Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

A version of this article first appeared on Medscape.com.

Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

A version of this article first appeared on Medscape.com.

Two of the three late-breaking abstract sessions coming up this week at IDWeek 2021, an annual scientific meeting on infectious diseases, are filled with the most recent evidence on COVID-19 prevention and treatment.

Adarsh Bhimraj, MD, a vice chair of the conference, said in an interview that attendees will leave the virtual conference with an up-to-date view of what’s promising in the fight against COVID-19 globally and what questions are as yet unanswered.

Researchers will also present findings on promising new antibiotics in the pipeline, stewardship efforts, health disparities, telemedicine advances, and emerging pathogens, but at least a quarter of the program is devoted to COVID-19.

“It’s hard to ignore the elephant in the room,” Dr. Bhimraj said.

Vaccine distribution will be among the hot topics at the global conference, he said, in light of the recent decisions by the Food and Drug Administration and the Centers for Disease Control and Prevention to reserve boosters for those at greatest risk.

Although the United States and other high-resource countries are deciding who should get boosters, only 10% of the developing world has received even a single dose, he noted.

The conference will also present a worldwide view of scientific collaboration to address the COVID pandemic and pandemics yet to come, Dr. Bhimraj said.

He highlighted a talk on Oct. 2, to be delivered by South African human rights attorney and social justice activist Fatima Hassan, called “Global Vaccines and Preventive Care Inequities: Implications and Solutions Beyond the Pandemic.”

The session looks ahead to building systems to share resources and knowledge to end deadly outbreaks with an equitable approach.

“We live in a global village,” Dr. Bhimraj said. “It isn’t just the right thing to do, it’s the pragmatic thing to do.”
 

Controversies in non-COVID diseases

Controversies and new treatments are plentiful in other diseases as well.

• At an HIV session, arguments will be presented regarding the sustainability and practicalities of telemedicine in HIV. Speakers will argue for and against telemedicine as a permanent practice changer for the field.
• In a session on Oct. 1, panelists will discuss pros and cons of information published in preprints versus peer-reviewed journals and how to assess when research findings should lead to practice change.
• Also on Oct. 1, panelists in a symposium will discuss advantages and disadvantages of antifungal treatments for children who have received solid organ transplants.
• Antimicrobial stewardship continues to be a primary topic at IDWeek, this year with additional pandemic challenges. Sessions will address trends in use and diagnostic advances to help in prescribing.
• The pipeline for new antibiotics continues to face barriers regarding production and development. No new classes of antibiotics have been discovered since the 1980s. Pew has that there are too few drugs in development to meet current and anticipated need.
• This year’s program offers a symposium on private-public partnerships to help jump-start development.
• One of the most popular sessions returning this year is “Clinical Trials That Will Change Your Practice,” Dr. Bhimraj said. This year, that session will be reserved for non-COVID infectious disease research. Presenters will summarize the findings of top work published in the past year.

Around-the-world COVID view

Again this year, global experts will present a round-the-clock session called “Chasing the Sun” the day before the main sessions. It will include updates on COVID throughout the world. Barney Graham, MD, PhD, deputy director of the National Institutes of Health’s Vaccine Research Center, will kick off the program with an address on the future of vaccinology. This will be followed by updates on the state of the disease in Central and South America, Japan, Asia Pacific, India, and Africa.

Sandra Harwood, IDWeek conference secretariat, who proposed the idea for the first Chasing the Sun session last year, said in an interview that the updates will highlight particular COVID challenges experienced in various countries.

For example, leaders of India’s session will address why a potentially fatal fungal disease struck many COVID-19 patients in that country. Japan’s update will include how Olympic organizers planned for and dealt with the virus’s threat in Tokyo.

Ms. Harwood said that all the COVID sessions in Chasing the Sun and throughout the program will be free to clinicians inside and outside the conference, thanks to a grant from the CDC.

An address by CDC Director Rochelle Walensky, MD, MPH, on Sept. 30 will wrap up Chasing the Sun and launch the main IDWeek program.

A version of this article first appeared on Medscape.com.

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

A combination of magnetic resonance elastography and blood levels of fibrosis-4 index (MEFIB) outperformed FibroScan-AST (FAST) in determining the presence of significant fibrosis among patients with nonalcoholic fatty liver disease (NAFLD), according to a new prospective cohort analysis.

© parisvas/Thinkstock

Liver fibrosis is the most important prognostic factor for NAFLD, but the invasiveness, propensity for sampling error, and interoperator variability of biopsy have prompted efforts to develop alternatives. FAST, which uses vibration-controlled transient elastography (VCTE), controlled attenuation parameter (CAP), and aspartate aminotransferase levels, and MEFIB have been developed as candidates, but they had not been directly compared in screening. The findings suggest that MEFIB may be a better tool for identifying NAFLD patients at heightened risk of nonalcoholic steatohepatitis (NASH), as well as which patients could be candidates for pharmacotherapy interventions and clinical trials.

Although there are no drugs currently approved for high-risk NAFLD patients, many clinical trials are underway. Patients with stage 2 or higher fibrosis are candidates for clinical trials, but many trials experience a high screening failure rate. A noninvasive method that can identify clinical trial candidates while avoiding liver biopsy would be a welcome addition, Nobuharu Tamaki, MD, PhD, of the NAFLD Research Center, division of gastroenterology and hepatology, department of medicine, at the University of California, San Diego, and colleagues explained in Hepatology.

“We suspect that these are the patients; if there is going to be a drug approved, it will be for this patient population. So it’s important for prognosis, but it’s also important potentially for future treatment with new drugs,” said Zobair Younossi, MD, who was asked to comment on the study.

The researchers examined a cohort of 234 consecutive adults at UCSD and 314 consecutive adults at Yokohama (Japan) City University who underwent liver biopsy, magnetic resonance elastography (MRE), VCTE, and CAP assessment.

Significant fibrosis was found in 29.5% of the UCSD cohort and 66.2% of the Yokohama cohort.* MEFIB had a higher area under the receiver operating characteristic curve than FAST in the UCSD cohort (0.860 vs. 0.757; P = .005) and the Yokohama cohort (0.899 vs. 0.724; P < .001).

When the researchers employed MEFIB as a rule-in criteria (MRE value ≥3.3 kPa and FIB-4 ≥1.6), MEFIB had a positive predictive value of 91.2% in the UCSD cohort and 96.0% in the Yokohama cohort, versus 74.2% and 89.2% for FAST (≥0.67), respectively. Rule-out criteria included MRE less than 3.3 kPa and Fib-4 less than1.6 for MEFIB, as well as FAST of 0.35 or less; with those parameters, negative predictive value for significant fibrosis was 92.8% in the UCSD group and 85.6% in the Yokohama group for MEFIB, and 88.3% and 57.8% for FAST, respectively.

Most existing noninvasive tests do a pretty good job of excluding advanced fibrosis, but they don’t perform as well at identifying those with cirrhosis, according to Dr. Younossi. He added that MEFIB isn’t suitable for general population screening, but rather for case finding, in which it can be used to identify patients who are likely to have high risk for fibrosis. “Nevertheless, it seems like the combination of FIB-4 and MRE has very good performance for identifying and excluding NAFLD patients with moderate to advance fibrosis, at least in the two cohorts that were looked at,” said Dr. Younossi.

However, Dr. Younossi noted some potential limitations to the study. Both cohorts were from referral centers, making it likely that the included patients have higher prevalences of fibrosis than a typical practice patient population, making it important to validate the findings in a real-world setting. The approach also relies on magnetic resonance technology, which is costly and may not be readily available. “We need to potentially find other, simpler noninvasive test combinations that are easier to do than MRE,” said Dr. Younossi.

Several authors disclosed ties with numerous pharmaceutical and device companies, including Pfizer, AstraZeneca, and Siemens. Dr. Younossi has no relevant financial disclosures.

Correction, 1/18/22: An earlier version of this article misstated the percentage of each cohort that had significant fibrosis.

A combination of magnetic resonance elastography and blood levels of fibrosis-4 index (MEFIB) outperformed FibroScan-AST (FAST) in determining the presence of significant fibrosis among patients with nonalcoholic fatty liver disease (NAFLD), according to a new prospective cohort analysis.

© parisvas/Thinkstock

Liver fibrosis is the most important prognostic factor for NAFLD, but the invasiveness, propensity for sampling error, and interoperator variability of biopsy have prompted efforts to develop alternatives. FAST, which uses vibration-controlled transient elastography (VCTE), controlled attenuation parameter (CAP), and aspartate aminotransferase levels, and MEFIB have been developed as candidates, but they had not been directly compared in screening. The findings suggest that MEFIB may be a better tool for identifying NAFLD patients at heightened risk of nonalcoholic steatohepatitis (NASH), as well as which patients could be candidates for pharmacotherapy interventions and clinical trials.

Although there are no drugs currently approved for high-risk NAFLD patients, many clinical trials are underway. Patients with stage 2 or higher fibrosis are candidates for clinical trials, but many trials experience a high screening failure rate. A noninvasive method that can identify clinical trial candidates while avoiding liver biopsy would be a welcome addition, Nobuharu Tamaki, MD, PhD, of the NAFLD Research Center, division of gastroenterology and hepatology, department of medicine, at the University of California, San Diego, and colleagues explained in Hepatology.

“We suspect that these are the patients; if there is going to be a drug approved, it will be for this patient population. So it’s important for prognosis, but it’s also important potentially for future treatment with new drugs,” said Zobair Younossi, MD, who was asked to comment on the study.

The researchers examined a cohort of 234 consecutive adults at UCSD and 314 consecutive adults at Yokohama (Japan) City University who underwent liver biopsy, magnetic resonance elastography (MRE), VCTE, and CAP assessment.

Significant fibrosis was found in 29.5% of the UCSD cohort and 66.2% of the Yokohama cohort.* MEFIB had a higher area under the receiver operating characteristic curve than FAST in the UCSD cohort (0.860 vs. 0.757; P = .005) and the Yokohama cohort (0.899 vs. 0.724; P < .001).

When the researchers employed MEFIB as a rule-in criteria (MRE value ≥3.3 kPa and FIB-4 ≥1.6), MEFIB had a positive predictive value of 91.2% in the UCSD cohort and 96.0% in the Yokohama cohort, versus 74.2% and 89.2% for FAST (≥0.67), respectively. Rule-out criteria included MRE less than 3.3 kPa and Fib-4 less than1.6 for MEFIB, as well as FAST of 0.35 or less; with those parameters, negative predictive value for significant fibrosis was 92.8% in the UCSD group and 85.6% in the Yokohama group for MEFIB, and 88.3% and 57.8% for FAST, respectively.

Most existing noninvasive tests do a pretty good job of excluding advanced fibrosis, but they don’t perform as well at identifying those with cirrhosis, according to Dr. Younossi. He added that MEFIB isn’t suitable for general population screening, but rather for case finding, in which it can be used to identify patients who are likely to have high risk for fibrosis. “Nevertheless, it seems like the combination of FIB-4 and MRE has very good performance for identifying and excluding NAFLD patients with moderate to advance fibrosis, at least in the two cohorts that were looked at,” said Dr. Younossi.

However, Dr. Younossi noted some potential limitations to the study. Both cohorts were from referral centers, making it likely that the included patients have higher prevalences of fibrosis than a typical practice patient population, making it important to validate the findings in a real-world setting. The approach also relies on magnetic resonance technology, which is costly and may not be readily available. “We need to potentially find other, simpler noninvasive test combinations that are easier to do than MRE,” said Dr. Younossi.

Several authors disclosed ties with numerous pharmaceutical and device companies, including Pfizer, AstraZeneca, and Siemens. Dr. Younossi has no relevant financial disclosures.

Correction, 1/18/22: An earlier version of this article misstated the percentage of each cohort that had significant fibrosis.

A combination of magnetic resonance elastography and blood levels of fibrosis-4 index (MEFIB) outperformed FibroScan-AST (FAST) in determining the presence of significant fibrosis among patients with nonalcoholic fatty liver disease (NAFLD), according to a new prospective cohort analysis.

© parisvas/Thinkstock

Liver fibrosis is the most important prognostic factor for NAFLD, but the invasiveness, propensity for sampling error, and interoperator variability of biopsy have prompted efforts to develop alternatives. FAST, which uses vibration-controlled transient elastography (VCTE), controlled attenuation parameter (CAP), and aspartate aminotransferase levels, and MEFIB have been developed as candidates, but they had not been directly compared in screening. The findings suggest that MEFIB may be a better tool for identifying NAFLD patients at heightened risk of nonalcoholic steatohepatitis (NASH), as well as which patients could be candidates for pharmacotherapy interventions and clinical trials.

Although there are no drugs currently approved for high-risk NAFLD patients, many clinical trials are underway. Patients with stage 2 or higher fibrosis are candidates for clinical trials, but many trials experience a high screening failure rate. A noninvasive method that can identify clinical trial candidates while avoiding liver biopsy would be a welcome addition, Nobuharu Tamaki, MD, PhD, of the NAFLD Research Center, division of gastroenterology and hepatology, department of medicine, at the University of California, San Diego, and colleagues explained in Hepatology.

“We suspect that these are the patients; if there is going to be a drug approved, it will be for this patient population. So it’s important for prognosis, but it’s also important potentially for future treatment with new drugs,” said Zobair Younossi, MD, who was asked to comment on the study.

The researchers examined a cohort of 234 consecutive adults at UCSD and 314 consecutive adults at Yokohama (Japan) City University who underwent liver biopsy, magnetic resonance elastography (MRE), VCTE, and CAP assessment.

Significant fibrosis was found in 29.5% of the UCSD cohort and 66.2% of the Yokohama cohort.* MEFIB had a higher area under the receiver operating characteristic curve than FAST in the UCSD cohort (0.860 vs. 0.757; P = .005) and the Yokohama cohort (0.899 vs. 0.724; P < .001).

When the researchers employed MEFIB as a rule-in criteria (MRE value ≥3.3 kPa and FIB-4 ≥1.6), MEFIB had a positive predictive value of 91.2% in the UCSD cohort and 96.0% in the Yokohama cohort, versus 74.2% and 89.2% for FAST (≥0.67), respectively. Rule-out criteria included MRE less than 3.3 kPa and Fib-4 less than1.6 for MEFIB, as well as FAST of 0.35 or less; with those parameters, negative predictive value for significant fibrosis was 92.8% in the UCSD group and 85.6% in the Yokohama group for MEFIB, and 88.3% and 57.8% for FAST, respectively.

Most existing noninvasive tests do a pretty good job of excluding advanced fibrosis, but they don’t perform as well at identifying those with cirrhosis, according to Dr. Younossi. He added that MEFIB isn’t suitable for general population screening, but rather for case finding, in which it can be used to identify patients who are likely to have high risk for fibrosis. “Nevertheless, it seems like the combination of FIB-4 and MRE has very good performance for identifying and excluding NAFLD patients with moderate to advance fibrosis, at least in the two cohorts that were looked at,” said Dr. Younossi.

However, Dr. Younossi noted some potential limitations to the study. Both cohorts were from referral centers, making it likely that the included patients have higher prevalences of fibrosis than a typical practice patient population, making it important to validate the findings in a real-world setting. The approach also relies on magnetic resonance technology, which is costly and may not be readily available. “We need to potentially find other, simpler noninvasive test combinations that are easier to do than MRE,” said Dr. Younossi.

Several authors disclosed ties with numerous pharmaceutical and device companies, including Pfizer, AstraZeneca, and Siemens. Dr. Younossi has no relevant financial disclosures.

Correction, 1/18/22: An earlier version of this article misstated the percentage of each cohort that had significant fibrosis.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.