia-inducible factor-1 and VEGF [vascular endothelial growth factor],” which are both markers of angiogenesis – indicating some degree of usefulness against rosacea, Dr. Harper said. However, a longer, more definitive study would be needed to substantiate these findings, she added.

Dr. Harper did not report any relevant financial disclosures.

[email protected]

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Terminalia chebula, a member of the Combretaceae family, is an evergreen plant found abundantly in India, Pakistan, China, Thailand, Sri Lanka, and Malaysia.^1,2 It has long been used in traditional medicine, particularly Ayurveda, as well as in Thai traditional medicine.³ It also has also been used for many years in the traditional medicine of the Samahni valley of Pakistan to treat chronic ulcers as well as dental caries and heart ailments.⁴ Other traditional indications include asthma and urinary disorders.⁵ In Thailand, it has been used to treat skin diseases and to promote wound healing and rejuvenation.¹ It is particularly known for its potent antioxidant and antimicrobial properties.⁶ The wide array of health benefits associated with T. chebula is attributed to its high content of phenolic compounds, flavonol glycosides, and other phytonutrients.⁷

Antioxidant, anti-aging, and depigmenting effects

In 2004, Na et al. observed that T. chebula fruit extract exerted an inhibitory effect on the age-dependent shortening of telomeres and UVB-induced oxidative damage in vitro.⁸

Kim et al. screened 50 Korean plants to identify natural sources of elastase and hyaluronidase inhibitors in 2010. The strong efficacy of T. chebula led the investigators to choose it for additional study in which the fruits of the methanol crude extract at 1 mg/mL demonstrated 80% elastase and 87% hyaluronidase inhibitory activities. In addition, the investigators isolated 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), which also exhibited significant inhibition of elastase and hyaluronidase and induction of type II collagen expression. The authors concluded that PGG has the potential as a cutaneous anti-aging agent posing no cytotoxicity concerns and warrants further in vivo study.⁹

A 2010 in vitro study of the anti-aging properties of the extracts of 15 plant species, including T. chebula galls, outgrowths that result from insect bites, was conducted by Manosroi et al. The cold aqueous extract of T. chebula manifested the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and highest stimulation index for proliferation of normal human skin fibroblasts. T. chebula, which also inhibited matrix metalloproteinase (MMP)-2 activity, was compared against compounds such as ascorbic acid, alpha-tocopherol, and butylated hydroxytoluene. The investigators concluded that their findings supported the traditional uses of T. chebula gall in Thai medicine and suggest that T. chebula would be beneficial for inclusion in new anti-aging formulations.³

Later that year, Manosroi et al. characterized the biological activities of the phenolic compounds isolated from T. chebula galls, finding that these compounds (gallic acid, punicalagin, isoterchebulin, 1,3,6-tri-O-galloyl-beta-D-glucopyranose, chebulagic acid, and chebulinic acid) exhibited greater radical-scavenging and melanin-inhibitory activity than the reference compounds ascorbic acid, butylated hydroxytoluene, alpha-tocopherol, arbutin, and kojic acid. Although the T. chebula constituents were less effective than the reference compounds in mushroom tyrosinase inhibition and human tumor cytotoxicity assays, the investigators concluded that the antioxidant and depigmenting activity of the constituents of T. chebula accounted for the beneficial profile of the plant that has emerged over time.¹⁰

The next year, Manosroi et al. assessed the cutaneous anti-aging effects of a gel containing niosomes incorporating a semi-purified fraction including gallic acid derived from T. chebula galls or outgrowths. Human volunteers were enlisted to test skin elasticity and roughness and rabbit skin was used to evaluate skin irritation. The gel containing the semi-purified fractions loaded in niosomes was compared with an unloaded fraction, revealing that the loaded niosomes yielded greater gallic acid chemical stability as well as in vivo anti-aging effects.¹¹ Earlier that year, the team had shown the viability of niosomes, particularly elastic ones, to promote chemical stability for the transdermal absorption of gallic acid in semipurified T. chebula gall fractions in rats. Their findings, they concluded, point to the potential for achieving topical anti-aging benefits from such formulations.¹²

yogesh_more/ Thinkstock.com

In 2012, Akhtar et al. developed a water-in-oil T. chebula formulation and assessed its effects on various parameters. The investigators prepared a base with no active ingredients and a 5% T. chebula formulation, which remained stable at various storage conditions. For 8 weeks, they applied the base as well as the formulation to the cheeks of human volunteers, with weekly evaluations indicating that the formulation as opposed to the base yielded significant improvement, irrespective of time elapsed, in skin moisture content and erythema. The authors concluded that their T. chebula topical cream was effective in rejuvenating human skin.¹³

Wound healing

In 2002, Suguna et al. investigated in vivo the effects of a topically administered alcohol extract of the leaves of T. chebula on the healing of rat dermal wounds. The researchers found that treatment with T. chebula accelerated wound healing, with improved contraction rates and shorter epithelialization periods. T. chebula treatment yielded a 40% increase in the tensile strength of tissues from treated wounds. The authors concluded that T. chebula is beneficial in speeding the wound healing process.²

Immature T. chebula fruit extracts high in tannins are thought to be effective in enhancing the wound healing process, according to Li et al., who found in 2011 that the extracts promoted wound healing in rats, likely due to the antibacterial and angiogenic potency of its tannins.¹

In a 2014 study on wound healing, Singh et al. observed in vitro that T. chebula extracts effectively scavenged free radicals in a DPPH assay and enhanced proliferation of keratinocytes and fibroblasts. They concluded that T. chebula can be considered for use as a bioactive approach to wound healing for its effects in promoting cellular proliferation and inhibiting production of free radicals.⁷

Other biologic activities

A 1995 study by Kurokawa et al. showed that T. chebula was one of four herbal extracts among 10 tested to exhibit a discrete anti–herpes simplex virus type 1 (HSV-1) activity in vitro when combined with acyclovir. Oral administration of the herbs with acyclovir in mice in doses corresponding to human use significantly limited skin lesion development and/or extended mean survival time of infected mice in comparison to any of the herbs or acyclovir used alone.¹⁴

Nam et al. used a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic symptoms in 2011 and found that a T. chebula seed extract attenuated atopic dermatitis symptoms, resulting in a 52% decrease in the immune response and lower eosinophil levels in nearby skin tissue.⁶

In 2013, Manosroi et al. found that various tannins and one oleanane-type triterpene acid isolated from T. chebula galls displayed strong inhibitory capacity against melanogenesis in mice, with one of the tannins (isoterchebulin) shown to decrease protein levels of tyrosinase, microphthalmia-associated transcription factor, and tyrosine-related protein 1 in mainly a concentration-dependent fashion. Another tannin and several triterpenoids were noted for suppressing 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammation. In addition, constituent phenols manifested strong radical-scavenging activity. In a two-stage carcinogenesis mouse model, the investigators observed that the triterpene acid arjungenin hindered skin tumor promotion after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion by TPA. Their findings indicate a wide range of biologic activity and potential health benefits associated with T. chebula.¹⁵

In a mouse study in 2014, Singh et al. determined that a new antifungal agent, an apigenin ointment containing extract of T. chebula stem, was effective in significantly reducing the fungal burden from the experimentally-induced dermatophyte Trichopython mentagrophytes. They suggested that this agent warrants consideration in clinically treating dermatophytosis in humans.¹⁶

Triphala, a traditional combination formulation

Long used in Ayurveda, triphala (the word is derived from the Sanskrit tri, three, and phala, fruits) is an antioxidant-rich herbal formulation that combines the dried fruits of T. chebula, Terminalia bellirica, and Emblica officinalis. Naik et al. observed, in a 2005 in vitro study of the aqueous extract of the fruits of T. chebula, T. bellirica, and E. officinalis, as well as their equiproportional mixture triphala, that T. chebula was the most effective at scavenging free radicals. They noted that triphala appears to synergistically combine the strengths of each of its primary components.¹⁷ Subsequent studies have demonstrated that triphala is a strong source of natural antioxidants and exhibits a wide range of beneficial activities, including free radical scavenging, antioxidant, anti-inflammatory, analgesic, antibacterial, antimutagenic, wound healing, antistress, adaptogenic, hypoglycemic, anticancer, chemoprotective, radioprotective, chemopreventive, and wound healing.^5,18-21

Extracts of T. chebula also have been combined with those of E. officinalis, T. bellirica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum in a polyherbal formulation (Aller-7/NR-A2) that has been found safe for the treatment of allergic rhinitis.²²

Conclusion

The use of T. chebula in various traditional medical practices around the world is well established. There is ample evidence supporting multiple biologic properties of this Ayurvedic staple. While it is not a standard ingredient in dermatologic health care in the West, the data support continued research as to how best to incorporate this agent.

References

1. BMC Complement Altern Med. 2011 Oct 7;11:86.

2. Phytother Res. 2002 May;16(3):227-31.

3. Pharm Biol. 2010 Apr;48(4):469-81.

4. Pak J Biol Sci. 2007 Jul 1;10(13):2241-56.

5. BMC Complement Altern Med. 2010 May 13;10:20.

6. Int J Mol Med. 2011 Dec;28(6):1013-8.

7. Evid Based Complement Alternat Med. 2014;2014:701656.

8. Phytother Res. 2004 Sep;18:737-41.

9. Acta Pol Pharm. 2010 Mar-Apr;67(2):145-50.

10. Nat Prod Res. 2010 Dec;24(20):1915-26.

11. Pharm Biol. 2011 Nov;49(11):1190-203.

12. Pharm Biol. 2011 Jun;49(6):553-62.

13. Forsch Komplementmed. 2012;19(1):20-5.

14. Antiviral Res. 1995 May;27(1-2):19-37.

15. Chem Biodivers. 2013 Aug;10(8):1448-63.

16. Mycoses. 2014 Aug;57(8):497-506.

17. Phytother Res. 2005 Jul;19(7):582-6.

18. Chin J Integr Med. 2012 Dec;18(12):946-54.

19. J Surg Res. 2008 Jan;144(1):94-101.

20. J Surg Res. 2010 Jan;158(1):162-70.

21. J Altern Complement Med. 2010 Dec;16(12):1301-8.

22. Toxicol Mech Methods. 2005;15(3):193-204.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook, “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 people die as a result of these infections. To promote improved antibiotic-prescribing behaviors among the nation’s hospitalists, SHM launched its “Fight the Resistance” campaign in November 2015. Cynthia Cheung, MD, a hospitalist in the Triton Hospitalists group at Houston Methodist Willowbrook Hospital and assistant professor of clinical medicine at Houston Methodist, recently shared efforts by a team at her hospital that are closely aligned with SHM’s campaign.

Question: What led you to a career in hospital medicine?

Answer: I was very fortunate to train in a program that had excellent hospitalists at the University of California at Los Angeles. Our general wards were staffed by very talented attending physicians, many of whom were hospitalists, and I quickly fell in love with the fast pace of hospital medicine. My UCLA experience confirmed that hospital medicine was the path for me. I finished my residency in 2010 and began my current role at Houston Methodist early in 2014. Almost two years later, I still love what I do.

Q: How did you get involved in antibiotic stewardship at your hospital?

A: One of my colleagues, an infectious disease specialist and chair of our antimicrobial stewardship committee, invited me to join her team. In retrospect, I had never really thought very much about antibiotic stewardship aside from trying to prescribe the proper antibiotics and the appropriate dosages to my patients. I had not fully considered the quality perspective under such a focused lens; being a part of this committee really opened my eyes, especially since the committee’s goals are completely focused on optimizing clinical outcomes and minimizing unintended consequences of antibiotic use.

Q: What most excites you about SHM’s “Fight the Resistance” campaign?

A: I joined SHM a year ago, and I think it’s really exciting that SHM is drawing attention to hospitalists’ roles in promoting antibiotic stewardship in addition to its other quality improvement initiatives. Previously, antibiotic stewardship appeared to be mostly the province of infectious disease physicians, but that isn’t the case anymore. As frontline providers, we are poised to make a difference in appropriate antibiotic use if armed with the proper knowledge and tools.

Q: As part of “Fight the Resistance,” SHM developed recommendations for promoting antibiotic stewardship in hospitals. How do your team efforts align with SHM’s campaign?

A: One of SHM’s recommendations is to engage with a team of hospital-based clinicians to improve stewardship, and our committee oversees a pharmacist-driven real-time audit and feedback intervention to optimize antibiotic use. Often, after a provider places an antibiotic order, additional culture results and clinical information become available. Our pharmacists evaluate this information and contact the provider if they feel the antibiotic dose prescribed is not the most effective or if there is a culture-antibiotic mismatch.

Or the pharmacist might notice that a patient has been taking an antibiotic for an extended duration and may discuss with the provider whether an appropriate duration can be defined. They will call and consult with providers to help them consider discontinuation or de-escalation if necessary. This is in line with SHM’s recommendation to rethink antibiotic treatment time course. Our clinician acceptance rate has been 90 percent in favor of interventions proposed by the pharmacists.

Any time a provider declines pharmacist intervention, our committee reviews these cases to determine whether or not the decision was in the best interest of the patient given the information available. The reviewers include an interdisciplinary team of hospitalists, infectious disease physicians, critical care physicians, and emergency physicians. If one particular clinician has a record of prescribing suboptimally, the team would review that particular provider’s prescribing habits with more detail.

Our committee is also aligned with SHM’s recommendation to identify mechanisms to educate providers on appropriate prescribing by creating guidelines for different classes of bacterial infections and communicating them to our clinical staff. For gram-negative infections, we recommend avoiding the use of carbapenems and antipseudomonal agents in known pathogens that are not pseudonomous. For gram-positive infections, we advise against use of MRSA/VRE-active antibiotics in known pathogens that are not resistant and the use of double coverage in non-synergistic settings. In the case of anaerobic infections, our guidelines suggest clinicians not use double coverage when susceptibilities are known. These guidelines form the backbone of our reviews and assist the pharmacists in their feedback and audit.

Moving forward, one of our committee’s primary action items is to develop a method of communicating our resistance patterns effectively to our clinical staff to make them more widely known. The information is currently sitting in a silo and is not as easily accessible to assist clinicians in their decision-making process when prescribing antibiotics. We also hope to address appropriate usage of daptomycin and ceftaroline, reduce rates of inappropriate treatment of asymptomatic bacteriuria, and seek additional ways to reduce rates of Clostridium difficile infection.

Q: What do you think is most important for hospitalists to know about their roles in antibiotic stewardship?

A: It is extremely important to remember that antibiotics are one of the few classes of drugs that can harm a patient through promotion of resistance—even if the medication was not given to the patient directly. A lot of clinicians may have been taught a certain way to prescribe antibiotics in training or have become rooted in habit. Hospitalists need to proactively stay abreast of antibiotic stewardship developments, share with fellow providers, and not be afraid to alter the way they prescribe.

While this personal education process might seem daunting at first, medicine is a lifelong learning experience. As physicians, we see new things and learn new things every day. I encourage all hospitalists—and all hospital-based staff—to try to take a greater role in stewardship. You do not have to be a specialist to make a difference, and it doesn’t matter at which point in your career you are. Antibiotic resistance affects everyone. Now is the time to step up and fight it. TH

Brett Radler is SHM’s communications coordinator.

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 people die as a result of these infections. To promote improved antibiotic-prescribing behaviors among the nation’s hospitalists, SHM launched its “Fight the Resistance” campaign in November 2015. Cynthia Cheung, MD, a hospitalist in the Triton Hospitalists group at Houston Methodist Willowbrook Hospital and assistant professor of clinical medicine at Houston Methodist, recently shared efforts by a team at her hospital that are closely aligned with SHM’s campaign.

Question: What led you to a career in hospital medicine?

Answer: I was very fortunate to train in a program that had excellent hospitalists at the University of California at Los Angeles. Our general wards were staffed by very talented attending physicians, many of whom were hospitalists, and I quickly fell in love with the fast pace of hospital medicine. My UCLA experience confirmed that hospital medicine was the path for me. I finished my residency in 2010 and began my current role at Houston Methodist early in 2014. Almost two years later, I still love what I do.

Q: How did you get involved in antibiotic stewardship at your hospital?

A: One of my colleagues, an infectious disease specialist and chair of our antimicrobial stewardship committee, invited me to join her team. In retrospect, I had never really thought very much about antibiotic stewardship aside from trying to prescribe the proper antibiotics and the appropriate dosages to my patients. I had not fully considered the quality perspective under such a focused lens; being a part of this committee really opened my eyes, especially since the committee’s goals are completely focused on optimizing clinical outcomes and minimizing unintended consequences of antibiotic use.

Q: What most excites you about SHM’s “Fight the Resistance” campaign?

A: I joined SHM a year ago, and I think it’s really exciting that SHM is drawing attention to hospitalists’ roles in promoting antibiotic stewardship in addition to its other quality improvement initiatives. Previously, antibiotic stewardship appeared to be mostly the province of infectious disease physicians, but that isn’t the case anymore. As frontline providers, we are poised to make a difference in appropriate antibiotic use if armed with the proper knowledge and tools.

Q: As part of “Fight the Resistance,” SHM developed recommendations for promoting antibiotic stewardship in hospitals. How do your team efforts align with SHM’s campaign?

A: One of SHM’s recommendations is to engage with a team of hospital-based clinicians to improve stewardship, and our committee oversees a pharmacist-driven real-time audit and feedback intervention to optimize antibiotic use. Often, after a provider places an antibiotic order, additional culture results and clinical information become available. Our pharmacists evaluate this information and contact the provider if they feel the antibiotic dose prescribed is not the most effective or if there is a culture-antibiotic mismatch.

Or the pharmacist might notice that a patient has been taking an antibiotic for an extended duration and may discuss with the provider whether an appropriate duration can be defined. They will call and consult with providers to help them consider discontinuation or de-escalation if necessary. This is in line with SHM’s recommendation to rethink antibiotic treatment time course. Our clinician acceptance rate has been 90 percent in favor of interventions proposed by the pharmacists.

Any time a provider declines pharmacist intervention, our committee reviews these cases to determine whether or not the decision was in the best interest of the patient given the information available. The reviewers include an interdisciplinary team of hospitalists, infectious disease physicians, critical care physicians, and emergency physicians. If one particular clinician has a record of prescribing suboptimally, the team would review that particular provider’s prescribing habits with more detail.

Our committee is also aligned with SHM’s recommendation to identify mechanisms to educate providers on appropriate prescribing by creating guidelines for different classes of bacterial infections and communicating them to our clinical staff. For gram-negative infections, we recommend avoiding the use of carbapenems and antipseudomonal agents in known pathogens that are not pseudonomous. For gram-positive infections, we advise against use of MRSA/VRE-active antibiotics in known pathogens that are not resistant and the use of double coverage in non-synergistic settings. In the case of anaerobic infections, our guidelines suggest clinicians not use double coverage when susceptibilities are known. These guidelines form the backbone of our reviews and assist the pharmacists in their feedback and audit.

Moving forward, one of our committee’s primary action items is to develop a method of communicating our resistance patterns effectively to our clinical staff to make them more widely known. The information is currently sitting in a silo and is not as easily accessible to assist clinicians in their decision-making process when prescribing antibiotics. We also hope to address appropriate usage of daptomycin and ceftaroline, reduce rates of inappropriate treatment of asymptomatic bacteriuria, and seek additional ways to reduce rates of Clostridium difficile infection.

Q: What do you think is most important for hospitalists to know about their roles in antibiotic stewardship?

A: It is extremely important to remember that antibiotics are one of the few classes of drugs that can harm a patient through promotion of resistance—even if the medication was not given to the patient directly. A lot of clinicians may have been taught a certain way to prescribe antibiotics in training or have become rooted in habit. Hospitalists need to proactively stay abreast of antibiotic stewardship developments, share with fellow providers, and not be afraid to alter the way they prescribe.

While this personal education process might seem daunting at first, medicine is a lifelong learning experience. As physicians, we see new things and learn new things every day. I encourage all hospitalists—and all hospital-based staff—to try to take a greater role in stewardship. You do not have to be a specialist to make a difference, and it doesn’t matter at which point in your career you are. Antibiotic resistance affects everyone. Now is the time to step up and fight it. TH

Brett Radler is SHM’s communications coordinator.

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 people die as a result of these infections. To promote improved antibiotic-prescribing behaviors among the nation’s hospitalists, SHM launched its “Fight the Resistance” campaign in November 2015. Cynthia Cheung, MD, a hospitalist in the Triton Hospitalists group at Houston Methodist Willowbrook Hospital and assistant professor of clinical medicine at Houston Methodist, recently shared efforts by a team at her hospital that are closely aligned with SHM’s campaign.

Question: What led you to a career in hospital medicine?

Answer: I was very fortunate to train in a program that had excellent hospitalists at the University of California at Los Angeles. Our general wards were staffed by very talented attending physicians, many of whom were hospitalists, and I quickly fell in love with the fast pace of hospital medicine. My UCLA experience confirmed that hospital medicine was the path for me. I finished my residency in 2010 and began my current role at Houston Methodist early in 2014. Almost two years later, I still love what I do.

Q: How did you get involved in antibiotic stewardship at your hospital?

A: One of my colleagues, an infectious disease specialist and chair of our antimicrobial stewardship committee, invited me to join her team. In retrospect, I had never really thought very much about antibiotic stewardship aside from trying to prescribe the proper antibiotics and the appropriate dosages to my patients. I had not fully considered the quality perspective under such a focused lens; being a part of this committee really opened my eyes, especially since the committee’s goals are completely focused on optimizing clinical outcomes and minimizing unintended consequences of antibiotic use.

Q: What most excites you about SHM’s “Fight the Resistance” campaign?

A: I joined SHM a year ago, and I think it’s really exciting that SHM is drawing attention to hospitalists’ roles in promoting antibiotic stewardship in addition to its other quality improvement initiatives. Previously, antibiotic stewardship appeared to be mostly the province of infectious disease physicians, but that isn’t the case anymore. As frontline providers, we are poised to make a difference in appropriate antibiotic use if armed with the proper knowledge and tools.

Q: As part of “Fight the Resistance,” SHM developed recommendations for promoting antibiotic stewardship in hospitals. How do your team efforts align with SHM’s campaign?

A: One of SHM’s recommendations is to engage with a team of hospital-based clinicians to improve stewardship, and our committee oversees a pharmacist-driven real-time audit and feedback intervention to optimize antibiotic use. Often, after a provider places an antibiotic order, additional culture results and clinical information become available. Our pharmacists evaluate this information and contact the provider if they feel the antibiotic dose prescribed is not the most effective or if there is a culture-antibiotic mismatch.

Or the pharmacist might notice that a patient has been taking an antibiotic for an extended duration and may discuss with the provider whether an appropriate duration can be defined. They will call and consult with providers to help them consider discontinuation or de-escalation if necessary. This is in line with SHM’s recommendation to rethink antibiotic treatment time course. Our clinician acceptance rate has been 90 percent in favor of interventions proposed by the pharmacists.

Any time a provider declines pharmacist intervention, our committee reviews these cases to determine whether or not the decision was in the best interest of the patient given the information available. The reviewers include an interdisciplinary team of hospitalists, infectious disease physicians, critical care physicians, and emergency physicians. If one particular clinician has a record of prescribing suboptimally, the team would review that particular provider’s prescribing habits with more detail.

Our committee is also aligned with SHM’s recommendation to identify mechanisms to educate providers on appropriate prescribing by creating guidelines for different classes of bacterial infections and communicating them to our clinical staff. For gram-negative infections, we recommend avoiding the use of carbapenems and antipseudomonal agents in known pathogens that are not pseudonomous. For gram-positive infections, we advise against use of MRSA/VRE-active antibiotics in known pathogens that are not resistant and the use of double coverage in non-synergistic settings. In the case of anaerobic infections, our guidelines suggest clinicians not use double coverage when susceptibilities are known. These guidelines form the backbone of our reviews and assist the pharmacists in their feedback and audit.

Moving forward, one of our committee’s primary action items is to develop a method of communicating our resistance patterns effectively to our clinical staff to make them more widely known. The information is currently sitting in a silo and is not as easily accessible to assist clinicians in their decision-making process when prescribing antibiotics. We also hope to address appropriate usage of daptomycin and ceftaroline, reduce rates of inappropriate treatment of asymptomatic bacteriuria, and seek additional ways to reduce rates of Clostridium difficile infection.

Q: What do you think is most important for hospitalists to know about their roles in antibiotic stewardship?

A: It is extremely important to remember that antibiotics are one of the few classes of drugs that can harm a patient through promotion of resistance—even if the medication was not given to the patient directly. A lot of clinicians may have been taught a certain way to prescribe antibiotics in training or have become rooted in habit. Hospitalists need to proactively stay abreast of antibiotic stewardship developments, share with fellow providers, and not be afraid to alter the way they prescribe.

While this personal education process might seem daunting at first, medicine is a lifelong learning experience. As physicians, we see new things and learn new things every day. I encourage all hospitalists—and all hospital-based staff—to try to take a greater role in stewardship. You do not have to be a specialist to make a difference, and it doesn’t matter at which point in your career you are. Antibiotic resistance affects everyone. Now is the time to step up and fight it. TH

Brett Radler is SHM’s communications coordinator.

Patients seeking fertility care commonly ask the physician for advice regarding ways to optimize their conception attempts. While evidence from randomized controlled trials is not available, data from observational studies provide parameters that can inform patient decision making. Knowledge about the fertility window, the decline in fecundability with age, and lifestyle practices that promote conception may be helpful to clinicians and aid in their ability to guide patients.

For those patients who will not achieve conception naturally, assisted reproductive technologies (ART) offer a promising alternative. ART options have improved greatly in effectiveness and safety since Louise Brown was born in 1978. More than 5 million babies have been born globally.¹ However, even though the United States is wealthy, access to in vitro fertilization (IVF) is poor relative to many other countries, with not more than 1 in 3 people needing IVF actually receiving the treatment. Understanding the international experience enables physicians to take actions that help increase access for their patients who need IVF.

In this article we not only address ways in which your patients can optimize their natural fertility but also examine this country’s ability to offer ART options when they are needed. Without such examination, fundamental changes in societal attitudes toward infertility and payor attitudes toward reproductive care will not occur, and it is these changes, among others, that can move this country to more equitable ART access.

Increasing access to assisted reproductive technologies
Besides per capita income, the major factor affecting access to ART is the role of public funding of health care. However, effectiveness also matters. Globally, only 1 cycle in 5 results in a live birth.²³ In the United States, 1 in 3 cycles result in a live birth—even with a population of older patients than many other countries. For US patients aged 37 or younger, approximately 2 in 5 who undergo 1 ART cycle will have a baby.²³ However, these results also demonstrate that, even with the highest live-birth rates in the world, a large majority of US patients will require more than 1 cycle of IVF. Therefore, access remains critical to enable not only the first cycle but also more than 1 cycle to be attempted.

One of the reasons for the higher US pregnancy rate is that we, historically, have replaced more embryos than other countries. This is not the only, or even the major, reason for higher pregnancy rates; however, it is the major reason for a higher multiple pregnancy rate.

Physician and patient education programs to address this problem have resulted in fewer embryos being replaced, and a slight reduction in the multiple pregnancy rates, but much further progress is needed (FIGURE 1).²³

 

23

The crux of the problem: Competition for a positive result
Importantly, the major reason more embryos are replaced in the United States is that poorer access is related to a higher number of embryos replaced in order to try to get patients pregnant with fewer cycles. This pressure is created both by patients and by physicians—especially because the United States is one of the few countries that mandates the publication of clinic-specific pregnancy rates.

This government mandate changes clinical practice toward maximizing pregnancy rates because IVF clinics cannot afford, for competitive reasons, to have lower pregnancy rates than other clinics. This is unfortunate, because it has been shown that when elective single embryo transfer (eSET) is implemented, pregnancy rates do not decrease significantly but, in fact, multiple pregnancy rates drop dramatically (FIGURE 2).²³
 

 

23

The cost of IVF obviously impacts access, but the issue is more complex than it appears. IVF in the United States costs about 30% to 50% more than in other countries. But general US health care costs are also relatively even higher than that, and IVF is not expensive relative to other medical services.^24,25 Nevertheless, compared with other countries, the average US cost of a standard fresh IVF cycle is the highest as a percentage of gross national income per capita, at about 25%.²⁶ However, because of higher live birth rates, the cost-effectiveness of ART (which is the cost per live birth) in the United States is not unfavorable relative to other countries.²⁶

What matters to patients, however, is affordability, which is the net cost to patients after all subsidies relative to disposable income. US out-of-pocket costs for IVF as a percent of annual disposable income make IVF costs in the United States among the least affordable in the world. Affordability predicts utilization, as well as number of embryos transferred.²⁴ It is clear that less affordable IVF cycles result in more embryos being transferred. Broad insurance mandates result in large increases in treatment access but also significantly less aggressive treatment. More limited insurance mandates generally have little effect on IVF markets, which is why there is only a slight difference in practice behavior in mandated states because, nationally, coverage is poor (FIGURE 3).^24,27,28

 

28

We must increase access to ART by increasing funding
In summary, the economic factors that affect affordability are the cost of treatment, socioeconomic status, disposable income, government coverage, insurance coverage, and access to financing/loan programs. Access is affected by many factors, but only countries with funding arrangements that minimize out-of-pocket expenses meet expected demand of infertile patients. ART is expensive from a patient perspective, but not from a societal perspective. To increase subsidies we must:

 

• change societal attitudes toward infertility
• change payor attitudes toward reproductive care
• convince payers of cost-effectiveness
• develop effective payment plans and programs
• improve protocols (eg, eSET)
• educate patients and professionals
• use technology appropriately
• standardize treatments through research
• innovate new technologies to reduce costs
• develop patient criteria for inclusion in subsidization.

The ASRM has taken the lead in this respect in the United States by having an Access to Care Summit in September 2015, as well as an Advocacy Forum, and will continue to advocate for better coverage for infertility care. Internationally, FIGO (the International Federation of Gynecologyand Obstetrics) has taken the initiative to increase ART access, with the Committee on Reproductive Medicine distributing The FIGO Fertility Toolbox (http://www.fertilitytool.com).

World Health Organization Infertility Initiative
The World Health Organization (WHO) has, over the past 5 years, made a major initiative to increase global access to infertility diagnosis and treatment. This effort was effected through 3 major activities:

 

• rapid assessment task force
• reproductive medicine glossary
• fertility guidelines. 

The Rapid Assessment Task Force. This Task Force developed a comprehensive questionnaire for the 195 governments that belong to and adhere to WHO guidelines. This questionnaire, which is to be completed by government health departments, requires the government to document the breadth and depth of their infertility services and identify deficiencies or gaps. It is expected that the questionnaire will be distributed to all governments of the world in 2016, including the United States. The information that is received by the Task Force will be analyzed by the WHO to help develop plans for improved national infertility services globally.

The Reproductive Medicine glossary. This glossary being developed is a revision and major update of The International Committee Monitoring ART (ICMART)/WHO Glossary.²⁹ The number of definitions in the glossary is being increased 4-fold to about 300 definitions to include not only ART but also sections on clinical definitions, out‑comes, laboratory/embryology, epidemiology/public health, and andrology. While easy to overlook, definitions are essential to the accurate documentation of disease, communication among professionals, research comparisons, insurance coverage, billing and coding, and other issues.

For example, because the definition of infertility must include not only couples but also single persons, be flexible to deal with clinical versus epidemiologic and public health requirements, account for pre-existing conditions and age, and identify it as both a disease and a disability. Abortion definitions are complicated by the desire of many to call spontaneous abortion “miscarriage” and by the duration of pregnancy necessary before “delivery” of a fetus occurs. There is a desire to remove conception as a term (although it is widely used) because it is not a biological event. Pregnancy has its own complexities, including when it is initiated, which is now considered to be at the time of implantation. The glossary is expected to be published by mid-2016.

The WHO infertility guidelines. These have been an exhaustively-developed set of guidelines based on a comprehensive review and assessment of the entire literature by approximately 60 international experts working in teams with other assistants and experts using a standardized PICO (Population, Intervention, Comparators, and Outcomes of interest) system. This was a truly herculean effort. Guidelines are being finalized in the following areas: female infertility, unexplained infertility, polycystic ovary syndrome, ovarian stimulation, intrauterine insemination, ovarian hyperstimulation syndrome, IVF, and male infertility. After thorough review by the WHO, these guidelines will be published in hard copy and electronically in mid-2016.

Watch for access tools available this year
The plans are for the Task Force recommendations, the glossary, and the fertility guidelines, including The FIGO Fertility Toolbox to be presented as a comprehensive package to all of the governments of the world in 2016. This will give them the tools and encouragement to assess their fertility services and to use the WHO fertility package to improve access, effectiveness, and safety of infertility services in their respective countries.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Patients seeking fertility care commonly ask the physician for advice regarding ways to optimize their conception attempts. While evidence from randomized controlled trials is not available, data from observational studies provide parameters that can inform patient decision making. Knowledge about the fertility window, the decline in fecundability with age, and lifestyle practices that promote conception may be helpful to clinicians and aid in their ability to guide patients.

For those patients who will not achieve conception naturally, assisted reproductive technologies (ART) offer a promising alternative. ART options have improved greatly in effectiveness and safety since Louise Brown was born in 1978. More than 5 million babies have been born globally.¹ However, even though the United States is wealthy, access to in vitro fertilization (IVF) is poor relative to many other countries, with not more than 1 in 3 people needing IVF actually receiving the treatment. Understanding the international experience enables physicians to take actions that help increase access for their patients who need IVF.

In this article we not only address ways in which your patients can optimize their natural fertility but also examine this country’s ability to offer ART options when they are needed. Without such examination, fundamental changes in societal attitudes toward infertility and payor attitudes toward reproductive care will not occur, and it is these changes, among others, that can move this country to more equitable ART access.

Increasing access to assisted reproductive technologies
Besides per capita income, the major factor affecting access to ART is the role of public funding of health care. However, effectiveness also matters. Globally, only 1 cycle in 5 results in a live birth.²³ In the United States, 1 in 3 cycles result in a live birth—even with a population of older patients than many other countries. For US patients aged 37 or younger, approximately 2 in 5 who undergo 1 ART cycle will have a baby.²³ However, these results also demonstrate that, even with the highest live-birth rates in the world, a large majority of US patients will require more than 1 cycle of IVF. Therefore, access remains critical to enable not only the first cycle but also more than 1 cycle to be attempted.

One of the reasons for the higher US pregnancy rate is that we, historically, have replaced more embryos than other countries. This is not the only, or even the major, reason for higher pregnancy rates; however, it is the major reason for a higher multiple pregnancy rate.

Physician and patient education programs to address this problem have resulted in fewer embryos being replaced, and a slight reduction in the multiple pregnancy rates, but much further progress is needed (FIGURE 1).²³

 

23

The crux of the problem: Competition for a positive result
Importantly, the major reason more embryos are replaced in the United States is that poorer access is related to a higher number of embryos replaced in order to try to get patients pregnant with fewer cycles. This pressure is created both by patients and by physicians—especially because the United States is one of the few countries that mandates the publication of clinic-specific pregnancy rates.

This government mandate changes clinical practice toward maximizing pregnancy rates because IVF clinics cannot afford, for competitive reasons, to have lower pregnancy rates than other clinics. This is unfortunate, because it has been shown that when elective single embryo transfer (eSET) is implemented, pregnancy rates do not decrease significantly but, in fact, multiple pregnancy rates drop dramatically (FIGURE 2).²³
 

 

23

The cost of IVF obviously impacts access, but the issue is more complex than it appears. IVF in the United States costs about 30% to 50% more than in other countries. But general US health care costs are also relatively even higher than that, and IVF is not expensive relative to other medical services.^24,25 Nevertheless, compared with other countries, the average US cost of a standard fresh IVF cycle is the highest as a percentage of gross national income per capita, at about 25%.²⁶ However, because of higher live birth rates, the cost-effectiveness of ART (which is the cost per live birth) in the United States is not unfavorable relative to other countries.²⁶

What matters to patients, however, is affordability, which is the net cost to patients after all subsidies relative to disposable income. US out-of-pocket costs for IVF as a percent of annual disposable income make IVF costs in the United States among the least affordable in the world. Affordability predicts utilization, as well as number of embryos transferred.²⁴ It is clear that less affordable IVF cycles result in more embryos being transferred. Broad insurance mandates result in large increases in treatment access but also significantly less aggressive treatment. More limited insurance mandates generally have little effect on IVF markets, which is why there is only a slight difference in practice behavior in mandated states because, nationally, coverage is poor (FIGURE 3).^24,27,28

 

28

We must increase access to ART by increasing funding
In summary, the economic factors that affect affordability are the cost of treatment, socioeconomic status, disposable income, government coverage, insurance coverage, and access to financing/loan programs. Access is affected by many factors, but only countries with funding arrangements that minimize out-of-pocket expenses meet expected demand of infertile patients. ART is expensive from a patient perspective, but not from a societal perspective. To increase subsidies we must:

 

• change societal attitudes toward infertility
• change payor attitudes toward reproductive care
• convince payers of cost-effectiveness
• develop effective payment plans and programs
• improve protocols (eg, eSET)
• educate patients and professionals
• use technology appropriately
• standardize treatments through research
• innovate new technologies to reduce costs
• develop patient criteria for inclusion in subsidization.

The ASRM has taken the lead in this respect in the United States by having an Access to Care Summit in September 2015, as well as an Advocacy Forum, and will continue to advocate for better coverage for infertility care. Internationally, FIGO (the International Federation of Gynecologyand Obstetrics) has taken the initiative to increase ART access, with the Committee on Reproductive Medicine distributing The FIGO Fertility Toolbox (http://www.fertilitytool.com).

World Health Organization Infertility Initiative
The World Health Organization (WHO) has, over the past 5 years, made a major initiative to increase global access to infertility diagnosis and treatment. This effort was effected through 3 major activities:

 

• rapid assessment task force
• reproductive medicine glossary
• fertility guidelines. 

The Rapid Assessment Task Force. This Task Force developed a comprehensive questionnaire for the 195 governments that belong to and adhere to WHO guidelines. This questionnaire, which is to be completed by government health departments, requires the government to document the breadth and depth of their infertility services and identify deficiencies or gaps. It is expected that the questionnaire will be distributed to all governments of the world in 2016, including the United States. The information that is received by the Task Force will be analyzed by the WHO to help develop plans for improved national infertility services globally.

The Reproductive Medicine glossary. This glossary being developed is a revision and major update of The International Committee Monitoring ART (ICMART)/WHO Glossary.²⁹ The number of definitions in the glossary is being increased 4-fold to about 300 definitions to include not only ART but also sections on clinical definitions, out‑comes, laboratory/embryology, epidemiology/public health, and andrology. While easy to overlook, definitions are essential to the accurate documentation of disease, communication among professionals, research comparisons, insurance coverage, billing and coding, and other issues.

For example, because the definition of infertility must include not only couples but also single persons, be flexible to deal with clinical versus epidemiologic and public health requirements, account for pre-existing conditions and age, and identify it as both a disease and a disability. Abortion definitions are complicated by the desire of many to call spontaneous abortion “miscarriage” and by the duration of pregnancy necessary before “delivery” of a fetus occurs. There is a desire to remove conception as a term (although it is widely used) because it is not a biological event. Pregnancy has its own complexities, including when it is initiated, which is now considered to be at the time of implantation. The glossary is expected to be published by mid-2016.

The WHO infertility guidelines. These have been an exhaustively-developed set of guidelines based on a comprehensive review and assessment of the entire literature by approximately 60 international experts working in teams with other assistants and experts using a standardized PICO (Population, Intervention, Comparators, and Outcomes of interest) system. This was a truly herculean effort. Guidelines are being finalized in the following areas: female infertility, unexplained infertility, polycystic ovary syndrome, ovarian stimulation, intrauterine insemination, ovarian hyperstimulation syndrome, IVF, and male infertility. After thorough review by the WHO, these guidelines will be published in hard copy and electronically in mid-2016.

Watch for access tools available this year
The plans are for the Task Force recommendations, the glossary, and the fertility guidelines, including The FIGO Fertility Toolbox to be presented as a comprehensive package to all of the governments of the world in 2016. This will give them the tools and encouragement to assess their fertility services and to use the WHO fertility package to improve access, effectiveness, and safety of infertility services in their respective countries.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Patients seeking fertility care commonly ask the physician for advice regarding ways to optimize their conception attempts. While evidence from randomized controlled trials is not available, data from observational studies provide parameters that can inform patient decision making. Knowledge about the fertility window, the decline in fecundability with age, and lifestyle practices that promote conception may be helpful to clinicians and aid in their ability to guide patients.

For those patients who will not achieve conception naturally, assisted reproductive technologies (ART) offer a promising alternative. ART options have improved greatly in effectiveness and safety since Louise Brown was born in 1978. More than 5 million babies have been born globally.¹ However, even though the United States is wealthy, access to in vitro fertilization (IVF) is poor relative to many other countries, with not more than 1 in 3 people needing IVF actually receiving the treatment. Understanding the international experience enables physicians to take actions that help increase access for their patients who need IVF.

In this article we not only address ways in which your patients can optimize their natural fertility but also examine this country’s ability to offer ART options when they are needed. Without such examination, fundamental changes in societal attitudes toward infertility and payor attitudes toward reproductive care will not occur, and it is these changes, among others, that can move this country to more equitable ART access.

Increasing access to assisted reproductive technologies
Besides per capita income, the major factor affecting access to ART is the role of public funding of health care. However, effectiveness also matters. Globally, only 1 cycle in 5 results in a live birth.²³ In the United States, 1 in 3 cycles result in a live birth—even with a population of older patients than many other countries. For US patients aged 37 or younger, approximately 2 in 5 who undergo 1 ART cycle will have a baby.²³ However, these results also demonstrate that, even with the highest live-birth rates in the world, a large majority of US patients will require more than 1 cycle of IVF. Therefore, access remains critical to enable not only the first cycle but also more than 1 cycle to be attempted.

One of the reasons for the higher US pregnancy rate is that we, historically, have replaced more embryos than other countries. This is not the only, or even the major, reason for higher pregnancy rates; however, it is the major reason for a higher multiple pregnancy rate.

Physician and patient education programs to address this problem have resulted in fewer embryos being replaced, and a slight reduction in the multiple pregnancy rates, but much further progress is needed (FIGURE 1).²³

 

23

The crux of the problem: Competition for a positive result
Importantly, the major reason more embryos are replaced in the United States is that poorer access is related to a higher number of embryos replaced in order to try to get patients pregnant with fewer cycles. This pressure is created both by patients and by physicians—especially because the United States is one of the few countries that mandates the publication of clinic-specific pregnancy rates.

This government mandate changes clinical practice toward maximizing pregnancy rates because IVF clinics cannot afford, for competitive reasons, to have lower pregnancy rates than other clinics. This is unfortunate, because it has been shown that when elective single embryo transfer (eSET) is implemented, pregnancy rates do not decrease significantly but, in fact, multiple pregnancy rates drop dramatically (FIGURE 2).²³
 

 

23

The cost of IVF obviously impacts access, but the issue is more complex than it appears. IVF in the United States costs about 30% to 50% more than in other countries. But general US health care costs are also relatively even higher than that, and IVF is not expensive relative to other medical services.^24,25 Nevertheless, compared with other countries, the average US cost of a standard fresh IVF cycle is the highest as a percentage of gross national income per capita, at about 25%.²⁶ However, because of higher live birth rates, the cost-effectiveness of ART (which is the cost per live birth) in the United States is not unfavorable relative to other countries.²⁶

What matters to patients, however, is affordability, which is the net cost to patients after all subsidies relative to disposable income. US out-of-pocket costs for IVF as a percent of annual disposable income make IVF costs in the United States among the least affordable in the world. Affordability predicts utilization, as well as number of embryos transferred.²⁴ It is clear that less affordable IVF cycles result in more embryos being transferred. Broad insurance mandates result in large increases in treatment access but also significantly less aggressive treatment. More limited insurance mandates generally have little effect on IVF markets, which is why there is only a slight difference in practice behavior in mandated states because, nationally, coverage is poor (FIGURE 3).^24,27,28

 

28

We must increase access to ART by increasing funding
In summary, the economic factors that affect affordability are the cost of treatment, socioeconomic status, disposable income, government coverage, insurance coverage, and access to financing/loan programs. Access is affected by many factors, but only countries with funding arrangements that minimize out-of-pocket expenses meet expected demand of infertile patients. ART is expensive from a patient perspective, but not from a societal perspective. To increase subsidies we must:

 

• change societal attitudes toward infertility
• change payor attitudes toward reproductive care
• convince payers of cost-effectiveness
• develop effective payment plans and programs
• improve protocols (eg, eSET)
• educate patients and professionals
• use technology appropriately
• standardize treatments through research
• innovate new technologies to reduce costs
• develop patient criteria for inclusion in subsidization.

The ASRM has taken the lead in this respect in the United States by having an Access to Care Summit in September 2015, as well as an Advocacy Forum, and will continue to advocate for better coverage for infertility care. Internationally, FIGO (the International Federation of Gynecologyand Obstetrics) has taken the initiative to increase ART access, with the Committee on Reproductive Medicine distributing The FIGO Fertility Toolbox (http://www.fertilitytool.com).

World Health Organization Infertility Initiative
The World Health Organization (WHO) has, over the past 5 years, made a major initiative to increase global access to infertility diagnosis and treatment. This effort was effected through 3 major activities:

 

• rapid assessment task force
• reproductive medicine glossary
• fertility guidelines. 

The Rapid Assessment Task Force. This Task Force developed a comprehensive questionnaire for the 195 governments that belong to and adhere to WHO guidelines. This questionnaire, which is to be completed by government health departments, requires the government to document the breadth and depth of their infertility services and identify deficiencies or gaps. It is expected that the questionnaire will be distributed to all governments of the world in 2016, including the United States. The information that is received by the Task Force will be analyzed by the WHO to help develop plans for improved national infertility services globally.

The Reproductive Medicine glossary. This glossary being developed is a revision and major update of The International Committee Monitoring ART (ICMART)/WHO Glossary.²⁹ The number of definitions in the glossary is being increased 4-fold to about 300 definitions to include not only ART but also sections on clinical definitions, out‑comes, laboratory/embryology, epidemiology/public health, and andrology. While easy to overlook, definitions are essential to the accurate documentation of disease, communication among professionals, research comparisons, insurance coverage, billing and coding, and other issues.

For example, because the definition of infertility must include not only couples but also single persons, be flexible to deal with clinical versus epidemiologic and public health requirements, account for pre-existing conditions and age, and identify it as both a disease and a disability. Abortion definitions are complicated by the desire of many to call spontaneous abortion “miscarriage” and by the duration of pregnancy necessary before “delivery” of a fetus occurs. There is a desire to remove conception as a term (although it is widely used) because it is not a biological event. Pregnancy has its own complexities, including when it is initiated, which is now considered to be at the time of implantation. The glossary is expected to be published by mid-2016.

The WHO infertility guidelines. These have been an exhaustively-developed set of guidelines based on a comprehensive review and assessment of the entire literature by approximately 60 international experts working in teams with other assistants and experts using a standardized PICO (Population, Intervention, Comparators, and Outcomes of interest) system. This was a truly herculean effort. Guidelines are being finalized in the following areas: female infertility, unexplained infertility, polycystic ovary syndrome, ovarian stimulation, intrauterine insemination, ovarian hyperstimulation syndrome, IVF, and male infertility. After thorough review by the WHO, these guidelines will be published in hard copy and electronically in mid-2016.

Watch for access tools available this year
The plans are for the Task Force recommendations, the glossary, and the fertility guidelines, including The FIGO Fertility Toolbox to be presented as a comprehensive package to all of the governments of the world in 2016. This will give them the tools and encouragement to assess their fertility services and to use the WHO fertility package to improve access, effectiveness, and safety of infertility services in their respective countries.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.

In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.

“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”

Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.

“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.

In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.

The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.

In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.

Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.

“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.

“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.

Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.

Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.

NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.

In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.

“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”

Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.

“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.

In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.

The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.

In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.

Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.

“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.

“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.

Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.

Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.

NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.

In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.

“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”

Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.

“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.

In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.

The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.

In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.

Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.

“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.

“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.

Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.

Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.