There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

[email protected]

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

[email protected]

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

[email protected]

MIAMI—The possibility that Parkinson’s disease is a prion disorder has led investigators to begin clinical trials of drugs that target misfolded α-synuclein, according to an overview provided at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Other potential therapies targeting the protein are in preclinical studies.

Researchers are exploring four main treatment approaches: immunization, enhancing protein clearance, knocking down host α-synuclein, and inhibiting the prion conformer reaction, said C. Warren Olanow, MD, Professor and Chairman Emeritus of the Department of Neurology and Professor Emeritus of Neuroscience at the Mount Sinai School of Medicine in New York City.

Inhibiting the prion conformer reaction is the approach that Dr. Olanow believes is most likely to be effective. “But I also strongly believe every one of these approaches needs to be tested,” he said.

The Prion Hypothesis

A prion is an infectious particle composed solely of misfolded protein. It replicates by a process whereby the misfolded protein causes the native unfolded protein to misfold through a process called the prion conformer reaction. Misfolded proteins form beta-rich sheets that contain oligomers and rods, which are thought to be toxic, and polymerize to form aggregates. Prions can cause neurodegeneration and be transmitted from one species to another.

Researchers “have shown that α-synuclein can … replicate the prion biology,” and there are many reasons to suspect that α-synuclein “is integral to the pathology” of Parkinson’s disease, Dr. Olanow said. For instance, mutations as well as excess levels of wild type α-synuclein can cause Parkinson’s disease.

An α-synuclein monomer can misfold for various reasons, including a genetic mutation, a toxic or inflammatory event, or sporadically by chance. “As you get older, more and more proteins spontaneously misfold,” Dr. Olanow said.

The ubiquitin–proteasome and the autophagy–lysosomal systems normally clear misfolded proteins. If these systems cannot adequately clear the misfolded proteins—either because the clearance systems are not working enough or too much protein is being formed—the aggregates accumulate and can block the clearance systems, creating a vicious cycle that leads to further accumulation of misfolded α-synuclein, he said.

Removing Toxic Protein

One therapeutic approach based on the prion hypothesis involves targeting and removing toxic α-synuclein species by way of active or passive immunization.

Tran et al reported that α-synuclein immunotherapy blocks propagation of misfolded α-synuclein and neurodegeneration in an animal model. Several immune therapies are currently being tested in clinical trials. Trials by Prothena and Biogen are using passive immunization (ie, administering monoclonal antibodies targeted to a specific α-synuclein species), whereas trials by AFFiRiS are using active immunization (ie, stimulating the immune system to produce antibodies). “The good news so far is that there has been no major safety issue or tolerability concern,” Dr. Olanow said. “There have not, however, been long-term safety or efficacy data as yet.”

Challenges in immunization trials include uncertainty about whether antibodies reach the brain and which α-synuclein species should be targeted. Some α-synuclein species may be protective, said Dr. Olanow. “By no means are we assured that we are targeting exactly what we want.”

Enhancing Protein Clearance

Another approach entails facilitating protein clearance through the ubiquitin–proteasome system or the autophagy–lysosomal system, which are defective in Parkinson’s disease. Drugs that activate or enhance glucocerebrosidase (GCase) activity and promote lysosomal function have attracted particular attention.

Mutations in GBA, the gene that encodes for GCase, can cause Gaucher disease with features of parkinsonism, and as many as 10% of patients with Parkinson’s disease have GBA mutations. GCase levels are reduced by as much as 50% in patients with Parkinson’s disease.

When GCase is decreased, lysosomal function is reduced, and α-synuclein consequently increases. Likewise, overexpression of GCase can reduce α-synuclein, and overexpression of α-synuclein reduces GCase. Ambroxol, a molecular chaperone that has been shown experimentally to increase GCase levels, has entered clinical trials. More robust GCase-promoting agents are in development and will enter clinical trials in the near future, Dr. Olanow said.

Removing Host Protein

A third approach involves knockdown of host α-synuclein with, for example, iRNAs and antisense oligonucleotides directed at α-synuclein production or with chemicals that bind to α-synuclein. “If you knock down host α-synuclein, then you do not have any to participate in that prion conformer reaction,” he said.

Investigators are using high-throughput screening to identify chemicals that bind to α-synuclein. However, α-synuclein’s physiologic role is not completely known, nor is what happens if the protein is lowered in humans, or by how much α-synuclein would need to be reduced to provide benefit.

Blocking the Prion Conformer Reaction

If neurologists could block the prion conformer reaction, it might be the best approach. “We could stop the formation of misfolded protein, and we could preserve the host α-synuclein and its physiologic function,” Dr. Olanow said. “The problem is that we do not know the precise mechanism underlying the presumed templating in Parkinson’s disease.”

Any attempts to treat Parkinson’s disease with therapies aimed at α-synuclein likely should be initiated as early as possible in the disease process, and biomarkers will be crucial to initiating timely treatment, Dr. Olanow noted.

“This, to me, is one of the most exciting periods in Parkinson’s therapeutics,” he said. Over the next decade, neurologists may see “a revolution of therapies directed at α-synuclein that may ultimately prove to be disease modifying and fundamentally change the nature of the disease.”

—Jake Remaly

Suggested Reading

Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855-866.

Olanow CW, Kordower JH. Targeting α-synuclein as a therapy for Parkinson’s disease: The battle begins. Mov Disord. 2017;32(2):203-207.

Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.

Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211-218.

Tran HT, Chung CH, Iba M, et al. α-synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep. 2014;7(6):2054-2065.

MIAMI—The possibility that Parkinson’s disease is a prion disorder has led investigators to begin clinical trials of drugs that target misfolded α-synuclein, according to an overview provided at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Other potential therapies targeting the protein are in preclinical studies.

Researchers are exploring four main treatment approaches: immunization, enhancing protein clearance, knocking down host α-synuclein, and inhibiting the prion conformer reaction, said C. Warren Olanow, MD, Professor and Chairman Emeritus of the Department of Neurology and Professor Emeritus of Neuroscience at the Mount Sinai School of Medicine in New York City.

Inhibiting the prion conformer reaction is the approach that Dr. Olanow believes is most likely to be effective. “But I also strongly believe every one of these approaches needs to be tested,” he said.

The Prion Hypothesis

A prion is an infectious particle composed solely of misfolded protein. It replicates by a process whereby the misfolded protein causes the native unfolded protein to misfold through a process called the prion conformer reaction. Misfolded proteins form beta-rich sheets that contain oligomers and rods, which are thought to be toxic, and polymerize to form aggregates. Prions can cause neurodegeneration and be transmitted from one species to another.

Researchers “have shown that α-synuclein can … replicate the prion biology,” and there are many reasons to suspect that α-synuclein “is integral to the pathology” of Parkinson’s disease, Dr. Olanow said. For instance, mutations as well as excess levels of wild type α-synuclein can cause Parkinson’s disease.

An α-synuclein monomer can misfold for various reasons, including a genetic mutation, a toxic or inflammatory event, or sporadically by chance. “As you get older, more and more proteins spontaneously misfold,” Dr. Olanow said.

The ubiquitin–proteasome and the autophagy–lysosomal systems normally clear misfolded proteins. If these systems cannot adequately clear the misfolded proteins—either because the clearance systems are not working enough or too much protein is being formed—the aggregates accumulate and can block the clearance systems, creating a vicious cycle that leads to further accumulation of misfolded α-synuclein, he said.

Removing Toxic Protein

One therapeutic approach based on the prion hypothesis involves targeting and removing toxic α-synuclein species by way of active or passive immunization.

Tran et al reported that α-synuclein immunotherapy blocks propagation of misfolded α-synuclein and neurodegeneration in an animal model. Several immune therapies are currently being tested in clinical trials. Trials by Prothena and Biogen are using passive immunization (ie, administering monoclonal antibodies targeted to a specific α-synuclein species), whereas trials by AFFiRiS are using active immunization (ie, stimulating the immune system to produce antibodies). “The good news so far is that there has been no major safety issue or tolerability concern,” Dr. Olanow said. “There have not, however, been long-term safety or efficacy data as yet.”

Challenges in immunization trials include uncertainty about whether antibodies reach the brain and which α-synuclein species should be targeted. Some α-synuclein species may be protective, said Dr. Olanow. “By no means are we assured that we are targeting exactly what we want.”

Enhancing Protein Clearance

Another approach entails facilitating protein clearance through the ubiquitin–proteasome system or the autophagy–lysosomal system, which are defective in Parkinson’s disease. Drugs that activate or enhance glucocerebrosidase (GCase) activity and promote lysosomal function have attracted particular attention.

Mutations in GBA, the gene that encodes for GCase, can cause Gaucher disease with features of parkinsonism, and as many as 10% of patients with Parkinson’s disease have GBA mutations. GCase levels are reduced by as much as 50% in patients with Parkinson’s disease.

When GCase is decreased, lysosomal function is reduced, and α-synuclein consequently increases. Likewise, overexpression of GCase can reduce α-synuclein, and overexpression of α-synuclein reduces GCase. Ambroxol, a molecular chaperone that has been shown experimentally to increase GCase levels, has entered clinical trials. More robust GCase-promoting agents are in development and will enter clinical trials in the near future, Dr. Olanow said.

Removing Host Protein

A third approach involves knockdown of host α-synuclein with, for example, iRNAs and antisense oligonucleotides directed at α-synuclein production or with chemicals that bind to α-synuclein. “If you knock down host α-synuclein, then you do not have any to participate in that prion conformer reaction,” he said.

Investigators are using high-throughput screening to identify chemicals that bind to α-synuclein. However, α-synuclein’s physiologic role is not completely known, nor is what happens if the protein is lowered in humans, or by how much α-synuclein would need to be reduced to provide benefit.

Blocking the Prion Conformer Reaction

If neurologists could block the prion conformer reaction, it might be the best approach. “We could stop the formation of misfolded protein, and we could preserve the host α-synuclein and its physiologic function,” Dr. Olanow said. “The problem is that we do not know the precise mechanism underlying the presumed templating in Parkinson’s disease.”

Any attempts to treat Parkinson’s disease with therapies aimed at α-synuclein likely should be initiated as early as possible in the disease process, and biomarkers will be crucial to initiating timely treatment, Dr. Olanow noted.

“This, to me, is one of the most exciting periods in Parkinson’s therapeutics,” he said. Over the next decade, neurologists may see “a revolution of therapies directed at α-synuclein that may ultimately prove to be disease modifying and fundamentally change the nature of the disease.”

—Jake Remaly

Suggested Reading

Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855-866.

Olanow CW, Kordower JH. Targeting α-synuclein as a therapy for Parkinson’s disease: The battle begins. Mov Disord. 2017;32(2):203-207.

Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.

Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211-218.

Tran HT, Chung CH, Iba M, et al. α-synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep. 2014;7(6):2054-2065.

MIAMI—The possibility that Parkinson’s disease is a prion disorder has led investigators to begin clinical trials of drugs that target misfolded α-synuclein, according to an overview provided at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Other potential therapies targeting the protein are in preclinical studies.

Researchers are exploring four main treatment approaches: immunization, enhancing protein clearance, knocking down host α-synuclein, and inhibiting the prion conformer reaction, said C. Warren Olanow, MD, Professor and Chairman Emeritus of the Department of Neurology and Professor Emeritus of Neuroscience at the Mount Sinai School of Medicine in New York City.

Inhibiting the prion conformer reaction is the approach that Dr. Olanow believes is most likely to be effective. “But I also strongly believe every one of these approaches needs to be tested,” he said.

The Prion Hypothesis

A prion is an infectious particle composed solely of misfolded protein. It replicates by a process whereby the misfolded protein causes the native unfolded protein to misfold through a process called the prion conformer reaction. Misfolded proteins form beta-rich sheets that contain oligomers and rods, which are thought to be toxic, and polymerize to form aggregates. Prions can cause neurodegeneration and be transmitted from one species to another.

Researchers “have shown that α-synuclein can … replicate the prion biology,” and there are many reasons to suspect that α-synuclein “is integral to the pathology” of Parkinson’s disease, Dr. Olanow said. For instance, mutations as well as excess levels of wild type α-synuclein can cause Parkinson’s disease.

An α-synuclein monomer can misfold for various reasons, including a genetic mutation, a toxic or inflammatory event, or sporadically by chance. “As you get older, more and more proteins spontaneously misfold,” Dr. Olanow said.

The ubiquitin–proteasome and the autophagy–lysosomal systems normally clear misfolded proteins. If these systems cannot adequately clear the misfolded proteins—either because the clearance systems are not working enough or too much protein is being formed—the aggregates accumulate and can block the clearance systems, creating a vicious cycle that leads to further accumulation of misfolded α-synuclein, he said.

Removing Toxic Protein

One therapeutic approach based on the prion hypothesis involves targeting and removing toxic α-synuclein species by way of active or passive immunization.

Tran et al reported that α-synuclein immunotherapy blocks propagation of misfolded α-synuclein and neurodegeneration in an animal model. Several immune therapies are currently being tested in clinical trials. Trials by Prothena and Biogen are using passive immunization (ie, administering monoclonal antibodies targeted to a specific α-synuclein species), whereas trials by AFFiRiS are using active immunization (ie, stimulating the immune system to produce antibodies). “The good news so far is that there has been no major safety issue or tolerability concern,” Dr. Olanow said. “There have not, however, been long-term safety or efficacy data as yet.”

Challenges in immunization trials include uncertainty about whether antibodies reach the brain and which α-synuclein species should be targeted. Some α-synuclein species may be protective, said Dr. Olanow. “By no means are we assured that we are targeting exactly what we want.”

Enhancing Protein Clearance

Another approach entails facilitating protein clearance through the ubiquitin–proteasome system or the autophagy–lysosomal system, which are defective in Parkinson’s disease. Drugs that activate or enhance glucocerebrosidase (GCase) activity and promote lysosomal function have attracted particular attention.

Mutations in GBA, the gene that encodes for GCase, can cause Gaucher disease with features of parkinsonism, and as many as 10% of patients with Parkinson’s disease have GBA mutations. GCase levels are reduced by as much as 50% in patients with Parkinson’s disease.

When GCase is decreased, lysosomal function is reduced, and α-synuclein consequently increases. Likewise, overexpression of GCase can reduce α-synuclein, and overexpression of α-synuclein reduces GCase. Ambroxol, a molecular chaperone that has been shown experimentally to increase GCase levels, has entered clinical trials. More robust GCase-promoting agents are in development and will enter clinical trials in the near future, Dr. Olanow said.

Removing Host Protein

A third approach involves knockdown of host α-synuclein with, for example, iRNAs and antisense oligonucleotides directed at α-synuclein production or with chemicals that bind to α-synuclein. “If you knock down host α-synuclein, then you do not have any to participate in that prion conformer reaction,” he said.

Investigators are using high-throughput screening to identify chemicals that bind to α-synuclein. However, α-synuclein’s physiologic role is not completely known, nor is what happens if the protein is lowered in humans, or by how much α-synuclein would need to be reduced to provide benefit.

Blocking the Prion Conformer Reaction

If neurologists could block the prion conformer reaction, it might be the best approach. “We could stop the formation of misfolded protein, and we could preserve the host α-synuclein and its physiologic function,” Dr. Olanow said. “The problem is that we do not know the precise mechanism underlying the presumed templating in Parkinson’s disease.”

Any attempts to treat Parkinson’s disease with therapies aimed at α-synuclein likely should be initiated as early as possible in the disease process, and biomarkers will be crucial to initiating timely treatment, Dr. Olanow noted.

“This, to me, is one of the most exciting periods in Parkinson’s therapeutics,” he said. Over the next decade, neurologists may see “a revolution of therapies directed at α-synuclein that may ultimately prove to be disease modifying and fundamentally change the nature of the disease.”

—Jake Remaly

Suggested Reading

Dehay B, Bourdenx M, Gorry P, et al. Targeting α-synuclein for treating Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 2015;14(8):855-866.

Olanow CW, Kordower JH. Targeting α-synuclein as a therapy for Parkinson’s disease: The battle begins. Mov Disord. 2017;32(2):203-207.

Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.

Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211-218.

Tran HT, Chung CH, Iba M, et al. α-synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep. 2014;7(6):2054-2065.

WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.

These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.

Bruce Jancin/Frontline Medical News

[email protected]


 

WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.

These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.

Bruce Jancin/Frontline Medical News

[email protected]


 

WASHINGTON – In a large population of Medicare patients hospitalized for acute MI, four factors stood out as predictors of increased likelihood of readmission within 90 days, Aaron D. Kugelmass, MD, reported at the annual meeting of the American College of Cardiology.

These four predictors of 90-day readmission were end-stage renal disease at the time of the initial admission for MI, which in a logistic regression model was independently associated with an 88% relative increase in readmission risk; no percutaneous coronary intervention (PCI) during the index hospitalization, which carried a 64% increase in risk; type 1 diabetes, with a 57% increased readmission rate; and heart failure at the initial hospitalization, with an associated 34% greater risk, according to Dr. Kugelmass, chief of cardiology and medical director of the heart and vascular center at Baystate Medical Center in Springfield, Mass.

Bruce Jancin/Frontline Medical News

[email protected]


 

ORLANDO – Prolonged time spent sitting was associated with higher post–glucose tolerance test blood glucose levels among less-active women with polycystic ovary syndrome (PCOS).

The trend toward this effect persisted even after researchers controlled for age and body mass index, and was not seen in women who were more active.

The results showed a “compounded adverse metabolic effect of prolonged sitting time in women with PCOS who do not achieve exercise goals,” according to Eleni Greenwood, MD, and her colleagues at the University of California, San Francisco, department of obstetrics, gynecology, and reproductive sciences.

[email protected]

On Twitter @karioakes

ORLANDO – Prolonged time spent sitting was associated with higher post–glucose tolerance test blood glucose levels among less-active women with polycystic ovary syndrome (PCOS).

The trend toward this effect persisted even after researchers controlled for age and body mass index, and was not seen in women who were more active.

The results showed a “compounded adverse metabolic effect of prolonged sitting time in women with PCOS who do not achieve exercise goals,” according to Eleni Greenwood, MD, and her colleagues at the University of California, San Francisco, department of obstetrics, gynecology, and reproductive sciences.

[email protected]

On Twitter @karioakes

ORLANDO – Prolonged time spent sitting was associated with higher post–glucose tolerance test blood glucose levels among less-active women with polycystic ovary syndrome (PCOS).

The trend toward this effect persisted even after researchers controlled for age and body mass index, and was not seen in women who were more active.

The results showed a “compounded adverse metabolic effect of prolonged sitting time in women with PCOS who do not achieve exercise goals,” according to Eleni Greenwood, MD, and her colleagues at the University of California, San Francisco, department of obstetrics, gynecology, and reproductive sciences.

[email protected]

On Twitter @karioakes

Blepharoplasty, or surgical manipulation of the upper and/or lower eyelids, is a commonly performed cosmetic procedure to improve the appearance and function of the eyelids by repositioning and/or removing excess skin and soft tissue from the eyelids, most often through external incisions that minimize scarring and maximize the aesthetic outcomes of the surgery. Therefore, the placement of the incisions is an important determinant of the surgical outcome, and the preoperative marking of the eyelids to indicate where the incisions should be placed is a crucial part of preparation for the surgery.

Preoperative marking has unique challenges due to the dynamicity of the eyelids and the delicate nature of the surgery. The mark must be narrow to minimize the risk of placing the incision higher or lower than intended. The mark also must dry quickly because the patient may blink and create multiple impressions of the marking on skinfolds in contact with the wet ink. Fast drying of the ink used to create the marks improves the efficiency and clarity of the presurgical planning.

We present data on the performance of the various blepharoplasty markers regarding drying time and ink spread width based on an evaluation of 13 surgical markers.

Methods

Eleven unique fine tip (FT) markers and 2 standard tip (ST) markers were obtained based on their accessibility at the researchers’ home institution and availability for direct purchase in small quantities from the distributors (Figure 1). Four markers were double tipped with one FT end and one ST end; for these markers, only the FT end was studied. The experiments were conducted on the bilateral upper eyelids and on hairless patches of skin of a single patient in a minor procedure room with surgical lighting and minimal draft of air. The sole experimenter (J.M.K.) conducting the study was not blinded.

The drying time of each marker was measured by marking 1-in lines on a patch of hairless skin that was first cleaned with an alcohol pad, then dried. Drying time for each marking was measured in increments of 5 seconds; at each time point, the markings were wiped with a single-ply, light-duty tissue under the weight of 10 US quarters to ensure that the same weight/pressure was applied when wiping the skin. Smudges observed with the naked eye on either the wipe or the patients’ skin were interpreted as nondry status of the marking. The first time point at which a marking was found to have no visible smudges either on the skin or the wipe was recorded as the drying time of the respective marker.

Ink spread was measured on clean eyelid skin by drawing curved lines along the natural crease as would be done for actual blepharoplasty planning. Each line was allowed to dry for 2 minutes. The greatest perpendicular spread width along the line observed with the naked eye was measured using a digital Vernier caliper with 0.01-mm graduations. Three measurements were obtained per marker and the values averaged to arrive at the final spread width.

Results

Drying time among the 13 total markers (11 FT and 2 ST) ranged from 5 to 70 seconds, with a mean of 20.8 seconds and median of 5 seconds (Table). The drying time for the DERMarker E-Z Removable Ink Mini Skin Marker (Delasco, LLC) with an ST was 5 seconds, while the drying time for the other ST marker, WriteSite Plus Surgical Skin Marker (Aspen Surgical, Inc), was 70 seconds. The FT markers spanned the entire range of drying times. The ink spread width among the markers ranged from 0.53 to 2.27 mm with a median of 0.9 mm and mean of 1.13 mm (Table). The 2 ST markers were found to make some of the widest marks measured, including the WriteSite Plus Surgical Skin Marker, a nonsterile ST marker that created the widest ink marks. The second widest mark was made by an FT marker (Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker [Viscot Medical, LLC]).

To prioritize short drying time coupled with minimal ink spread width, the values associated with each marker were averaged to arrive at the overall score for each marker. The smaller the overall score, the higher we ranked the marker. The Devon Surgical Skin Marker, Dual Tip (Medtronic) ranked the highest among the 13 markers with a final score of 2.78. Runner-up markers included the Sterile Devon Surgical Skin marker, Fine Tip (Medtronic)(final score, 2.86); the Sterile Dual Tip Skin/Utility Marker (Medline Industries, Inc)(final score, 2.86); and the Skin Marker, Fine Tip (Cardinal Health)(final score, 2.89). The 2 lowest-ranking markers were the WriteSite Plus Surgical Skin Marker, an ST marker (final score, 36.13), followed by the Sterile BlephMarker (Viscot Medical, LLC)(final score, 35.27).

Figure 2 shows the drying time and ink spread width for all 13 markers.

Comment

Blepharoplasty surgeons generally agree that meticulous presurgical planning with marking of the eyelids is critical for successful surgical outcomes.^1,2 Fine tip markers have been recommended for this purpose due to the relative precision of the marks, but the prerequisite of these markers is that the marks must have minimal ink spread through skinfolds to allow for precision as well as short drying time to avoid unintentional duplication of the ink on overlapping skin, especially with the likely chance of reflexive blinking by the patient. The associated assumption is that FT markers automatically leave precise marks with minimal drying time. This study systemically compared these 2 qualities for 13 markers, and the results are notable for the unexpected wide range of performance. Although most of the FT markers had ink spread width of less than 1 mm, the Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker was an outlier among FT markers, with ink spread greater than 2 mm, making it too broad and imprecise for practical use. This result indicates that not every FT marker actually makes fine marks. The 2 ST markers in the study—DERMarker E-Z Removable Ink Mini Skin Marker and WriteSite Plus Surgical Skin Marker—left broad marks as anticipated.

The drying time of the markers also ranged from 5 to 70 seconds among both FT and ST markers. Indeed, most of the FT markers were dry at or before 5 seconds of marking, but 2 FT markers—Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker and Sterile BlephMarker—dried at 65 and 70 seconds, respectively. Such a long drying time would be considered impractical for use in blepharoplasty marking and also unexpected of FT markers, which usually are marketed for their precision and efficiency. Notable in the discussion of drying time is that one of the 2 ST markers in the study, the DERMarker E-Z Removable Ink Mini Skin Marker, had the shortest possible drying time of 5 seconds, while the other ST marker, WriteSite Plus Surgical Skin Marker, dried at 70 seconds. This observation coupled with the unexpected results of broad marks and long drying time for some of the FT markers indicates that a surgeon cannot simply assume that a FT marker would provide marks with precision and fast drying time, or that an ST marker would be the opposite.

Future directions for study include the addition of other markers and the extent of resistance to antiseptic routines that can fade the markings.

Conclusion

Among the 13 markers studied, FT markers typically had the shortest drying time and least ink spread on skin. Markers with these qualities rather than those with longer drying times or greater ink spread may be preferred by blepharoplasty surgeons. The dual- and fine-tipped Devon Surgical Skin Markers and the Sterile Dual Tip Skin/Utility Marker had the most favorable scores among the markers included in the study.

Acknowledgement

The authors would like to thank Laura B. Hall, MD (New Haven, Connecticut), for her participation as the volunteer in this study.

Blepharoplasty, or surgical manipulation of the upper and/or lower eyelids, is a commonly performed cosmetic procedure to improve the appearance and function of the eyelids by repositioning and/or removing excess skin and soft tissue from the eyelids, most often through external incisions that minimize scarring and maximize the aesthetic outcomes of the surgery. Therefore, the placement of the incisions is an important determinant of the surgical outcome, and the preoperative marking of the eyelids to indicate where the incisions should be placed is a crucial part of preparation for the surgery.

Preoperative marking has unique challenges due to the dynamicity of the eyelids and the delicate nature of the surgery. The mark must be narrow to minimize the risk of placing the incision higher or lower than intended. The mark also must dry quickly because the patient may blink and create multiple impressions of the marking on skinfolds in contact with the wet ink. Fast drying of the ink used to create the marks improves the efficiency and clarity of the presurgical planning.

We present data on the performance of the various blepharoplasty markers regarding drying time and ink spread width based on an evaluation of 13 surgical markers.

Methods

Eleven unique fine tip (FT) markers and 2 standard tip (ST) markers were obtained based on their accessibility at the researchers’ home institution and availability for direct purchase in small quantities from the distributors (Figure 1). Four markers were double tipped with one FT end and one ST end; for these markers, only the FT end was studied. The experiments were conducted on the bilateral upper eyelids and on hairless patches of skin of a single patient in a minor procedure room with surgical lighting and minimal draft of air. The sole experimenter (J.M.K.) conducting the study was not blinded.

The drying time of each marker was measured by marking 1-in lines on a patch of hairless skin that was first cleaned with an alcohol pad, then dried. Drying time for each marking was measured in increments of 5 seconds; at each time point, the markings were wiped with a single-ply, light-duty tissue under the weight of 10 US quarters to ensure that the same weight/pressure was applied when wiping the skin. Smudges observed with the naked eye on either the wipe or the patients’ skin were interpreted as nondry status of the marking. The first time point at which a marking was found to have no visible smudges either on the skin or the wipe was recorded as the drying time of the respective marker.

Ink spread was measured on clean eyelid skin by drawing curved lines along the natural crease as would be done for actual blepharoplasty planning. Each line was allowed to dry for 2 minutes. The greatest perpendicular spread width along the line observed with the naked eye was measured using a digital Vernier caliper with 0.01-mm graduations. Three measurements were obtained per marker and the values averaged to arrive at the final spread width.

Results

Drying time among the 13 total markers (11 FT and 2 ST) ranged from 5 to 70 seconds, with a mean of 20.8 seconds and median of 5 seconds (Table). The drying time for the DERMarker E-Z Removable Ink Mini Skin Marker (Delasco, LLC) with an ST was 5 seconds, while the drying time for the other ST marker, WriteSite Plus Surgical Skin Marker (Aspen Surgical, Inc), was 70 seconds. The FT markers spanned the entire range of drying times. The ink spread width among the markers ranged from 0.53 to 2.27 mm with a median of 0.9 mm and mean of 1.13 mm (Table). The 2 ST markers were found to make some of the widest marks measured, including the WriteSite Plus Surgical Skin Marker, a nonsterile ST marker that created the widest ink marks. The second widest mark was made by an FT marker (Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker [Viscot Medical, LLC]).

To prioritize short drying time coupled with minimal ink spread width, the values associated with each marker were averaged to arrive at the overall score for each marker. The smaller the overall score, the higher we ranked the marker. The Devon Surgical Skin Marker, Dual Tip (Medtronic) ranked the highest among the 13 markers with a final score of 2.78. Runner-up markers included the Sterile Devon Surgical Skin marker, Fine Tip (Medtronic)(final score, 2.86); the Sterile Dual Tip Skin/Utility Marker (Medline Industries, Inc)(final score, 2.86); and the Skin Marker, Fine Tip (Cardinal Health)(final score, 2.89). The 2 lowest-ranking markers were the WriteSite Plus Surgical Skin Marker, an ST marker (final score, 36.13), followed by the Sterile BlephMarker (Viscot Medical, LLC)(final score, 35.27).

Figure 2 shows the drying time and ink spread width for all 13 markers.

Comment

Blepharoplasty surgeons generally agree that meticulous presurgical planning with marking of the eyelids is critical for successful surgical outcomes.^1,2 Fine tip markers have been recommended for this purpose due to the relative precision of the marks, but the prerequisite of these markers is that the marks must have minimal ink spread through skinfolds to allow for precision as well as short drying time to avoid unintentional duplication of the ink on overlapping skin, especially with the likely chance of reflexive blinking by the patient. The associated assumption is that FT markers automatically leave precise marks with minimal drying time. This study systemically compared these 2 qualities for 13 markers, and the results are notable for the unexpected wide range of performance. Although most of the FT markers had ink spread width of less than 1 mm, the Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker was an outlier among FT markers, with ink spread greater than 2 mm, making it too broad and imprecise for practical use. This result indicates that not every FT marker actually makes fine marks. The 2 ST markers in the study—DERMarker E-Z Removable Ink Mini Skin Marker and WriteSite Plus Surgical Skin Marker—left broad marks as anticipated.

The drying time of the markers also ranged from 5 to 70 seconds among both FT and ST markers. Indeed, most of the FT markers were dry at or before 5 seconds of marking, but 2 FT markers—Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker and Sterile BlephMarker—dried at 65 and 70 seconds, respectively. Such a long drying time would be considered impractical for use in blepharoplasty marking and also unexpected of FT markers, which usually are marketed for their precision and efficiency. Notable in the discussion of drying time is that one of the 2 ST markers in the study, the DERMarker E-Z Removable Ink Mini Skin Marker, had the shortest possible drying time of 5 seconds, while the other ST marker, WriteSite Plus Surgical Skin Marker, dried at 70 seconds. This observation coupled with the unexpected results of broad marks and long drying time for some of the FT markers indicates that a surgeon cannot simply assume that a FT marker would provide marks with precision and fast drying time, or that an ST marker would be the opposite.

Future directions for study include the addition of other markers and the extent of resistance to antiseptic routines that can fade the markings.

Conclusion

Among the 13 markers studied, FT markers typically had the shortest drying time and least ink spread on skin. Markers with these qualities rather than those with longer drying times or greater ink spread may be preferred by blepharoplasty surgeons. The dual- and fine-tipped Devon Surgical Skin Markers and the Sterile Dual Tip Skin/Utility Marker had the most favorable scores among the markers included in the study.

Acknowledgement

The authors would like to thank Laura B. Hall, MD (New Haven, Connecticut), for her participation as the volunteer in this study.

Blepharoplasty, or surgical manipulation of the upper and/or lower eyelids, is a commonly performed cosmetic procedure to improve the appearance and function of the eyelids by repositioning and/or removing excess skin and soft tissue from the eyelids, most often through external incisions that minimize scarring and maximize the aesthetic outcomes of the surgery. Therefore, the placement of the incisions is an important determinant of the surgical outcome, and the preoperative marking of the eyelids to indicate where the incisions should be placed is a crucial part of preparation for the surgery.

Preoperative marking has unique challenges due to the dynamicity of the eyelids and the delicate nature of the surgery. The mark must be narrow to minimize the risk of placing the incision higher or lower than intended. The mark also must dry quickly because the patient may blink and create multiple impressions of the marking on skinfolds in contact with the wet ink. Fast drying of the ink used to create the marks improves the efficiency and clarity of the presurgical planning.

We present data on the performance of the various blepharoplasty markers regarding drying time and ink spread width based on an evaluation of 13 surgical markers.

Methods

Eleven unique fine tip (FT) markers and 2 standard tip (ST) markers were obtained based on their accessibility at the researchers’ home institution and availability for direct purchase in small quantities from the distributors (Figure 1). Four markers were double tipped with one FT end and one ST end; for these markers, only the FT end was studied. The experiments were conducted on the bilateral upper eyelids and on hairless patches of skin of a single patient in a minor procedure room with surgical lighting and minimal draft of air. The sole experimenter (J.M.K.) conducting the study was not blinded.

The drying time of each marker was measured by marking 1-in lines on a patch of hairless skin that was first cleaned with an alcohol pad, then dried. Drying time for each marking was measured in increments of 5 seconds; at each time point, the markings were wiped with a single-ply, light-duty tissue under the weight of 10 US quarters to ensure that the same weight/pressure was applied when wiping the skin. Smudges observed with the naked eye on either the wipe or the patients’ skin were interpreted as nondry status of the marking. The first time point at which a marking was found to have no visible smudges either on the skin or the wipe was recorded as the drying time of the respective marker.

Ink spread was measured on clean eyelid skin by drawing curved lines along the natural crease as would be done for actual blepharoplasty planning. Each line was allowed to dry for 2 minutes. The greatest perpendicular spread width along the line observed with the naked eye was measured using a digital Vernier caliper with 0.01-mm graduations. Three measurements were obtained per marker and the values averaged to arrive at the final spread width.

Results

Drying time among the 13 total markers (11 FT and 2 ST) ranged from 5 to 70 seconds, with a mean of 20.8 seconds and median of 5 seconds (Table). The drying time for the DERMarker E-Z Removable Ink Mini Skin Marker (Delasco, LLC) with an ST was 5 seconds, while the drying time for the other ST marker, WriteSite Plus Surgical Skin Marker (Aspen Surgical, Inc), was 70 seconds. The FT markers spanned the entire range of drying times. The ink spread width among the markers ranged from 0.53 to 2.27 mm with a median of 0.9 mm and mean of 1.13 mm (Table). The 2 ST markers were found to make some of the widest marks measured, including the WriteSite Plus Surgical Skin Marker, a nonsterile ST marker that created the widest ink marks. The second widest mark was made by an FT marker (Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker [Viscot Medical, LLC]).

To prioritize short drying time coupled with minimal ink spread width, the values associated with each marker were averaged to arrive at the overall score for each marker. The smaller the overall score, the higher we ranked the marker. The Devon Surgical Skin Marker, Dual Tip (Medtronic) ranked the highest among the 13 markers with a final score of 2.78. Runner-up markers included the Sterile Devon Surgical Skin marker, Fine Tip (Medtronic)(final score, 2.86); the Sterile Dual Tip Skin/Utility Marker (Medline Industries, Inc)(final score, 2.86); and the Skin Marker, Fine Tip (Cardinal Health)(final score, 2.89). The 2 lowest-ranking markers were the WriteSite Plus Surgical Skin Marker, an ST marker (final score, 36.13), followed by the Sterile BlephMarker (Viscot Medical, LLC)(final score, 35.27).

Figure 2 shows the drying time and ink spread width for all 13 markers.

Comment

Blepharoplasty surgeons generally agree that meticulous presurgical planning with marking of the eyelids is critical for successful surgical outcomes.^1,2 Fine tip markers have been recommended for this purpose due to the relative precision of the marks, but the prerequisite of these markers is that the marks must have minimal ink spread through skinfolds to allow for precision as well as short drying time to avoid unintentional duplication of the ink on overlapping skin, especially with the likely chance of reflexive blinking by the patient. The associated assumption is that FT markers automatically leave precise marks with minimal drying time. This study systemically compared these 2 qualities for 13 markers, and the results are notable for the unexpected wide range of performance. Although most of the FT markers had ink spread width of less than 1 mm, the Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker was an outlier among FT markers, with ink spread greater than 2 mm, making it too broad and imprecise for practical use. This result indicates that not every FT marker actually makes fine marks. The 2 ST markers in the study—DERMarker E-Z Removable Ink Mini Skin Marker and WriteSite Plus Surgical Skin Marker—left broad marks as anticipated.

The drying time of the markers also ranged from 5 to 70 seconds among both FT and ST markers. Indeed, most of the FT markers were dry at or before 5 seconds of marking, but 2 FT markers—Sterile Mini Ultrafine Tip XL Prep Resistant Ink Marker and Sterile BlephMarker—dried at 65 and 70 seconds, respectively. Such a long drying time would be considered impractical for use in blepharoplasty marking and also unexpected of FT markers, which usually are marketed for their precision and efficiency. Notable in the discussion of drying time is that one of the 2 ST markers in the study, the DERMarker E-Z Removable Ink Mini Skin Marker, had the shortest possible drying time of 5 seconds, while the other ST marker, WriteSite Plus Surgical Skin Marker, dried at 70 seconds. This observation coupled with the unexpected results of broad marks and long drying time for some of the FT markers indicates that a surgeon cannot simply assume that a FT marker would provide marks with precision and fast drying time, or that an ST marker would be the opposite.

Future directions for study include the addition of other markers and the extent of resistance to antiseptic routines that can fade the markings.

Conclusion

Among the 13 markers studied, FT markers typically had the shortest drying time and least ink spread on skin. Markers with these qualities rather than those with longer drying times or greater ink spread may be preferred by blepharoplasty surgeons. The dual- and fine-tipped Devon Surgical Skin Markers and the Sterile Dual Tip Skin/Utility Marker had the most favorable scores among the markers included in the study.

Acknowledgement

The authors would like to thank Laura B. Hall, MD (New Haven, Connecticut), for her participation as the volunteer in this study.

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

The White House pick for the newly created post of mental health czar has raised some hackles on Capitol Hill.

President Donald Trump recently announced that Elinore “Ellie” F. McCance-Katz, MD, PhD, a psychiatrist whose career has focused on substance abuse and addiction, was his nominee to serve as nation’s first assistant secretary for mental health and substance use. In 2013, Dr. McCance-Katz served as the Substance Abuse and Mental Health Services Administration’s first chief medical officer. She resigned after 2 years.

The choice does not sit well with Rep. Tim Murphy (R-Pa.), whose landmark legislation, Helping Families in Mental Health Crisis – ultimately passed as part of the bipartisan 21st Century Cures Act – created the cabinet-level post to help end what many have seen as SAMHSA’s poor performance in meeting the nation’s mental health needs.

“I am stunned the president put forth a nominee who served in a key post at SAMHSA under the previous administration when the agency was actively opposing the transformative changes in H.R. 3717, the original version of my Helping Families in Mental Health Crisis Act,” Rep. Murphy said in a statement. “After an intensive investigation bringing to light the many leadership failures across the federal government, but particularly at SAMHSA, I drafted strong legislation to fix the broken mental health system. One of the most critical reforms was restructuring the agency, focusing on evidence-based models of care and establishing an assistant secretary within [the Department of Health & Human Services] to put an end to what the Government Accountability Office termed a lack of leadership.”

Key provisions of the legislation include clearer HIPAA language, expanded access to inpatient psychiatric hospital beds, and a stronger and more streamlined federal commitment to evidence-based practices in mental and behavioral health care delivery.

The American Psychiatric Association, however, endorsed the nomination and called for swift confirmation by the Senate. “We look forward to working with her to improve the quality of care of mental health and substance use disorders,” APA CEO and Medical Director Saul Levin, MD, said in a statement.

Currently, Dr. McCance-Katz is the chief medical officer for Rhode Island’s department of behavioral health care, developmental disabilities, and hospitals. Dr. McCance-Katz, widely regarded as an expert in medication-assisted treatment for substance use disorders, among other addiction-related specialties, also is a former California department of alcohol and drug programs state medical director.

Since leaving her previous post at SAMHSA, Dr. McCance-Katz has been an outspoken critic of the agency she is now being tapped to run. She once editorialized against what she called its poor performance in addressing the needs of people with serious mental illness and its “hostility toward psychiatric medicine.”

Rep. Murphy’s own reported preference for the role was Michael Welner, MD, a forensic psychiatrist upon whom the congressman – himself a clinical psychologist – relied on in part to help craft his mental health legislation. According to mental health blogger Pete Early – who often writes about his son’s struggles with bipolar disorder – the announcement is a surprise to many who expected Dr. Welner to be the pick. On his blog, Mr. Early wrote that Senate sources had told him that Dr. Welner, who publicly supports President Trump, “had a lock on the job.”

Several other names were floated for the position, according to Mr. Early, including John Wernert, MD, who served as head of Indiana’s mental health policy under then-governor, Vice President Mike Pence, and Miami-Dade County, Fla., Judge Steve Leifman, known for his interest in diverting those with serious mental illness from the criminal justice system and into treatment. However, the judge did not have an advanced medical degree, as stipulated by the law, a provision pushed by Rep. Murphy to safeguard against what he said was SAMHSA’s antipsychiatry stance.

In an APA blog post, APA President Maria A. Oquendo, MD, PhD, said Dr. McCance-Katz would “bring a wealth of knowledge in the prevention, treatment, and recovery of substance use disorders” that challenge the United States. “APA strongly supports her appointment.”

Dr. McCance-Katz’s nomination will go before the Senate’s Committee on Health, Education, Labor, and Pensions, which is chaired by Sen. Lamar Alexander (R-Tenn.). His office said the senator “looks forward to learning more about how Dr. McCance-Katz would use her experience in medicine and government to implement the new mental health law passed last Congress to help the one in five adults in this country suffering from a mental illness receive the treatment they need.”

[email protected]

On Twitter @whitneymcknight

The White House pick for the newly created post of mental health czar has raised some hackles on Capitol Hill.

President Donald Trump recently announced that Elinore “Ellie” F. McCance-Katz, MD, PhD, a psychiatrist whose career has focused on substance abuse and addiction, was his nominee to serve as nation’s first assistant secretary for mental health and substance use. In 2013, Dr. McCance-Katz served as the Substance Abuse and Mental Health Services Administration’s first chief medical officer. She resigned after 2 years.

The choice does not sit well with Rep. Tim Murphy (R-Pa.), whose landmark legislation, Helping Families in Mental Health Crisis – ultimately passed as part of the bipartisan 21st Century Cures Act – created the cabinet-level post to help end what many have seen as SAMHSA’s poor performance in meeting the nation’s mental health needs.

“I am stunned the president put forth a nominee who served in a key post at SAMHSA under the previous administration when the agency was actively opposing the transformative changes in H.R. 3717, the original version of my Helping Families in Mental Health Crisis Act,” Rep. Murphy said in a statement. “After an intensive investigation bringing to light the many leadership failures across the federal government, but particularly at SAMHSA, I drafted strong legislation to fix the broken mental health system. One of the most critical reforms was restructuring the agency, focusing on evidence-based models of care and establishing an assistant secretary within [the Department of Health & Human Services] to put an end to what the Government Accountability Office termed a lack of leadership.”

Key provisions of the legislation include clearer HIPAA language, expanded access to inpatient psychiatric hospital beds, and a stronger and more streamlined federal commitment to evidence-based practices in mental and behavioral health care delivery.

The American Psychiatric Association, however, endorsed the nomination and called for swift confirmation by the Senate. “We look forward to working with her to improve the quality of care of mental health and substance use disorders,” APA CEO and Medical Director Saul Levin, MD, said in a statement.

Currently, Dr. McCance-Katz is the chief medical officer for Rhode Island’s department of behavioral health care, developmental disabilities, and hospitals. Dr. McCance-Katz, widely regarded as an expert in medication-assisted treatment for substance use disorders, among other addiction-related specialties, also is a former California department of alcohol and drug programs state medical director.

Since leaving her previous post at SAMHSA, Dr. McCance-Katz has been an outspoken critic of the agency she is now being tapped to run. She once editorialized against what she called its poor performance in addressing the needs of people with serious mental illness and its “hostility toward psychiatric medicine.”

Rep. Murphy’s own reported preference for the role was Michael Welner, MD, a forensic psychiatrist upon whom the congressman – himself a clinical psychologist – relied on in part to help craft his mental health legislation. According to mental health blogger Pete Early – who often writes about his son’s struggles with bipolar disorder – the announcement is a surprise to many who expected Dr. Welner to be the pick. On his blog, Mr. Early wrote that Senate sources had told him that Dr. Welner, who publicly supports President Trump, “had a lock on the job.”

Several other names were floated for the position, according to Mr. Early, including John Wernert, MD, who served as head of Indiana’s mental health policy under then-governor, Vice President Mike Pence, and Miami-Dade County, Fla., Judge Steve Leifman, known for his interest in diverting those with serious mental illness from the criminal justice system and into treatment. However, the judge did not have an advanced medical degree, as stipulated by the law, a provision pushed by Rep. Murphy to safeguard against what he said was SAMHSA’s antipsychiatry stance.

In an APA blog post, APA President Maria A. Oquendo, MD, PhD, said Dr. McCance-Katz would “bring a wealth of knowledge in the prevention, treatment, and recovery of substance use disorders” that challenge the United States. “APA strongly supports her appointment.”

Dr. McCance-Katz’s nomination will go before the Senate’s Committee on Health, Education, Labor, and Pensions, which is chaired by Sen. Lamar Alexander (R-Tenn.). His office said the senator “looks forward to learning more about how Dr. McCance-Katz would use her experience in medicine and government to implement the new mental health law passed last Congress to help the one in five adults in this country suffering from a mental illness receive the treatment they need.”

[email protected]

On Twitter @whitneymcknight

The White House pick for the newly created post of mental health czar has raised some hackles on Capitol Hill.

President Donald Trump recently announced that Elinore “Ellie” F. McCance-Katz, MD, PhD, a psychiatrist whose career has focused on substance abuse and addiction, was his nominee to serve as nation’s first assistant secretary for mental health and substance use. In 2013, Dr. McCance-Katz served as the Substance Abuse and Mental Health Services Administration’s first chief medical officer. She resigned after 2 years.

The choice does not sit well with Rep. Tim Murphy (R-Pa.), whose landmark legislation, Helping Families in Mental Health Crisis – ultimately passed as part of the bipartisan 21st Century Cures Act – created the cabinet-level post to help end what many have seen as SAMHSA’s poor performance in meeting the nation’s mental health needs.

“I am stunned the president put forth a nominee who served in a key post at SAMHSA under the previous administration when the agency was actively opposing the transformative changes in H.R. 3717, the original version of my Helping Families in Mental Health Crisis Act,” Rep. Murphy said in a statement. “After an intensive investigation bringing to light the many leadership failures across the federal government, but particularly at SAMHSA, I drafted strong legislation to fix the broken mental health system. One of the most critical reforms was restructuring the agency, focusing on evidence-based models of care and establishing an assistant secretary within [the Department of Health & Human Services] to put an end to what the Government Accountability Office termed a lack of leadership.”

Key provisions of the legislation include clearer HIPAA language, expanded access to inpatient psychiatric hospital beds, and a stronger and more streamlined federal commitment to evidence-based practices in mental and behavioral health care delivery.

The American Psychiatric Association, however, endorsed the nomination and called for swift confirmation by the Senate. “We look forward to working with her to improve the quality of care of mental health and substance use disorders,” APA CEO and Medical Director Saul Levin, MD, said in a statement.

Currently, Dr. McCance-Katz is the chief medical officer for Rhode Island’s department of behavioral health care, developmental disabilities, and hospitals. Dr. McCance-Katz, widely regarded as an expert in medication-assisted treatment for substance use disorders, among other addiction-related specialties, also is a former California department of alcohol and drug programs state medical director.

Since leaving her previous post at SAMHSA, Dr. McCance-Katz has been an outspoken critic of the agency she is now being tapped to run. She once editorialized against what she called its poor performance in addressing the needs of people with serious mental illness and its “hostility toward psychiatric medicine.”

Rep. Murphy’s own reported preference for the role was Michael Welner, MD, a forensic psychiatrist upon whom the congressman – himself a clinical psychologist – relied on in part to help craft his mental health legislation. According to mental health blogger Pete Early – who often writes about his son’s struggles with bipolar disorder – the announcement is a surprise to many who expected Dr. Welner to be the pick. On his blog, Mr. Early wrote that Senate sources had told him that Dr. Welner, who publicly supports President Trump, “had a lock on the job.”

Several other names were floated for the position, according to Mr. Early, including John Wernert, MD, who served as head of Indiana’s mental health policy under then-governor, Vice President Mike Pence, and Miami-Dade County, Fla., Judge Steve Leifman, known for his interest in diverting those with serious mental illness from the criminal justice system and into treatment. However, the judge did not have an advanced medical degree, as stipulated by the law, a provision pushed by Rep. Murphy to safeguard against what he said was SAMHSA’s antipsychiatry stance.

In an APA blog post, APA President Maria A. Oquendo, MD, PhD, said Dr. McCance-Katz would “bring a wealth of knowledge in the prevention, treatment, and recovery of substance use disorders” that challenge the United States. “APA strongly supports her appointment.”

Dr. McCance-Katz’s nomination will go before the Senate’s Committee on Health, Education, Labor, and Pensions, which is chaired by Sen. Lamar Alexander (R-Tenn.). His office said the senator “looks forward to learning more about how Dr. McCance-Katz would use her experience in medicine and government to implement the new mental health law passed last Congress to help the one in five adults in this country suffering from a mental illness receive the treatment they need.”

[email protected]

On Twitter @whitneymcknight

Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Jennifer Myers, director of quality and safety education at the University of Pennsylvania, Philadelphia.

Even as a junior physician, Jennifer Myers, MD, FHM, embraced the complexities of the hospital system and the opportunity to transform patient care. She was one of the first hospitalists to participate in and lead quality improvement (QI) work at the University of Pennsylvania Medical Center more than 10 years ago, where, “in that role, I got to know almost everyone in the hospital and got an up-close view of how the hospital works administratively,” she recalled.

The experience taught Dr. Myers how little she knew at that time about hospital operations, and she convinced hospital administrators that a mechanism was needed to prepare the next generation of leaders in QI and patient safety. In 2011, with the support of a career development award from the Josiah Macy Jr. Foundation, Dr. Myers formulated a quality and patient safety curriculum for residents of Penn Medicine, as well as a more basic introductory program for medical students.

Claudia Stahl is a content manager for the Society of Hospital Medicine.

Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Jennifer Myers, director of quality and safety education at the University of Pennsylvania, Philadelphia.

Even as a junior physician, Jennifer Myers, MD, FHM, embraced the complexities of the hospital system and the opportunity to transform patient care. She was one of the first hospitalists to participate in and lead quality improvement (QI) work at the University of Pennsylvania Medical Center more than 10 years ago, where, “in that role, I got to know almost everyone in the hospital and got an up-close view of how the hospital works administratively,” she recalled.

The experience taught Dr. Myers how little she knew at that time about hospital operations, and she convinced hospital administrators that a mechanism was needed to prepare the next generation of leaders in QI and patient safety. In 2011, with the support of a career development award from the Josiah Macy Jr. Foundation, Dr. Myers formulated a quality and patient safety curriculum for residents of Penn Medicine, as well as a more basic introductory program for medical students.

Claudia Stahl is a content manager for the Society of Hospital Medicine.

Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Jennifer Myers, director of quality and safety education at the University of Pennsylvania, Philadelphia.

Even as a junior physician, Jennifer Myers, MD, FHM, embraced the complexities of the hospital system and the opportunity to transform patient care. She was one of the first hospitalists to participate in and lead quality improvement (QI) work at the University of Pennsylvania Medical Center more than 10 years ago, where, “in that role, I got to know almost everyone in the hospital and got an up-close view of how the hospital works administratively,” she recalled.

The experience taught Dr. Myers how little she knew at that time about hospital operations, and she convinced hospital administrators that a mechanism was needed to prepare the next generation of leaders in QI and patient safety. In 2011, with the support of a career development award from the Josiah Macy Jr. Foundation, Dr. Myers formulated a quality and patient safety curriculum for residents of Penn Medicine, as well as a more basic introductory program for medical students.

Claudia Stahl is a content manager for the Society of Hospital Medicine.

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

[email protected]

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

[email protected]

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

[email protected]