Federal Practitioner

Two recently published studies indicate that COVID-19 infections were already circulating in the United States in December 2019. The question is whether these methodologies that could be applied to track the next pandemic.

One study evaluating blood donations found antibodies on the West coast as early as Dec. 13, 2019, and in blood donated on the East Coast by early January 2020 (Clin Infect Dis. 2020; Nov 30. doi: 10.1093/cid/ciaa1785). Both preceded the first documented COVID-19 infection in the United States, which has been widely reported as occurring on Jan. 19, 2020, in a traveler returning from China.

The other study, utilizing electronic medical record (EMR) analytics, demonstrated a spike in visits or hospitalizations for cough, a trend that persisted from Dec. 22, 2019, onward, exceeding norms for seasonal flu ( J Med Internet Res. 2020;22:e21562). This spike was interpreted as evidence that the SARS-CoV-2 pandemic was already underway before the first case was established.

While the ongoing serologic testing of blood donations for viral antibodies “will advance understanding of the epidemiology” for SARS-CoV-2 and “inform allocation of resources and public health prevention interventions to mitigate morbidity and mortality,” it might also be a strategy for disease surveillance in the next pandemic, according to a team led by investigators at the Centers for Disease Control and Prevention.

Blood donation surveillance is not now used routinely to monitor for population-based health threats, but it is not a new idea, according to the lead author of the study, Sridhar V. Basavaraju, MD, of Emory University and director of the CDC’s Office of Blood, Organ, and Other Tissue Safety, Atlanta, and his coinvestigators. Most recently, blood donation surveillance was used in the United States to track the penetration of the Zika virus.

For early detection of respiratory infections, blood donations might have unique advantages over alternatives, such as surveillance of respiratory specimens from symptomatic patients. Not least, blood donation surveillance captures individuals who are not seeking medical care, according to the investigators.

EMR surveillance might also have unique advantages for population-based monitoring of health threats. For one, aggregate data from large EMR systems have the potential to reveal symptom patterns before they become apparent at level of clinical care, according to a team of collaborating investigators from the University of California, Los Angeles, and the University of Washington, Seattle.

Emphasizing an urgent need for “agile healthcare analytics” to enable “disease surveillance in real time,” the first author of the EMR study, Joann G. Elmore, MD, professor in the department of health policy and management at the University of California, Los Angeles, expressed the hope that the approach will “lead to better preparation and the ability to quickly provide warnings and track the next pandemic.”

SOURCE: Basavaraju SV et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1785); Elmore JG et al. J Med Internet Res. 2020;22:e21562).

Two recently published studies indicate that COVID-19 infections were already circulating in the United States in December 2019. The question is whether these methodologies that could be applied to track the next pandemic.

One study evaluating blood donations found antibodies on the West coast as early as Dec. 13, 2019, and in blood donated on the East Coast by early January 2020 (Clin Infect Dis. 2020; Nov 30. doi: 10.1093/cid/ciaa1785). Both preceded the first documented COVID-19 infection in the United States, which has been widely reported as occurring on Jan. 19, 2020, in a traveler returning from China.

The other study, utilizing electronic medical record (EMR) analytics, demonstrated a spike in visits or hospitalizations for cough, a trend that persisted from Dec. 22, 2019, onward, exceeding norms for seasonal flu ( J Med Internet Res. 2020;22:e21562). This spike was interpreted as evidence that the SARS-CoV-2 pandemic was already underway before the first case was established.

While the ongoing serologic testing of blood donations for viral antibodies “will advance understanding of the epidemiology” for SARS-CoV-2 and “inform allocation of resources and public health prevention interventions to mitigate morbidity and mortality,” it might also be a strategy for disease surveillance in the next pandemic, according to a team led by investigators at the Centers for Disease Control and Prevention.

Blood donation surveillance is not now used routinely to monitor for population-based health threats, but it is not a new idea, according to the lead author of the study, Sridhar V. Basavaraju, MD, of Emory University and director of the CDC’s Office of Blood, Organ, and Other Tissue Safety, Atlanta, and his coinvestigators. Most recently, blood donation surveillance was used in the United States to track the penetration of the Zika virus.

For early detection of respiratory infections, blood donations might have unique advantages over alternatives, such as surveillance of respiratory specimens from symptomatic patients. Not least, blood donation surveillance captures individuals who are not seeking medical care, according to the investigators.

EMR surveillance might also have unique advantages for population-based monitoring of health threats. For one, aggregate data from large EMR systems have the potential to reveal symptom patterns before they become apparent at level of clinical care, according to a team of collaborating investigators from the University of California, Los Angeles, and the University of Washington, Seattle.

Emphasizing an urgent need for “agile healthcare analytics” to enable “disease surveillance in real time,” the first author of the EMR study, Joann G. Elmore, MD, professor in the department of health policy and management at the University of California, Los Angeles, expressed the hope that the approach will “lead to better preparation and the ability to quickly provide warnings and track the next pandemic.”

SOURCE: Basavaraju SV et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1785); Elmore JG et al. J Med Internet Res. 2020;22:e21562).

Two recently published studies indicate that COVID-19 infections were already circulating in the United States in December 2019. The question is whether these methodologies that could be applied to track the next pandemic.

One study evaluating blood donations found antibodies on the West coast as early as Dec. 13, 2019, and in blood donated on the East Coast by early January 2020 (Clin Infect Dis. 2020; Nov 30. doi: 10.1093/cid/ciaa1785). Both preceded the first documented COVID-19 infection in the United States, which has been widely reported as occurring on Jan. 19, 2020, in a traveler returning from China.

The other study, utilizing electronic medical record (EMR) analytics, demonstrated a spike in visits or hospitalizations for cough, a trend that persisted from Dec. 22, 2019, onward, exceeding norms for seasonal flu ( J Med Internet Res. 2020;22:e21562). This spike was interpreted as evidence that the SARS-CoV-2 pandemic was already underway before the first case was established.

While the ongoing serologic testing of blood donations for viral antibodies “will advance understanding of the epidemiology” for SARS-CoV-2 and “inform allocation of resources and public health prevention interventions to mitigate morbidity and mortality,” it might also be a strategy for disease surveillance in the next pandemic, according to a team led by investigators at the Centers for Disease Control and Prevention.

Blood donation surveillance is not now used routinely to monitor for population-based health threats, but it is not a new idea, according to the lead author of the study, Sridhar V. Basavaraju, MD, of Emory University and director of the CDC’s Office of Blood, Organ, and Other Tissue Safety, Atlanta, and his coinvestigators. Most recently, blood donation surveillance was used in the United States to track the penetration of the Zika virus.

For early detection of respiratory infections, blood donations might have unique advantages over alternatives, such as surveillance of respiratory specimens from symptomatic patients. Not least, blood donation surveillance captures individuals who are not seeking medical care, according to the investigators.

EMR surveillance might also have unique advantages for population-based monitoring of health threats. For one, aggregate data from large EMR systems have the potential to reveal symptom patterns before they become apparent at level of clinical care, according to a team of collaborating investigators from the University of California, Los Angeles, and the University of Washington, Seattle.

Emphasizing an urgent need for “agile healthcare analytics” to enable “disease surveillance in real time,” the first author of the EMR study, Joann G. Elmore, MD, professor in the department of health policy and management at the University of California, Los Angeles, expressed the hope that the approach will “lead to better preparation and the ability to quickly provide warnings and track the next pandemic.”

SOURCE: Basavaraju SV et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1785); Elmore JG et al. J Med Internet Res. 2020;22:e21562).

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

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

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

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

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.