Rheumatology News

As the race to develop rapid testing for COVID-19 expands, the Food and Drug Administration has granted emergency approval for an approach that uses saliva as the primary test biomaterial.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

According to a document provided to the FDA, the Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay is intended for the qualitative detection of nucleic acid from SARS-CoV-2 in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab from individuals suspected of COVID-19 by their health care clinicians. To expand on this assay, Rutgers University–based RUCDR Infinite Biologics developed a saliva collection method in partnership with Spectrum Solutions and Accurate Diagnostic Labs.

The document states that collection of saliva specimens is limited to patients with symptoms of COVID-19 and should be performed in a health care setting under the supervision of a trained health care clinician. Samples are transported for RNA extraction and are tested within 48 hours of collection. In saliva samples obtained from 60 patients evaluated by the researchers, all were in agreement with the presence of COVID-19.

“If shown to be as accurate as nasopharyngeal and oropharyngeal samples, saliva as a biomatrix offers the advantage of not generating aerosols or creating as many respiratory droplets during specimen procurement, therefore decreasing the risk of transmission to the health care worker doing the testing,” said Matthew P. Cheng, MDCM, of the division of infectious diseases at McGill University Health Centre, Montreal, who was not involved in development of the test but who has written about diagnostic testing for the virus.

“Also, it may be easy enough for patients to do saliva self-collection at home. However, it is important to note that SARS-CoV-2 tests on saliva have not yet undergone the more rigorous evaluation of full FDA authorization, and saliva is not a preferred specimen type of the FDA nor the [Centers for Disease Control and Prevention] for respiratory virus testing.”

In a prepared statement, Andrew I. Brooks, PhD, chief operating officer at RUCDR Infinite Biologics, said the saliva collection method enables clinicians to preserve personal protective equipment for use in patient care instead of testing. “We can significantly increase the number of people tested each and every day as self-collection of saliva is quicker and more scalable than swab collections,” he said. “All of this combined will have a tremendous impact on testing in New Jersey and across the United States.”

The tests are currently available to the RWJBarnabas Health network, based in West Orange, N.J., which has partnered with Rutgers University.

dbrunk@mdedge.com

As the race to develop rapid testing for COVID-19 expands, the Food and Drug Administration has granted emergency approval for an approach that uses saliva as the primary test biomaterial.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

According to a document provided to the FDA, the Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay is intended for the qualitative detection of nucleic acid from SARS-CoV-2 in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab from individuals suspected of COVID-19 by their health care clinicians. To expand on this assay, Rutgers University–based RUCDR Infinite Biologics developed a saliva collection method in partnership with Spectrum Solutions and Accurate Diagnostic Labs.

The document states that collection of saliva specimens is limited to patients with symptoms of COVID-19 and should be performed in a health care setting under the supervision of a trained health care clinician. Samples are transported for RNA extraction and are tested within 48 hours of collection. In saliva samples obtained from 60 patients evaluated by the researchers, all were in agreement with the presence of COVID-19.

“If shown to be as accurate as nasopharyngeal and oropharyngeal samples, saliva as a biomatrix offers the advantage of not generating aerosols or creating as many respiratory droplets during specimen procurement, therefore decreasing the risk of transmission to the health care worker doing the testing,” said Matthew P. Cheng, MDCM, of the division of infectious diseases at McGill University Health Centre, Montreal, who was not involved in development of the test but who has written about diagnostic testing for the virus.

“Also, it may be easy enough for patients to do saliva self-collection at home. However, it is important to note that SARS-CoV-2 tests on saliva have not yet undergone the more rigorous evaluation of full FDA authorization, and saliva is not a preferred specimen type of the FDA nor the [Centers for Disease Control and Prevention] for respiratory virus testing.”

In a prepared statement, Andrew I. Brooks, PhD, chief operating officer at RUCDR Infinite Biologics, said the saliva collection method enables clinicians to preserve personal protective equipment for use in patient care instead of testing. “We can significantly increase the number of people tested each and every day as self-collection of saliva is quicker and more scalable than swab collections,” he said. “All of this combined will have a tremendous impact on testing in New Jersey and across the United States.”

The tests are currently available to the RWJBarnabas Health network, based in West Orange, N.J., which has partnered with Rutgers University.

dbrunk@mdedge.com

As the race to develop rapid testing for COVID-19 expands, the Food and Drug Administration has granted emergency approval for an approach that uses saliva as the primary test biomaterial.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

According to a document provided to the FDA, the Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay is intended for the qualitative detection of nucleic acid from SARS-CoV-2 in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab from individuals suspected of COVID-19 by their health care clinicians. To expand on this assay, Rutgers University–based RUCDR Infinite Biologics developed a saliva collection method in partnership with Spectrum Solutions and Accurate Diagnostic Labs.

The document states that collection of saliva specimens is limited to patients with symptoms of COVID-19 and should be performed in a health care setting under the supervision of a trained health care clinician. Samples are transported for RNA extraction and are tested within 48 hours of collection. In saliva samples obtained from 60 patients evaluated by the researchers, all were in agreement with the presence of COVID-19.

“If shown to be as accurate as nasopharyngeal and oropharyngeal samples, saliva as a biomatrix offers the advantage of not generating aerosols or creating as many respiratory droplets during specimen procurement, therefore decreasing the risk of transmission to the health care worker doing the testing,” said Matthew P. Cheng, MDCM, of the division of infectious diseases at McGill University Health Centre, Montreal, who was not involved in development of the test but who has written about diagnostic testing for the virus.

“Also, it may be easy enough for patients to do saliva self-collection at home. However, it is important to note that SARS-CoV-2 tests on saliva have not yet undergone the more rigorous evaluation of full FDA authorization, and saliva is not a preferred specimen type of the FDA nor the [Centers for Disease Control and Prevention] for respiratory virus testing.”

In a prepared statement, Andrew I. Brooks, PhD, chief operating officer at RUCDR Infinite Biologics, said the saliva collection method enables clinicians to preserve personal protective equipment for use in patient care instead of testing. “We can significantly increase the number of people tested each and every day as self-collection of saliva is quicker and more scalable than swab collections,” he said. “All of this combined will have a tremendous impact on testing in New Jersey and across the United States.”

The tests are currently available to the RWJBarnabas Health network, based in West Orange, N.J., which has partnered with Rutgers University.

dbrunk@mdedge.com

Empty shelves that once cradled toilet paper rolls; lines of shoppers, some with masks; waiting 6 feet or at least a shopping cart length apart to get into grocery stores; hazmat-suited workers loading body bags into makeshift mortuaries ... These are the images we have come to associate with the COVID-19 pandemic. But then there also are the graphs and charts, none of them bearing good news. Some are difficult to interpret because they may be missing a key ingredient, such as a scale. Day to day fluctuations in the timeliness of the data points can make valid comparisons impossible. In most cases, it is too early to look at the graphs and hope for the big picture. Whether you are concerned about the stock market or the number of new cases of the virus in your county, you are hoping to see some graphic depiction of a favorable trend.

Richard McMillin/iStock Editorial/Getty Images

We have suddenly learned about the urgency of a process called “flattening the curve.” Are we doing as good a job of flattening as we could be? Are we doing better than France or Spain? Or are we heading toward an Italianesque apocalypse? Who is going to tell us when the flattening is for real and not just a 2- or 3-day statistical aberration?

The curves we are obsessed with today are those showing us new cases and new deaths. But there is another curve that we will need to concentrate on long after the much yearned for flattening of the death curve has been achieved. And we won’t be seeing this curve in four-color graphics on the front page of our newspapers. It is the learning curve, and we want it to be as steep as we can make it without any hint of flattening in the foreseeable future.

We need to learn more about corona-like viruses. Why are some of us more vulnerable? We need to learn more about contagion. Does the 6-foot guideline make any sense? How long are viral particles floating in the air capable of initiating disease? What about air flow and dilution? Can we build a cruise ship or airplane that will be less of a health hazard?

More importantly, we need to learn to be better prepared. Even before the pandemic there have been shortages in intravenous solutions and drugs of critical importance to common diseases. Can we learn how to create reliable and affordable supply chains that allow researchers and developers to make a reasonable profit? Can we relearn to value science? Can we learn to invest more heavily in epidemiology and make it a specialty that attracts our best thinkers and communicators? Then can we elect officials who will share our trust in their recommendations?

Can we do a better job of resolving the tension between those who believe in a strong federal government and those who believe in local autonomy because we are seeing every day that this is an issue of survival, not just coexistence? Can we learn that the globalization that has allowed this viral spread can also be leveraged to beat it into submission?

Over the last half century there has been an unfortunate flattening of the learning curve. Ironically we have seen exponential growth among hi-tech industries that have forced us to keep abreast of new developments. But along with this has been a growing skepticism about value of scientific investigation. It is time we climbed back on that steep learning curve. The view gets better the higher we climb.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

Empty shelves that once cradled toilet paper rolls; lines of shoppers, some with masks; waiting 6 feet or at least a shopping cart length apart to get into grocery stores; hazmat-suited workers loading body bags into makeshift mortuaries ... These are the images we have come to associate with the COVID-19 pandemic. But then there also are the graphs and charts, none of them bearing good news. Some are difficult to interpret because they may be missing a key ingredient, such as a scale. Day to day fluctuations in the timeliness of the data points can make valid comparisons impossible. In most cases, it is too early to look at the graphs and hope for the big picture. Whether you are concerned about the stock market or the number of new cases of the virus in your county, you are hoping to see some graphic depiction of a favorable trend.

Richard McMillin/iStock Editorial/Getty Images

We have suddenly learned about the urgency of a process called “flattening the curve.” Are we doing as good a job of flattening as we could be? Are we doing better than France or Spain? Or are we heading toward an Italianesque apocalypse? Who is going to tell us when the flattening is for real and not just a 2- or 3-day statistical aberration?

The curves we are obsessed with today are those showing us new cases and new deaths. But there is another curve that we will need to concentrate on long after the much yearned for flattening of the death curve has been achieved. And we won’t be seeing this curve in four-color graphics on the front page of our newspapers. It is the learning curve, and we want it to be as steep as we can make it without any hint of flattening in the foreseeable future.

We need to learn more about corona-like viruses. Why are some of us more vulnerable? We need to learn more about contagion. Does the 6-foot guideline make any sense? How long are viral particles floating in the air capable of initiating disease? What about air flow and dilution? Can we build a cruise ship or airplane that will be less of a health hazard?

More importantly, we need to learn to be better prepared. Even before the pandemic there have been shortages in intravenous solutions and drugs of critical importance to common diseases. Can we learn how to create reliable and affordable supply chains that allow researchers and developers to make a reasonable profit? Can we relearn to value science? Can we learn to invest more heavily in epidemiology and make it a specialty that attracts our best thinkers and communicators? Then can we elect officials who will share our trust in their recommendations?

Can we do a better job of resolving the tension between those who believe in a strong federal government and those who believe in local autonomy because we are seeing every day that this is an issue of survival, not just coexistence? Can we learn that the globalization that has allowed this viral spread can also be leveraged to beat it into submission?

Over the last half century there has been an unfortunate flattening of the learning curve. Ironically we have seen exponential growth among hi-tech industries that have forced us to keep abreast of new developments. But along with this has been a growing skepticism about value of scientific investigation. It is time we climbed back on that steep learning curve. The view gets better the higher we climb.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

Empty shelves that once cradled toilet paper rolls; lines of shoppers, some with masks; waiting 6 feet or at least a shopping cart length apart to get into grocery stores; hazmat-suited workers loading body bags into makeshift mortuaries ... These are the images we have come to associate with the COVID-19 pandemic. But then there also are the graphs and charts, none of them bearing good news. Some are difficult to interpret because they may be missing a key ingredient, such as a scale. Day to day fluctuations in the timeliness of the data points can make valid comparisons impossible. In most cases, it is too early to look at the graphs and hope for the big picture. Whether you are concerned about the stock market or the number of new cases of the virus in your county, you are hoping to see some graphic depiction of a favorable trend.

Richard McMillin/iStock Editorial/Getty Images

We have suddenly learned about the urgency of a process called “flattening the curve.” Are we doing as good a job of flattening as we could be? Are we doing better than France or Spain? Or are we heading toward an Italianesque apocalypse? Who is going to tell us when the flattening is for real and not just a 2- or 3-day statistical aberration?

The curves we are obsessed with today are those showing us new cases and new deaths. But there is another curve that we will need to concentrate on long after the much yearned for flattening of the death curve has been achieved. And we won’t be seeing this curve in four-color graphics on the front page of our newspapers. It is the learning curve, and we want it to be as steep as we can make it without any hint of flattening in the foreseeable future.

We need to learn more about corona-like viruses. Why are some of us more vulnerable? We need to learn more about contagion. Does the 6-foot guideline make any sense? How long are viral particles floating in the air capable of initiating disease? What about air flow and dilution? Can we build a cruise ship or airplane that will be less of a health hazard?

More importantly, we need to learn to be better prepared. Even before the pandemic there have been shortages in intravenous solutions and drugs of critical importance to common diseases. Can we learn how to create reliable and affordable supply chains that allow researchers and developers to make a reasonable profit? Can we relearn to value science? Can we learn to invest more heavily in epidemiology and make it a specialty that attracts our best thinkers and communicators? Then can we elect officials who will share our trust in their recommendations?

Can we do a better job of resolving the tension between those who believe in a strong federal government and those who believe in local autonomy because we are seeing every day that this is an issue of survival, not just coexistence? Can we learn that the globalization that has allowed this viral spread can also be leveraged to beat it into submission?

Over the last half century there has been an unfortunate flattening of the learning curve. Ironically we have seen exponential growth among hi-tech industries that have forced us to keep abreast of new developments. But along with this has been a growing skepticism about value of scientific investigation. It is time we climbed back on that steep learning curve. The view gets better the higher we climb.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

If you are anything like me, March 1 came and went as just another first day of the month. Few of us could have imagined that our day-to-day way of life would soon be upended, and our country would be in the midst of the COVID-19 pandemic. While there is considerable anxiety around protecting our individual health, social distancing and the physical isolation that comes from it have cut off a vital source of support for many of our lesbian, gay, bisexual, transgender, and questioning (or queer) (LGBTQ) youth. Shared experiences with other young people like themselves provide these youth with a sense of community that they may not find in their schools, towns, etc.

LGBTQ youth already face increased rates of anxiety and depression compared with their heterosexual and cisgender peers. According to the 2017 Youth Risk Behavior Survey, 63% of LGB youth nationwide reported feeling sad or hopeless compared with 28% of their heterosexual peers. While quarantined at home, many of these youth now are stuck for many more hours per day with families who may not accept them for who they are. Previous research by Ryan et al. shows that LGB adolescents who have higher rates of family rejection are nearly six times more likely to have higher rates of depression and more than eight times more likely to attempt suicide than their peers who come from families with low or no levels of rejection (Pediatrics. 2009 Jan;123[1]:346-52). Going to school for roughly 8 hours a day allows some of these youth an escape from what is otherwise an unpleasant home situation. In addition, educators and other school staff may be among the only allies that a student has in his/her life, and school cancellations remove students from access to these important people.

AJ_Watt/E+

Due to stay-at-home orders and physical distancing measures, lack of in-person access to medical and psychological care can be distressing for many LGBTQ youth. While many practices have been able to convert to audiovisual telemedicine visits, not all of them have the resources or capability to do so. Consequently, LGBTQ youth may have reduced access to support services that help to bolster their social and emotional health. In addition, many trans youth suffer from physical dysphoria that can make it distressing to see themselves on camera doing teletherapy and so they wish to avoid it for this reason.

This is not to say that everything is bleak. LGBTQ youth can also be resilient in times of stress and worry. “The LGBTQ community has a long history of overcoming adversity and utilizing challenges to build an even stronger sense of community. This pandemic will create yet another opportunity for us to highlight existing health disparities and to support our LGBTQ young people in finding creative responses,” said Heather Newby, LCSW, clinical social worker for the GENECIS (GENder Education and Care Interdisciplinary Support) Program at Children’s Medical Center Dallas. In addition, she reported that many LGBTQ advocacy groups have created excellent online support networks and resources to provide nationwide, regional, and local help. By leveraging these youths’ capability for resilience, we are best able to support them during a time of crisis.

During these challenging times, there are a number of resources that LGBTQ youth can turn to while trying to maintain their connection to their peers. First, many local LGBTQ service organizations have moved their in-person support groups to a virtual or online platform. Check with your local service organization to see what they are offering during these times. National organizations, such as Gender Spectrum, continue to have online groups as well that youth can participate in. Second, many virtual mental health helplines, such as those through the Trevor Project, remain staffed should LGBTQ youth need to access their services (1-866-488-7386, plus text and chat). They can be reached 24/7 to help those whose mental health has been affected during this pandemic. Third, youth can continue to stay connected to their friends through means such as Zoom, FaceTime, or other virtual audiovisual tools. Lastly, some youth have taken to meeting in school parking lots, mall parking lots, etc., and staying at least 6 feet apart so that they can still see their friends in person.

While the current times may be challenging, they will pass and we will be able to return to those activities that bring us joy. Do not hesitate to reach out if you need help. As Rainer Maria Rilke once said, “In the difficult, we must have our joys, our happiness, our dreams: There against the depth of this background, they stand out, there for the first time we see how beautiful they are.”
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Dr. Cooper is on Twitter @teendocmbc. Email him at pdnews@mdedge.com.

If you are anything like me, March 1 came and went as just another first day of the month. Few of us could have imagined that our day-to-day way of life would soon be upended, and our country would be in the midst of the COVID-19 pandemic. While there is considerable anxiety around protecting our individual health, social distancing and the physical isolation that comes from it have cut off a vital source of support for many of our lesbian, gay, bisexual, transgender, and questioning (or queer) (LGBTQ) youth. Shared experiences with other young people like themselves provide these youth with a sense of community that they may not find in their schools, towns, etc.

LGBTQ youth already face increased rates of anxiety and depression compared with their heterosexual and cisgender peers. According to the 2017 Youth Risk Behavior Survey, 63% of LGB youth nationwide reported feeling sad or hopeless compared with 28% of their heterosexual peers. While quarantined at home, many of these youth now are stuck for many more hours per day with families who may not accept them for who they are. Previous research by Ryan et al. shows that LGB adolescents who have higher rates of family rejection are nearly six times more likely to have higher rates of depression and more than eight times more likely to attempt suicide than their peers who come from families with low or no levels of rejection (Pediatrics. 2009 Jan;123[1]:346-52). Going to school for roughly 8 hours a day allows some of these youth an escape from what is otherwise an unpleasant home situation. In addition, educators and other school staff may be among the only allies that a student has in his/her life, and school cancellations remove students from access to these important people.

AJ_Watt/E+

Due to stay-at-home orders and physical distancing measures, lack of in-person access to medical and psychological care can be distressing for many LGBTQ youth. While many practices have been able to convert to audiovisual telemedicine visits, not all of them have the resources or capability to do so. Consequently, LGBTQ youth may have reduced access to support services that help to bolster their social and emotional health. In addition, many trans youth suffer from physical dysphoria that can make it distressing to see themselves on camera doing teletherapy and so they wish to avoid it for this reason.

This is not to say that everything is bleak. LGBTQ youth can also be resilient in times of stress and worry. “The LGBTQ community has a long history of overcoming adversity and utilizing challenges to build an even stronger sense of community. This pandemic will create yet another opportunity for us to highlight existing health disparities and to support our LGBTQ young people in finding creative responses,” said Heather Newby, LCSW, clinical social worker for the GENECIS (GENder Education and Care Interdisciplinary Support) Program at Children’s Medical Center Dallas. In addition, she reported that many LGBTQ advocacy groups have created excellent online support networks and resources to provide nationwide, regional, and local help. By leveraging these youths’ capability for resilience, we are best able to support them during a time of crisis.

During these challenging times, there are a number of resources that LGBTQ youth can turn to while trying to maintain their connection to their peers. First, many local LGBTQ service organizations have moved their in-person support groups to a virtual or online platform. Check with your local service organization to see what they are offering during these times. National organizations, such as Gender Spectrum, continue to have online groups as well that youth can participate in. Second, many virtual mental health helplines, such as those through the Trevor Project, remain staffed should LGBTQ youth need to access their services (1-866-488-7386, plus text and chat). They can be reached 24/7 to help those whose mental health has been affected during this pandemic. Third, youth can continue to stay connected to their friends through means such as Zoom, FaceTime, or other virtual audiovisual tools. Lastly, some youth have taken to meeting in school parking lots, mall parking lots, etc., and staying at least 6 feet apart so that they can still see their friends in person.

While the current times may be challenging, they will pass and we will be able to return to those activities that bring us joy. Do not hesitate to reach out if you need help. As Rainer Maria Rilke once said, “In the difficult, we must have our joys, our happiness, our dreams: There against the depth of this background, they stand out, there for the first time we see how beautiful they are.”
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Dr. Cooper is on Twitter @teendocmbc. Email him at pdnews@mdedge.com.

If you are anything like me, March 1 came and went as just another first day of the month. Few of us could have imagined that our day-to-day way of life would soon be upended, and our country would be in the midst of the COVID-19 pandemic. While there is considerable anxiety around protecting our individual health, social distancing and the physical isolation that comes from it have cut off a vital source of support for many of our lesbian, gay, bisexual, transgender, and questioning (or queer) (LGBTQ) youth. Shared experiences with other young people like themselves provide these youth with a sense of community that they may not find in their schools, towns, etc.

LGBTQ youth already face increased rates of anxiety and depression compared with their heterosexual and cisgender peers. According to the 2017 Youth Risk Behavior Survey, 63% of LGB youth nationwide reported feeling sad or hopeless compared with 28% of their heterosexual peers. While quarantined at home, many of these youth now are stuck for many more hours per day with families who may not accept them for who they are. Previous research by Ryan et al. shows that LGB adolescents who have higher rates of family rejection are nearly six times more likely to have higher rates of depression and more than eight times more likely to attempt suicide than their peers who come from families with low or no levels of rejection (Pediatrics. 2009 Jan;123[1]:346-52). Going to school for roughly 8 hours a day allows some of these youth an escape from what is otherwise an unpleasant home situation. In addition, educators and other school staff may be among the only allies that a student has in his/her life, and school cancellations remove students from access to these important people.

AJ_Watt/E+

Due to stay-at-home orders and physical distancing measures, lack of in-person access to medical and psychological care can be distressing for many LGBTQ youth. While many practices have been able to convert to audiovisual telemedicine visits, not all of them have the resources or capability to do so. Consequently, LGBTQ youth may have reduced access to support services that help to bolster their social and emotional health. In addition, many trans youth suffer from physical dysphoria that can make it distressing to see themselves on camera doing teletherapy and so they wish to avoid it for this reason.

This is not to say that everything is bleak. LGBTQ youth can also be resilient in times of stress and worry. “The LGBTQ community has a long history of overcoming adversity and utilizing challenges to build an even stronger sense of community. This pandemic will create yet another opportunity for us to highlight existing health disparities and to support our LGBTQ young people in finding creative responses,” said Heather Newby, LCSW, clinical social worker for the GENECIS (GENder Education and Care Interdisciplinary Support) Program at Children’s Medical Center Dallas. In addition, she reported that many LGBTQ advocacy groups have created excellent online support networks and resources to provide nationwide, regional, and local help. By leveraging these youths’ capability for resilience, we are best able to support them during a time of crisis.

During these challenging times, there are a number of resources that LGBTQ youth can turn to while trying to maintain their connection to their peers. First, many local LGBTQ service organizations have moved their in-person support groups to a virtual or online platform. Check with your local service organization to see what they are offering during these times. National organizations, such as Gender Spectrum, continue to have online groups as well that youth can participate in. Second, many virtual mental health helplines, such as those through the Trevor Project, remain staffed should LGBTQ youth need to access their services (1-866-488-7386, plus text and chat). They can be reached 24/7 to help those whose mental health has been affected during this pandemic. Third, youth can continue to stay connected to their friends through means such as Zoom, FaceTime, or other virtual audiovisual tools. Lastly, some youth have taken to meeting in school parking lots, mall parking lots, etc., and staying at least 6 feet apart so that they can still see their friends in person.

While the current times may be challenging, they will pass and we will be able to return to those activities that bring us joy. Do not hesitate to reach out if you need help. As Rainer Maria Rilke once said, “In the difficult, we must have our joys, our happiness, our dreams: There against the depth of this background, they stand out, there for the first time we see how beautiful they are.”
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas. He has no relevant financial disclosures. Dr. Cooper is on Twitter @teendocmbc. Email him at pdnews@mdedge.com.

As the coronavirus pandemic has swept across America, so have advisories for social distancing. As of April 2, stay-at-home orders had been given in 38 states and parts of 7 more, affecting about 300 million people. Most of these people have been asked to maintain 6 feet of separation to anyone outside their immediate family and to avoid all avoidable contacts.

Typical hospital medicine patients at an academic hospital, however, traditionally receive visits from their hospitalist, an intern, a resident, and sometimes several medical students, pharmacists, and case managers. At University of California, San Diego, Health, many of these visits would occur during Focused Interdisciplinary Team rounds, with providers moving together in close proximity.

Asymptomatic and presymptomatic spread of coronavirus have been documented, which means distancing is a good idea for everyone. The risks of traditional patient visits during the coronavirus pandemic include spread to both patients (at high risk of complications) and staff (taken out of the workforce during surge times). Even if coronavirus were not a risk, visits to isolation rooms consume PPE, which is in short supply.

In response to the pandemic, UCSD Hospital Medicine drafted guidelines for the reduction of patient contacts. Our slide presentations and written guidelines were then distributed to physicians, nurses, pharmacists, and other staff by our pandemic response command center. Key points include the following:

• Target one in-person MD visit per day for stable patients. This means that attending reexaminations of patients seen by residents, nurse practitioners, physician assistants, and so on would not be done for billing or teaching purposes, only when clinically necessary.
• Use phone or video conferencing for follow-up discussions unless direct patient contact is needed.
• Consider skipping daily exams on patients who do not require them, such as patients awaiting placement or stably receiving long courses of antibiotics. Interview them remotely or from the door instead.
• Conduct team rounds, patient discussions, and handoffs with all members 6 feet apart or by telephone or video. Avoid shared work rooms. Substitute video conferences for in-person meetings. Use EMR embedded messaging to reduce face-to-face discussions.
• Check if a patient is ready for a visit before donning PPE to avoid waste.
• Explain to patients that distancing is being conducted to protect them. In our experience, when patients are asked about distancing, they welcome the changes.

We have also considered that most patient visits are generated by nurses and assistants. To increase distancing and reduce PPE waste, we have encouraged nurses and pharmacists to maximize their use of remote communication with patients and to suggest changes to care plans and come up with creative solutions to reduce traffic. We specifically suggested the following changes to routine care:

• Reduce frequency of taking vital signs, such as just daily or as needed, in stable patients (for example, those awaiting placement).
• Reduce checks for alcohol withdrawal and neurologic status as soon as possible, and stop fingersticks in patients with well-controlled diabetes not receiving insulin.
• Substitute less frequently administered medications where appropriate if doing so would reduce room traffic (such as enoxaparin for heparin, ceftriaxone for cefazolin, naproxen for ibuprofen, or patient-controlled analgesia for as needed morphine).
• Place intravenous pumps in halls if needed – luckily, our situation has not required these measures in San Diego.
• Explore the possibility of increased patient self-management (self-dosed insulin or inhalers) where medically appropriate.
• Eliminate food service and janitorial trips to isolation rooms unless requested by registered nurse.

There are clear downsides to medical distancing for hospital medicine patients. Patients might have delayed diagnosis of new conditions or inadequate management of conditions requiring frequent assessment, such as alcohol withdrawal. Opportunities for miscommunication (either patient-provider or provider-provider) may be increased with distancing. Isolation also comes with emotional costs such as stress and feelings of isolation or abandonment. Given the dynamic nature of the pandemic response, we are continually reevaluating our distancing guidelines to administer the safest and most effective hospital care possible as we approach California’s expected peak coronavirus infection period.

Dr. Jenkins is professor and chair of the Patient Safety Committee in the Division of Hospital Medicine at UCSD. Dr. Seymann is clinical professor and vice chief for academic affairs, UCSD division of hospital medicine. Dr. Horman and Dr. Bell are hospitalists and associate professors of medicine at UC San Diego Health.

As the coronavirus pandemic has swept across America, so have advisories for social distancing. As of April 2, stay-at-home orders had been given in 38 states and parts of 7 more, affecting about 300 million people. Most of these people have been asked to maintain 6 feet of separation to anyone outside their immediate family and to avoid all avoidable contacts.

Typical hospital medicine patients at an academic hospital, however, traditionally receive visits from their hospitalist, an intern, a resident, and sometimes several medical students, pharmacists, and case managers. At University of California, San Diego, Health, many of these visits would occur during Focused Interdisciplinary Team rounds, with providers moving together in close proximity.

Asymptomatic and presymptomatic spread of coronavirus have been documented, which means distancing is a good idea for everyone. The risks of traditional patient visits during the coronavirus pandemic include spread to both patients (at high risk of complications) and staff (taken out of the workforce during surge times). Even if coronavirus were not a risk, visits to isolation rooms consume PPE, which is in short supply.

In response to the pandemic, UCSD Hospital Medicine drafted guidelines for the reduction of patient contacts. Our slide presentations and written guidelines were then distributed to physicians, nurses, pharmacists, and other staff by our pandemic response command center. Key points include the following:

• Target one in-person MD visit per day for stable patients. This means that attending reexaminations of patients seen by residents, nurse practitioners, physician assistants, and so on would not be done for billing or teaching purposes, only when clinically necessary.
• Use phone or video conferencing for follow-up discussions unless direct patient contact is needed.
• Consider skipping daily exams on patients who do not require them, such as patients awaiting placement or stably receiving long courses of antibiotics. Interview them remotely or from the door instead.
• Conduct team rounds, patient discussions, and handoffs with all members 6 feet apart or by telephone or video. Avoid shared work rooms. Substitute video conferences for in-person meetings. Use EMR embedded messaging to reduce face-to-face discussions.
• Check if a patient is ready for a visit before donning PPE to avoid waste.
• Explain to patients that distancing is being conducted to protect them. In our experience, when patients are asked about distancing, they welcome the changes.

We have also considered that most patient visits are generated by nurses and assistants. To increase distancing and reduce PPE waste, we have encouraged nurses and pharmacists to maximize their use of remote communication with patients and to suggest changes to care plans and come up with creative solutions to reduce traffic. We specifically suggested the following changes to routine care:

• Reduce frequency of taking vital signs, such as just daily or as needed, in stable patients (for example, those awaiting placement).
• Reduce checks for alcohol withdrawal and neurologic status as soon as possible, and stop fingersticks in patients with well-controlled diabetes not receiving insulin.
• Substitute less frequently administered medications where appropriate if doing so would reduce room traffic (such as enoxaparin for heparin, ceftriaxone for cefazolin, naproxen for ibuprofen, or patient-controlled analgesia for as needed morphine).
• Place intravenous pumps in halls if needed – luckily, our situation has not required these measures in San Diego.
• Explore the possibility of increased patient self-management (self-dosed insulin or inhalers) where medically appropriate.
• Eliminate food service and janitorial trips to isolation rooms unless requested by registered nurse.

There are clear downsides to medical distancing for hospital medicine patients. Patients might have delayed diagnosis of new conditions or inadequate management of conditions requiring frequent assessment, such as alcohol withdrawal. Opportunities for miscommunication (either patient-provider or provider-provider) may be increased with distancing. Isolation also comes with emotional costs such as stress and feelings of isolation or abandonment. Given the dynamic nature of the pandemic response, we are continually reevaluating our distancing guidelines to administer the safest and most effective hospital care possible as we approach California’s expected peak coronavirus infection period.

Dr. Jenkins is professor and chair of the Patient Safety Committee in the Division of Hospital Medicine at UCSD. Dr. Seymann is clinical professor and vice chief for academic affairs, UCSD division of hospital medicine. Dr. Horman and Dr. Bell are hospitalists and associate professors of medicine at UC San Diego Health.

As the coronavirus pandemic has swept across America, so have advisories for social distancing. As of April 2, stay-at-home orders had been given in 38 states and parts of 7 more, affecting about 300 million people. Most of these people have been asked to maintain 6 feet of separation to anyone outside their immediate family and to avoid all avoidable contacts.

Typical hospital medicine patients at an academic hospital, however, traditionally receive visits from their hospitalist, an intern, a resident, and sometimes several medical students, pharmacists, and case managers. At University of California, San Diego, Health, many of these visits would occur during Focused Interdisciplinary Team rounds, with providers moving together in close proximity.

Asymptomatic and presymptomatic spread of coronavirus have been documented, which means distancing is a good idea for everyone. The risks of traditional patient visits during the coronavirus pandemic include spread to both patients (at high risk of complications) and staff (taken out of the workforce during surge times). Even if coronavirus were not a risk, visits to isolation rooms consume PPE, which is in short supply.

In response to the pandemic, UCSD Hospital Medicine drafted guidelines for the reduction of patient contacts. Our slide presentations and written guidelines were then distributed to physicians, nurses, pharmacists, and other staff by our pandemic response command center. Key points include the following:

• Target one in-person MD visit per day for stable patients. This means that attending reexaminations of patients seen by residents, nurse practitioners, physician assistants, and so on would not be done for billing or teaching purposes, only when clinically necessary.
• Use phone or video conferencing for follow-up discussions unless direct patient contact is needed.
• Consider skipping daily exams on patients who do not require them, such as patients awaiting placement or stably receiving long courses of antibiotics. Interview them remotely or from the door instead.
• Conduct team rounds, patient discussions, and handoffs with all members 6 feet apart or by telephone or video. Avoid shared work rooms. Substitute video conferences for in-person meetings. Use EMR embedded messaging to reduce face-to-face discussions.
• Check if a patient is ready for a visit before donning PPE to avoid waste.
• Explain to patients that distancing is being conducted to protect them. In our experience, when patients are asked about distancing, they welcome the changes.

We have also considered that most patient visits are generated by nurses and assistants. To increase distancing and reduce PPE waste, we have encouraged nurses and pharmacists to maximize their use of remote communication with patients and to suggest changes to care plans and come up with creative solutions to reduce traffic. We specifically suggested the following changes to routine care:

• Reduce frequency of taking vital signs, such as just daily or as needed, in stable patients (for example, those awaiting placement).
• Reduce checks for alcohol withdrawal and neurologic status as soon as possible, and stop fingersticks in patients with well-controlled diabetes not receiving insulin.
• Substitute less frequently administered medications where appropriate if doing so would reduce room traffic (such as enoxaparin for heparin, ceftriaxone for cefazolin, naproxen for ibuprofen, or patient-controlled analgesia for as needed morphine).
• Place intravenous pumps in halls if needed – luckily, our situation has not required these measures in San Diego.
• Explore the possibility of increased patient self-management (self-dosed insulin or inhalers) where medically appropriate.
• Eliminate food service and janitorial trips to isolation rooms unless requested by registered nurse.

There are clear downsides to medical distancing for hospital medicine patients. Patients might have delayed diagnosis of new conditions or inadequate management of conditions requiring frequent assessment, such as alcohol withdrawal. Opportunities for miscommunication (either patient-provider or provider-provider) may be increased with distancing. Isolation also comes with emotional costs such as stress and feelings of isolation or abandonment. Given the dynamic nature of the pandemic response, we are continually reevaluating our distancing guidelines to administer the safest and most effective hospital care possible as we approach California’s expected peak coronavirus infection period.

Dr. Jenkins is professor and chair of the Patient Safety Committee in the Division of Hospital Medicine at UCSD. Dr. Seymann is clinical professor and vice chief for academic affairs, UCSD division of hospital medicine. Dr. Horman and Dr. Bell are hospitalists and associate professors of medicine at UC San Diego Health.

E-consults were highly useful, with more than 80% of them resulting in an avoided visit to a specialist, in a study of e-consult use at a large health system.

Studies have shown that e-consults increase access to specialist care and primary care physician (PCP) education, according to research published in the Annals of Internal Medicine (2020. Apr 14. doi: 10.7326/M19-3852) by Salman Ahmed, MD, and colleagues.

These resources are already being frequently used by physicians, but more often by general internists and hospitalists than by subspecialists, according to a recent survey by the American College of Physicians. That survey found that 42% of its respondents are using e-consults and that subspecialists’ use is less common primarily because of the lack of access to e-consult technology.

What hasn’t been widely researched are the effects of large-scale e-consult programs, said Dr. Ahmed, who is associate physician in the renal division at Brigham and Women’s Hospital, Boston, in an interview.

For frontline providers such as PCPs, e-consults are a way to quickly seek out answers to clinical questions from specialists. In turn, the specialist can help a wider pool of participants, he noted.

The findings of Dr. Ahmed’s study, which included several academic centers and hospitals affiliated with Partners HealthCare System, a nonprofit network in eastern Massachusetts that includes Brigham and Women’s Hospital, used several metrics to analyze the appropriateness and utility of e-consults across a range of specialties. An e-consult was considered useful if it resulted in the avoidance of a visit to a specialist, which was defined as the absence of an in-person visit to the type of specialist consulted electronically for 120 days. An e-consult was considered appropriate if it met the following four criteria.

• It could not be answered by referring to society guidelines or widely available, evidence-based summary sources.
• It did not seek logistic information, such as where to have a specific laboratory test done.
• It did not include a question of high urgency.
• The medical complexity of the clinical situation was not substantial enough to warrant an in-person consultation.

The investigators examined e-consult inquiries to mostly physician health care providers in five specialties – hematology, infectious disease, dermatology, rheumatology, and psychiatry – over a year.
 

High rates of appropriateness

The search spanned 6,512 eligible e-consults from 1,096 referring providers to 121 specialist consultants. Narrowing their search to 741 records with complete data, the investigators found that 70.2% of these consults met the criteria for appropriateness. In an analysis of four reviewers blinded to each other’s results, raters agreed on the appropriateness of 94% of e-consults.

Across specialties, more than 81% of e-consults were associated with avoided in-person visits.

The reasons for most e-consults were to seek answers to questions about diagnosis, therapeutics, or patient inquiries, or to request further education by PCPs.

“Across all specialties, the most common reasons an e-consult was not considered appropriate were failing the point-of-care resource test and asking a question of inappropriately high complexity,” the authors summarized.

Physicians and PCPs from tertiary care practices made up the majority of referring providers, with turnaround time for consults averaging 24 hours across specialties.

Rates of appropriateness, content, patient demographics, and timeliness of e-consult responses varied among the four specialties. Those with high avoidance of visits rates tended to have high appropriateness rates, indicating that some specialties may be more conducive to e-consults than others, the authors noted. Psychiatry and hematology had the highest proportion of appropriate e-consults (77.9% and 73.3% respectively). Rheumatology had the lowest proportion of appropriate e-consults and one of the lowest rates of avoided in-person visits, and dermatology had the lowest rate of avoided in-person visits, at 61.9%.

The majority (93%) of e-consults sought in psychiatry were therapy related, whereas 88.4% of the e-consult questions in rheumatology related to diagnosis.

“Questions about diagnosis were less likely to be answerable via e-consult, which suggests that to provide diagnoses, consultants may wish to engage with the patient directly,” Dr. Ahmed said in an interview.

Infectious disease specialists seemed to be the fastest responders, with nearly 90% of their consultations having been answered within a day. Dermatology specialists had the distinction of having the youngest e-consult patients (mean age, 38.6 years).
 

PCPs weigh in on results

Physicians said in interviews that the study data reflects their own positive experiences with e-consults.

“Although I don’t always think [an e-consult] is able to fully prevent the specialist visit, it does allow the specialist to provide recommendations for work-up that can be done prior to the specialist visit,” said Santina Wheat MD, a family physician at Erie Family Health Center in Chicago. This reduces the time in which the consult is placed to when effective treatment can take place.

Patients who may have to wait months or even years to see a specialty doctor, benefit from e-consults, said Dr. Wheat, who is also a member of the editorial advisory board of Family Practice News. “As part of an organization that does e-consults to another hospital with a different electronic medical record, the e-consult increases the likelihood that all of the clinical information reaches the specialists and prevents tests from being repeated.”

Starting an e-consult may also increase the likelihood that the patient quickly sees a specialist at the contracted hospital, she added.

Sarah G. Candler, MD, said in an interview that she also sees e-consults as an essential tool. “When patients present with rare, complex, or atypical pictures, I find it helpful to have specialists weigh in. The e-consult helps me ensure that I work to the top of my abilities as an internist,” said Dr. Candler, who is practice medical director and physician director of academic relations at Iora Primary Care, Northside Clinic, Houston. However, she did not agree with the study’s avoided in-person visits metric for assessing utility.

“In some cases, the end result of an e-consult is a referral for an in-person evaluation, and the role of the e-consult is to ensure that I have done my due diligence as a primary care doctor asking the correct questions, getting the appropriate work-up completed, and referring to the appropriate specialty for next steps, when necessary,” noted Dr. Candler, who also serves on the editorial advisory board of Internal Medicine News.
 

Financial considerations

The study’s authors suggested taking a closer look at standardizing payment for the use of e-consults and developing appropriateness criteria for them.

Health systems could use such criteria to study what makes an e-consult useful and how to best utilize this tool, Dr. Ahmed said in an interview.

“Compensation models that promote high-quality, effective, and efficient e-consults are needed to reinforce the ability of health systems to optimize the mix of e-consults and in-person visits,” Dr. Ahmed and colleagues suggested.

Because not all patient care requires e-consults, the model makes the most sense in practices that already participate in value-based payment programs. In these types of programs, the cost can be shared according to the variable risk and patient need for the service, Dr. Candler explained.

“I have been fortunate to work in two different systems that function in this way, which means that e-consults have been readily available and encouraged-both to improve patient care and decrease overall cost by decreasing unnecessary testing or specialist referral,” she said.

Dr. Wheat said that the managed care organization affiliated with her practice seems to be saving money with e-consults, as it decreases the need to pay for specialist visits in some instances and for repeated work-ups.
 

Future studies

The study’s cohort represented just one large health care system with a shared electronic health record. “Single-system descriptive studies, such as that of Ahmed and colleagues, are particularly useful for local evaluation and quality improvement efforts,” Varsha G. Vimalananda, MD, and B. Graeme Fincke, MD, both of the Center for Healthcare Organization and Implementation Research at Bedford (Mass.) Veterans Affairs Hospital, wrote in a related editorial.

“However, we need innovative approaches to evaluation that estimate the effect of e-consults on quality and cost of care across health care systems and over time. Implementation studies can help to identify key contributors to success,” the editorialists wrote.

One of the study authors, reported receiving personal fees from Bayer outside the submitted work. The other authors of the paper and the authors of the editorial reported no conflicts of interest. Dr. Candler said her employer contracts with an e-consult service, but that she is not compensated for use of the service. She is also a coeditor of Annals of Internal Medicine’s blog, “Fresh Look.”

SOURCE: Ahmed S et al. Ann Intern Med. 2020 Apr 14. doi: 10.7326/M19-3852.

E-consults were highly useful, with more than 80% of them resulting in an avoided visit to a specialist, in a study of e-consult use at a large health system.

Studies have shown that e-consults increase access to specialist care and primary care physician (PCP) education, according to research published in the Annals of Internal Medicine (2020. Apr 14. doi: 10.7326/M19-3852) by Salman Ahmed, MD, and colleagues.

These resources are already being frequently used by physicians, but more often by general internists and hospitalists than by subspecialists, according to a recent survey by the American College of Physicians. That survey found that 42% of its respondents are using e-consults and that subspecialists’ use is less common primarily because of the lack of access to e-consult technology.

What hasn’t been widely researched are the effects of large-scale e-consult programs, said Dr. Ahmed, who is associate physician in the renal division at Brigham and Women’s Hospital, Boston, in an interview.

For frontline providers such as PCPs, e-consults are a way to quickly seek out answers to clinical questions from specialists. In turn, the specialist can help a wider pool of participants, he noted.

The findings of Dr. Ahmed’s study, which included several academic centers and hospitals affiliated with Partners HealthCare System, a nonprofit network in eastern Massachusetts that includes Brigham and Women’s Hospital, used several metrics to analyze the appropriateness and utility of e-consults across a range of specialties. An e-consult was considered useful if it resulted in the avoidance of a visit to a specialist, which was defined as the absence of an in-person visit to the type of specialist consulted electronically for 120 days. An e-consult was considered appropriate if it met the following four criteria.

• It could not be answered by referring to society guidelines or widely available, evidence-based summary sources.
• It did not seek logistic information, such as where to have a specific laboratory test done.
• It did not include a question of high urgency.
• The medical complexity of the clinical situation was not substantial enough to warrant an in-person consultation.

The investigators examined e-consult inquiries to mostly physician health care providers in five specialties – hematology, infectious disease, dermatology, rheumatology, and psychiatry – over a year.
 

High rates of appropriateness

The search spanned 6,512 eligible e-consults from 1,096 referring providers to 121 specialist consultants. Narrowing their search to 741 records with complete data, the investigators found that 70.2% of these consults met the criteria for appropriateness. In an analysis of four reviewers blinded to each other’s results, raters agreed on the appropriateness of 94% of e-consults.

Across specialties, more than 81% of e-consults were associated with avoided in-person visits.

The reasons for most e-consults were to seek answers to questions about diagnosis, therapeutics, or patient inquiries, or to request further education by PCPs.

“Across all specialties, the most common reasons an e-consult was not considered appropriate were failing the point-of-care resource test and asking a question of inappropriately high complexity,” the authors summarized.

Physicians and PCPs from tertiary care practices made up the majority of referring providers, with turnaround time for consults averaging 24 hours across specialties.

Rates of appropriateness, content, patient demographics, and timeliness of e-consult responses varied among the four specialties. Those with high avoidance of visits rates tended to have high appropriateness rates, indicating that some specialties may be more conducive to e-consults than others, the authors noted. Psychiatry and hematology had the highest proportion of appropriate e-consults (77.9% and 73.3% respectively). Rheumatology had the lowest proportion of appropriate e-consults and one of the lowest rates of avoided in-person visits, and dermatology had the lowest rate of avoided in-person visits, at 61.9%.

The majority (93%) of e-consults sought in psychiatry were therapy related, whereas 88.4% of the e-consult questions in rheumatology related to diagnosis.

“Questions about diagnosis were less likely to be answerable via e-consult, which suggests that to provide diagnoses, consultants may wish to engage with the patient directly,” Dr. Ahmed said in an interview.

Infectious disease specialists seemed to be the fastest responders, with nearly 90% of their consultations having been answered within a day. Dermatology specialists had the distinction of having the youngest e-consult patients (mean age, 38.6 years).
 

PCPs weigh in on results

Physicians said in interviews that the study data reflects their own positive experiences with e-consults.

“Although I don’t always think [an e-consult] is able to fully prevent the specialist visit, it does allow the specialist to provide recommendations for work-up that can be done prior to the specialist visit,” said Santina Wheat MD, a family physician at Erie Family Health Center in Chicago. This reduces the time in which the consult is placed to when effective treatment can take place.

Patients who may have to wait months or even years to see a specialty doctor, benefit from e-consults, said Dr. Wheat, who is also a member of the editorial advisory board of Family Practice News. “As part of an organization that does e-consults to another hospital with a different electronic medical record, the e-consult increases the likelihood that all of the clinical information reaches the specialists and prevents tests from being repeated.”

Starting an e-consult may also increase the likelihood that the patient quickly sees a specialist at the contracted hospital, she added.

Sarah G. Candler, MD, said in an interview that she also sees e-consults as an essential tool. “When patients present with rare, complex, or atypical pictures, I find it helpful to have specialists weigh in. The e-consult helps me ensure that I work to the top of my abilities as an internist,” said Dr. Candler, who is practice medical director and physician director of academic relations at Iora Primary Care, Northside Clinic, Houston. However, she did not agree with the study’s avoided in-person visits metric for assessing utility.

“In some cases, the end result of an e-consult is a referral for an in-person evaluation, and the role of the e-consult is to ensure that I have done my due diligence as a primary care doctor asking the correct questions, getting the appropriate work-up completed, and referring to the appropriate specialty for next steps, when necessary,” noted Dr. Candler, who also serves on the editorial advisory board of Internal Medicine News.
 

Financial considerations

The study’s authors suggested taking a closer look at standardizing payment for the use of e-consults and developing appropriateness criteria for them.

Health systems could use such criteria to study what makes an e-consult useful and how to best utilize this tool, Dr. Ahmed said in an interview.

“Compensation models that promote high-quality, effective, and efficient e-consults are needed to reinforce the ability of health systems to optimize the mix of e-consults and in-person visits,” Dr. Ahmed and colleagues suggested.

Because not all patient care requires e-consults, the model makes the most sense in practices that already participate in value-based payment programs. In these types of programs, the cost can be shared according to the variable risk and patient need for the service, Dr. Candler explained.

“I have been fortunate to work in two different systems that function in this way, which means that e-consults have been readily available and encouraged-both to improve patient care and decrease overall cost by decreasing unnecessary testing or specialist referral,” she said.

Dr. Wheat said that the managed care organization affiliated with her practice seems to be saving money with e-consults, as it decreases the need to pay for specialist visits in some instances and for repeated work-ups.
 

Future studies

The study’s cohort represented just one large health care system with a shared electronic health record. “Single-system descriptive studies, such as that of Ahmed and colleagues, are particularly useful for local evaluation and quality improvement efforts,” Varsha G. Vimalananda, MD, and B. Graeme Fincke, MD, both of the Center for Healthcare Organization and Implementation Research at Bedford (Mass.) Veterans Affairs Hospital, wrote in a related editorial.

“However, we need innovative approaches to evaluation that estimate the effect of e-consults on quality and cost of care across health care systems and over time. Implementation studies can help to identify key contributors to success,” the editorialists wrote.

One of the study authors, reported receiving personal fees from Bayer outside the submitted work. The other authors of the paper and the authors of the editorial reported no conflicts of interest. Dr. Candler said her employer contracts with an e-consult service, but that she is not compensated for use of the service. She is also a coeditor of Annals of Internal Medicine’s blog, “Fresh Look.”

SOURCE: Ahmed S et al. Ann Intern Med. 2020 Apr 14. doi: 10.7326/M19-3852.

E-consults were highly useful, with more than 80% of them resulting in an avoided visit to a specialist, in a study of e-consult use at a large health system.

Studies have shown that e-consults increase access to specialist care and primary care physician (PCP) education, according to research published in the Annals of Internal Medicine (2020. Apr 14. doi: 10.7326/M19-3852) by Salman Ahmed, MD, and colleagues.

These resources are already being frequently used by physicians, but more often by general internists and hospitalists than by subspecialists, according to a recent survey by the American College of Physicians. That survey found that 42% of its respondents are using e-consults and that subspecialists’ use is less common primarily because of the lack of access to e-consult technology.

What hasn’t been widely researched are the effects of large-scale e-consult programs, said Dr. Ahmed, who is associate physician in the renal division at Brigham and Women’s Hospital, Boston, in an interview.

For frontline providers such as PCPs, e-consults are a way to quickly seek out answers to clinical questions from specialists. In turn, the specialist can help a wider pool of participants, he noted.

The findings of Dr. Ahmed’s study, which included several academic centers and hospitals affiliated with Partners HealthCare System, a nonprofit network in eastern Massachusetts that includes Brigham and Women’s Hospital, used several metrics to analyze the appropriateness and utility of e-consults across a range of specialties. An e-consult was considered useful if it resulted in the avoidance of a visit to a specialist, which was defined as the absence of an in-person visit to the type of specialist consulted electronically for 120 days. An e-consult was considered appropriate if it met the following four criteria.

• It could not be answered by referring to society guidelines or widely available, evidence-based summary sources.
• It did not seek logistic information, such as where to have a specific laboratory test done.
• It did not include a question of high urgency.
• The medical complexity of the clinical situation was not substantial enough to warrant an in-person consultation.

The investigators examined e-consult inquiries to mostly physician health care providers in five specialties – hematology, infectious disease, dermatology, rheumatology, and psychiatry – over a year.
 

High rates of appropriateness

The search spanned 6,512 eligible e-consults from 1,096 referring providers to 121 specialist consultants. Narrowing their search to 741 records with complete data, the investigators found that 70.2% of these consults met the criteria for appropriateness. In an analysis of four reviewers blinded to each other’s results, raters agreed on the appropriateness of 94% of e-consults.

Across specialties, more than 81% of e-consults were associated with avoided in-person visits.

The reasons for most e-consults were to seek answers to questions about diagnosis, therapeutics, or patient inquiries, or to request further education by PCPs.

“Across all specialties, the most common reasons an e-consult was not considered appropriate were failing the point-of-care resource test and asking a question of inappropriately high complexity,” the authors summarized.

Physicians and PCPs from tertiary care practices made up the majority of referring providers, with turnaround time for consults averaging 24 hours across specialties.

Rates of appropriateness, content, patient demographics, and timeliness of e-consult responses varied among the four specialties. Those with high avoidance of visits rates tended to have high appropriateness rates, indicating that some specialties may be more conducive to e-consults than others, the authors noted. Psychiatry and hematology had the highest proportion of appropriate e-consults (77.9% and 73.3% respectively). Rheumatology had the lowest proportion of appropriate e-consults and one of the lowest rates of avoided in-person visits, and dermatology had the lowest rate of avoided in-person visits, at 61.9%.

The majority (93%) of e-consults sought in psychiatry were therapy related, whereas 88.4% of the e-consult questions in rheumatology related to diagnosis.

“Questions about diagnosis were less likely to be answerable via e-consult, which suggests that to provide diagnoses, consultants may wish to engage with the patient directly,” Dr. Ahmed said in an interview.

Infectious disease specialists seemed to be the fastest responders, with nearly 90% of their consultations having been answered within a day. Dermatology specialists had the distinction of having the youngest e-consult patients (mean age, 38.6 years).
 

PCPs weigh in on results

Physicians said in interviews that the study data reflects their own positive experiences with e-consults.

“Although I don’t always think [an e-consult] is able to fully prevent the specialist visit, it does allow the specialist to provide recommendations for work-up that can be done prior to the specialist visit,” said Santina Wheat MD, a family physician at Erie Family Health Center in Chicago. This reduces the time in which the consult is placed to when effective treatment can take place.

Patients who may have to wait months or even years to see a specialty doctor, benefit from e-consults, said Dr. Wheat, who is also a member of the editorial advisory board of Family Practice News. “As part of an organization that does e-consults to another hospital with a different electronic medical record, the e-consult increases the likelihood that all of the clinical information reaches the specialists and prevents tests from being repeated.”

Starting an e-consult may also increase the likelihood that the patient quickly sees a specialist at the contracted hospital, she added.

Sarah G. Candler, MD, said in an interview that she also sees e-consults as an essential tool. “When patients present with rare, complex, or atypical pictures, I find it helpful to have specialists weigh in. The e-consult helps me ensure that I work to the top of my abilities as an internist,” said Dr. Candler, who is practice medical director and physician director of academic relations at Iora Primary Care, Northside Clinic, Houston. However, she did not agree with the study’s avoided in-person visits metric for assessing utility.

“In some cases, the end result of an e-consult is a referral for an in-person evaluation, and the role of the e-consult is to ensure that I have done my due diligence as a primary care doctor asking the correct questions, getting the appropriate work-up completed, and referring to the appropriate specialty for next steps, when necessary,” noted Dr. Candler, who also serves on the editorial advisory board of Internal Medicine News.
 

Financial considerations

The study’s authors suggested taking a closer look at standardizing payment for the use of e-consults and developing appropriateness criteria for them.

Health systems could use such criteria to study what makes an e-consult useful and how to best utilize this tool, Dr. Ahmed said in an interview.

“Compensation models that promote high-quality, effective, and efficient e-consults are needed to reinforce the ability of health systems to optimize the mix of e-consults and in-person visits,” Dr. Ahmed and colleagues suggested.

Because not all patient care requires e-consults, the model makes the most sense in practices that already participate in value-based payment programs. In these types of programs, the cost can be shared according to the variable risk and patient need for the service, Dr. Candler explained.

“I have been fortunate to work in two different systems that function in this way, which means that e-consults have been readily available and encouraged-both to improve patient care and decrease overall cost by decreasing unnecessary testing or specialist referral,” she said.

Dr. Wheat said that the managed care organization affiliated with her practice seems to be saving money with e-consults, as it decreases the need to pay for specialist visits in some instances and for repeated work-ups.
 

Future studies

The study’s cohort represented just one large health care system with a shared electronic health record. “Single-system descriptive studies, such as that of Ahmed and colleagues, are particularly useful for local evaluation and quality improvement efforts,” Varsha G. Vimalananda, MD, and B. Graeme Fincke, MD, both of the Center for Healthcare Organization and Implementation Research at Bedford (Mass.) Veterans Affairs Hospital, wrote in a related editorial.

“However, we need innovative approaches to evaluation that estimate the effect of e-consults on quality and cost of care across health care systems and over time. Implementation studies can help to identify key contributors to success,” the editorialists wrote.

One of the study authors, reported receiving personal fees from Bayer outside the submitted work. The other authors of the paper and the authors of the editorial reported no conflicts of interest. Dr. Candler said her employer contracts with an e-consult service, but that she is not compensated for use of the service. She is also a coeditor of Annals of Internal Medicine’s blog, “Fresh Look.”

SOURCE: Ahmed S et al. Ann Intern Med. 2020 Apr 14. doi: 10.7326/M19-3852.

Children with overweight or obese body mass index measures at preschool age were significantly more likely than were normal weight children to suffer upper- and lower-limb fractures before age 15 years, according to data from almost 470,000 children.

Previous studies of adults have shown associations between obesity and fractures, but the impact of higher BMI at preschool age on fracture incidence later in childhood has not been explored, according to Jennifer C.E. Lane, MD, of the University of Oxford (England), and colleagues. “A focused study of the association between preschool obesity and fracture risk offers the opportunity to better understand the impact of obesity in early life,” they wrote in the Journal of Bone and Mineral Research.

The researchers reviewed data from 466,997 children at 296 primary care centers using the Information System for Research in Primary Care, a Spanish national database, for the years 2003-2013. The children were assessed starting at age 4 years and followed until age 15 years or until they left the region or died, or until the study period ended, on Dec. 31, 2016. The average follow-up time was 4.9 years, and 49% of the children were girls. BMI categories were determined via the World Health Organization growth standards for calculating age- and sex-specific BMI z scores, and the categories were defined as underweight (< −2 BMI z score), normal weight (−2 to +2 BMI z score), overweight (> +2 BMI z score), and obese (> +3 BMI z score).

Overall, children with a BMI in the overweight or obese ranges at first assessment were significantly more likely than were their normal weight counterparts to suffer lower-limb fractures (adjusted hazard ratios, 1.42 and 1.74, respectively) and upper-limb fractures (aHRs, 1.10 and 1.19, respectively) during the follow-up period.

The total incidence of fractures during childhood for those in the study who were underweight, normal weight, overweight, or obese, was 9.20%, 10.06%, 11.28%, and 13.05% respectively.

In a secondary analysis, fracture risk varied by anatomic location and reflected previous findings showing an increased risk of distal limb fractures associated with high BMI, the researchers said.

The findings were limited by several factors, including the smaller-than-average proportion of children with overweight or obese BMI measures, the imprecise nature of the BMI z score as a predictor of obesity in children, and the lack of data on sports, medical issues, and general activity levels, the researchers noted.

However, the results were strengthened by the population-based sample and long-term follow-up, and the work “suggests that interventions to treat obesity in early childhood could have benefits for the primary or secondary prevention of fractures later in childhood, especially in the prevention of fractures within the forearm and hand or foot and ankle,” the authors concluded.

The study was supported in part by the NIHR Biomedical Research Centre, Oxford, and La Marató de TV3 Foundation. Dr. Lane disclosed funding from a Versus Arthritis Clinical Research Fellowship but had no financial conflicts to disclose. Some authors reported relationships with numerous pharmaceutical firms.

SOURCE: Lane JCE et al. J Bone Miner Res. 2020 Apr 7. doi: 10.1002/jbmr.3984

Children with overweight or obese body mass index measures at preschool age were significantly more likely than were normal weight children to suffer upper- and lower-limb fractures before age 15 years, according to data from almost 470,000 children.

Previous studies of adults have shown associations between obesity and fractures, but the impact of higher BMI at preschool age on fracture incidence later in childhood has not been explored, according to Jennifer C.E. Lane, MD, of the University of Oxford (England), and colleagues. “A focused study of the association between preschool obesity and fracture risk offers the opportunity to better understand the impact of obesity in early life,” they wrote in the Journal of Bone and Mineral Research.

The researchers reviewed data from 466,997 children at 296 primary care centers using the Information System for Research in Primary Care, a Spanish national database, for the years 2003-2013. The children were assessed starting at age 4 years and followed until age 15 years or until they left the region or died, or until the study period ended, on Dec. 31, 2016. The average follow-up time was 4.9 years, and 49% of the children were girls. BMI categories were determined via the World Health Organization growth standards for calculating age- and sex-specific BMI z scores, and the categories were defined as underweight (< −2 BMI z score), normal weight (−2 to +2 BMI z score), overweight (> +2 BMI z score), and obese (> +3 BMI z score).

Overall, children with a BMI in the overweight or obese ranges at first assessment were significantly more likely than were their normal weight counterparts to suffer lower-limb fractures (adjusted hazard ratios, 1.42 and 1.74, respectively) and upper-limb fractures (aHRs, 1.10 and 1.19, respectively) during the follow-up period.

The total incidence of fractures during childhood for those in the study who were underweight, normal weight, overweight, or obese, was 9.20%, 10.06%, 11.28%, and 13.05% respectively.

In a secondary analysis, fracture risk varied by anatomic location and reflected previous findings showing an increased risk of distal limb fractures associated with high BMI, the researchers said.

The findings were limited by several factors, including the smaller-than-average proportion of children with overweight or obese BMI measures, the imprecise nature of the BMI z score as a predictor of obesity in children, and the lack of data on sports, medical issues, and general activity levels, the researchers noted.

However, the results were strengthened by the population-based sample and long-term follow-up, and the work “suggests that interventions to treat obesity in early childhood could have benefits for the primary or secondary prevention of fractures later in childhood, especially in the prevention of fractures within the forearm and hand or foot and ankle,” the authors concluded.

The study was supported in part by the NIHR Biomedical Research Centre, Oxford, and La Marató de TV3 Foundation. Dr. Lane disclosed funding from a Versus Arthritis Clinical Research Fellowship but had no financial conflicts to disclose. Some authors reported relationships with numerous pharmaceutical firms.

SOURCE: Lane JCE et al. J Bone Miner Res. 2020 Apr 7. doi: 10.1002/jbmr.3984

Children with overweight or obese body mass index measures at preschool age were significantly more likely than were normal weight children to suffer upper- and lower-limb fractures before age 15 years, according to data from almost 470,000 children.

Previous studies of adults have shown associations between obesity and fractures, but the impact of higher BMI at preschool age on fracture incidence later in childhood has not been explored, according to Jennifer C.E. Lane, MD, of the University of Oxford (England), and colleagues. “A focused study of the association between preschool obesity and fracture risk offers the opportunity to better understand the impact of obesity in early life,” they wrote in the Journal of Bone and Mineral Research.

The researchers reviewed data from 466,997 children at 296 primary care centers using the Information System for Research in Primary Care, a Spanish national database, for the years 2003-2013. The children were assessed starting at age 4 years and followed until age 15 years or until they left the region or died, or until the study period ended, on Dec. 31, 2016. The average follow-up time was 4.9 years, and 49% of the children were girls. BMI categories were determined via the World Health Organization growth standards for calculating age- and sex-specific BMI z scores, and the categories were defined as underweight (< −2 BMI z score), normal weight (−2 to +2 BMI z score), overweight (> +2 BMI z score), and obese (> +3 BMI z score).

Overall, children with a BMI in the overweight or obese ranges at first assessment were significantly more likely than were their normal weight counterparts to suffer lower-limb fractures (adjusted hazard ratios, 1.42 and 1.74, respectively) and upper-limb fractures (aHRs, 1.10 and 1.19, respectively) during the follow-up period.

The total incidence of fractures during childhood for those in the study who were underweight, normal weight, overweight, or obese, was 9.20%, 10.06%, 11.28%, and 13.05% respectively.

In a secondary analysis, fracture risk varied by anatomic location and reflected previous findings showing an increased risk of distal limb fractures associated with high BMI, the researchers said.

The findings were limited by several factors, including the smaller-than-average proportion of children with overweight or obese BMI measures, the imprecise nature of the BMI z score as a predictor of obesity in children, and the lack of data on sports, medical issues, and general activity levels, the researchers noted.

However, the results were strengthened by the population-based sample and long-term follow-up, and the work “suggests that interventions to treat obesity in early childhood could have benefits for the primary or secondary prevention of fractures later in childhood, especially in the prevention of fractures within the forearm and hand or foot and ankle,” the authors concluded.

The study was supported in part by the NIHR Biomedical Research Centre, Oxford, and La Marató de TV3 Foundation. Dr. Lane disclosed funding from a Versus Arthritis Clinical Research Fellowship but had no financial conflicts to disclose. Some authors reported relationships with numerous pharmaceutical firms.

SOURCE: Lane JCE et al. J Bone Miner Res. 2020 Apr 7. doi: 10.1002/jbmr.3984

COVID-19 infection in patients with type 2 diabetes is associated with a greater increase in inflammatory and coagulation markers, compared with COVID-19 patients without diabetes, according to preliminary findings from a retrospective analysis of COVID-19 patients in Wuhan, China.

The results, though preliminary, could help explain why patients with diabetes and COVID-19 are at greater risk for more severe disease and death.

The results also suggest that more severe disease in patients with diabetes may be the result of a cytokine storm, in which the patient’s immune system overreacts to the virus and inflicts collateral damage on its own organs, according to Herbert I. Rettinger, MD, a clinical endocrinologist in Orange County, Calif., and member of the editorial advisory board for Clinical Endocrinology News. “Understanding the mechanism might help us understand the best way to treat,” COVID-19 in patients with diabetes, he said in an interview.

Dr. Rettinger, who was not involved in the research, noted that the study included only 24 patients with diabetes. Nevertheless, the finding of heightened inflammatory and coagulation markers was “fascinating.”

“This is the first paper I’ve seen [suggesting] that. I don’t know if we can extrapolate [the findings] to other populations, but if biomarkers are elevated in patients with COVID-19 and diabetes, then it’s something worth looking into, and to be aware of and cautious of. We need to pay attention to this,” he commented.

The study was led by Weina Guo and Desheng Hu at Huazhong University of Science and Technology in Wuhan, China, and published in Diabetes/Metabolism Research and Reviews.

The sample included 174 patients with COVID-19, who were treated consecutively during Feb. 10-29, 2020, at a single center. The researchers first assigned the patients to one of two groups – those with comorbid diabetes and those without. They further excluded all other comorbidities, focusing only on 26 patients with no comorbidities and 24 with only diabetes as a comorbidity, to remove all other comorbidities as possible confounding factors. Patients in the diabetes group were significantly older than those without diabetes (61 vs. 41 years, P < .01). The mortality rate was 16.5% in patients with diabetes and 0% in those without (P = .03).

COVID-19 patients with diabetes alone as a comorbidity had a greater risk for severe pneumonia, as evidenced by a higher mean CT score, compared with those without diabetes and no other comorbidities (P = .04). Patients with diabetes also had higher measures of release of tissue injury–related enzymes and were at higher risk of uncontrolled inflammation and hypercoagulable state. In particular, they had higher levels of interleukin-6 (13.7 vs. 4.1 pg/mL, respectively; P < .01), C-reactive protein (76.4 vs. 7.43 mg/L; P < .01), serum ferritin (764.8 vs. 128.9 ng/mL; P < .01), and D-dimer (1.16 vs. 0.25 mcg/mL; P < .01).

“It’s noteworthy that, for diseases that can induce a cytokine storm, IL-6 is a very good predictor of disease severity and prognosis, and its expression time is longer than other cytokines ([tumor necrosis factor] and IL-1). In addition, a significant rise in serum ferritin indicates the activation of the monocyte-macrophage system, which is a crucial part of inflammatory storm. These results indicate that patients with diabetes are susceptible to form an inflammatory storm, which eventually lead to rapid deterioration of COVID-19,” the authors wrote.

They also cited previous findings suggesting that coronavirus might exacerbate, or even cause, diabetes by seriously damaging islets (Acta Diabetol. 2010;47[3]:193-9). “Since viral infection may cause sharp fluctuation of the blood glucose levels of diabetes patients, which adversely affect the recovery of patients, there is reason to suspect that diabetes combined with SARS-CoV-2 pneumonia may form a vicious circle,” they wrote.

That’s one more reason to carefully monitor diabetes patients, said Dr. Rettinger. “Those patients who are able to make insulin might not be able to do so with the infection, and that may last a while, and they may require insulin. You want to keep a watch on things, and if oral agents are not working well, you want to go to insulin as quickly as you can. Probably diabetics should be way more careful and maybe visit the emergency department at earlier than a nondiabetic would.”

Raghavendra Mirmira, MD, PhD, who conducts translational research on diabetes and insulin production, said that the finding was not a complete surprise to him. “With a lot of diseases, having diabetes as a comorbidity can mean worse outcomes, and that’s certainly true of influenza. It was true for the other COVID-like illnesses, such as SARS and MERS,” Dr. Mirmira, who was not involved in the research, said in an interview.

If the findings hold up in larger numbers of patients and across multiple centers, they have the potential to inform patient management, said Dr. Mirmira, director of the Translational Research Center in the department of medicine at the University of Chicago. That will be especially true as data from long-term follow-up of become available. Elevated values in some biomarkers might dictate a patient be sent straight to the ICU or dictate admission to the hospital rather than being sent home, or it could assist patient selection for some of the new therapies that physicians hope will become available.

“The more information we get [about] total outcome, the more informed we’d be about who would benefit from some of the therapies that are in clinical trials now,” he said. Still, it will be a challenge to prove causation, because patients with diabetes have unique clinical characteristics that could also be the source of the difference.

Dr. Mirmira noted that patients with diabetes only were 20 years older on average than those with no comorbidities. “It’s really hard to know if what you’re looking at for the worse outcomes for people with diabetes is because they were older, and we know that older people tend to do much worse with COVID than younger people.” Ideally, patients would also be matched by age, but there are not enough data to do that yet.

The study was funded by the China National Natural Science Foundation. The authors reported no conflicts of interest. Dr. Rettinger has no relevant financial disclosures. Dr. Mirmira is on scientific advisory boards for Veralox Therapeutics, Sigilon Therapeutics, the Indiana Biosciences Research Institute, and the Juvenile Diabetes Research Foundation.
 

SOURCE: Guo W et al. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.

COVID-19 infection in patients with type 2 diabetes is associated with a greater increase in inflammatory and coagulation markers, compared with COVID-19 patients without diabetes, according to preliminary findings from a retrospective analysis of COVID-19 patients in Wuhan, China.

The results, though preliminary, could help explain why patients with diabetes and COVID-19 are at greater risk for more severe disease and death.

The results also suggest that more severe disease in patients with diabetes may be the result of a cytokine storm, in which the patient’s immune system overreacts to the virus and inflicts collateral damage on its own organs, according to Herbert I. Rettinger, MD, a clinical endocrinologist in Orange County, Calif., and member of the editorial advisory board for Clinical Endocrinology News. “Understanding the mechanism might help us understand the best way to treat,” COVID-19 in patients with diabetes, he said in an interview.

Dr. Rettinger, who was not involved in the research, noted that the study included only 24 patients with diabetes. Nevertheless, the finding of heightened inflammatory and coagulation markers was “fascinating.”

“This is the first paper I’ve seen [suggesting] that. I don’t know if we can extrapolate [the findings] to other populations, but if biomarkers are elevated in patients with COVID-19 and diabetes, then it’s something worth looking into, and to be aware of and cautious of. We need to pay attention to this,” he commented.

The study was led by Weina Guo and Desheng Hu at Huazhong University of Science and Technology in Wuhan, China, and published in Diabetes/Metabolism Research and Reviews.

The sample included 174 patients with COVID-19, who were treated consecutively during Feb. 10-29, 2020, at a single center. The researchers first assigned the patients to one of two groups – those with comorbid diabetes and those without. They further excluded all other comorbidities, focusing only on 26 patients with no comorbidities and 24 with only diabetes as a comorbidity, to remove all other comorbidities as possible confounding factors. Patients in the diabetes group were significantly older than those without diabetes (61 vs. 41 years, P < .01). The mortality rate was 16.5% in patients with diabetes and 0% in those without (P = .03).

COVID-19 patients with diabetes alone as a comorbidity had a greater risk for severe pneumonia, as evidenced by a higher mean CT score, compared with those without diabetes and no other comorbidities (P = .04). Patients with diabetes also had higher measures of release of tissue injury–related enzymes and were at higher risk of uncontrolled inflammation and hypercoagulable state. In particular, they had higher levels of interleukin-6 (13.7 vs. 4.1 pg/mL, respectively; P < .01), C-reactive protein (76.4 vs. 7.43 mg/L; P < .01), serum ferritin (764.8 vs. 128.9 ng/mL; P < .01), and D-dimer (1.16 vs. 0.25 mcg/mL; P < .01).

“It’s noteworthy that, for diseases that can induce a cytokine storm, IL-6 is a very good predictor of disease severity and prognosis, and its expression time is longer than other cytokines ([tumor necrosis factor] and IL-1). In addition, a significant rise in serum ferritin indicates the activation of the monocyte-macrophage system, which is a crucial part of inflammatory storm. These results indicate that patients with diabetes are susceptible to form an inflammatory storm, which eventually lead to rapid deterioration of COVID-19,” the authors wrote.

They also cited previous findings suggesting that coronavirus might exacerbate, or even cause, diabetes by seriously damaging islets (Acta Diabetol. 2010;47[3]:193-9). “Since viral infection may cause sharp fluctuation of the blood glucose levels of diabetes patients, which adversely affect the recovery of patients, there is reason to suspect that diabetes combined with SARS-CoV-2 pneumonia may form a vicious circle,” they wrote.

That’s one more reason to carefully monitor diabetes patients, said Dr. Rettinger. “Those patients who are able to make insulin might not be able to do so with the infection, and that may last a while, and they may require insulin. You want to keep a watch on things, and if oral agents are not working well, you want to go to insulin as quickly as you can. Probably diabetics should be way more careful and maybe visit the emergency department at earlier than a nondiabetic would.”

Raghavendra Mirmira, MD, PhD, who conducts translational research on diabetes and insulin production, said that the finding was not a complete surprise to him. “With a lot of diseases, having diabetes as a comorbidity can mean worse outcomes, and that’s certainly true of influenza. It was true for the other COVID-like illnesses, such as SARS and MERS,” Dr. Mirmira, who was not involved in the research, said in an interview.

If the findings hold up in larger numbers of patients and across multiple centers, they have the potential to inform patient management, said Dr. Mirmira, director of the Translational Research Center in the department of medicine at the University of Chicago. That will be especially true as data from long-term follow-up of become available. Elevated values in some biomarkers might dictate a patient be sent straight to the ICU or dictate admission to the hospital rather than being sent home, or it could assist patient selection for some of the new therapies that physicians hope will become available.

“The more information we get [about] total outcome, the more informed we’d be about who would benefit from some of the therapies that are in clinical trials now,” he said. Still, it will be a challenge to prove causation, because patients with diabetes have unique clinical characteristics that could also be the source of the difference.

Dr. Mirmira noted that patients with diabetes only were 20 years older on average than those with no comorbidities. “It’s really hard to know if what you’re looking at for the worse outcomes for people with diabetes is because they were older, and we know that older people tend to do much worse with COVID than younger people.” Ideally, patients would also be matched by age, but there are not enough data to do that yet.

The study was funded by the China National Natural Science Foundation. The authors reported no conflicts of interest. Dr. Rettinger has no relevant financial disclosures. Dr. Mirmira is on scientific advisory boards for Veralox Therapeutics, Sigilon Therapeutics, the Indiana Biosciences Research Institute, and the Juvenile Diabetes Research Foundation.
 

SOURCE: Guo W et al. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.

COVID-19 infection in patients with type 2 diabetes is associated with a greater increase in inflammatory and coagulation markers, compared with COVID-19 patients without diabetes, according to preliminary findings from a retrospective analysis of COVID-19 patients in Wuhan, China.

The results, though preliminary, could help explain why patients with diabetes and COVID-19 are at greater risk for more severe disease and death.

The results also suggest that more severe disease in patients with diabetes may be the result of a cytokine storm, in which the patient’s immune system overreacts to the virus and inflicts collateral damage on its own organs, according to Herbert I. Rettinger, MD, a clinical endocrinologist in Orange County, Calif., and member of the editorial advisory board for Clinical Endocrinology News. “Understanding the mechanism might help us understand the best way to treat,” COVID-19 in patients with diabetes, he said in an interview.

Dr. Rettinger, who was not involved in the research, noted that the study included only 24 patients with diabetes. Nevertheless, the finding of heightened inflammatory and coagulation markers was “fascinating.”

“This is the first paper I’ve seen [suggesting] that. I don’t know if we can extrapolate [the findings] to other populations, but if biomarkers are elevated in patients with COVID-19 and diabetes, then it’s something worth looking into, and to be aware of and cautious of. We need to pay attention to this,” he commented.

The study was led by Weina Guo and Desheng Hu at Huazhong University of Science and Technology in Wuhan, China, and published in Diabetes/Metabolism Research and Reviews.

The sample included 174 patients with COVID-19, who were treated consecutively during Feb. 10-29, 2020, at a single center. The researchers first assigned the patients to one of two groups – those with comorbid diabetes and those without. They further excluded all other comorbidities, focusing only on 26 patients with no comorbidities and 24 with only diabetes as a comorbidity, to remove all other comorbidities as possible confounding factors. Patients in the diabetes group were significantly older than those without diabetes (61 vs. 41 years, P < .01). The mortality rate was 16.5% in patients with diabetes and 0% in those without (P = .03).

COVID-19 patients with diabetes alone as a comorbidity had a greater risk for severe pneumonia, as evidenced by a higher mean CT score, compared with those without diabetes and no other comorbidities (P = .04). Patients with diabetes also had higher measures of release of tissue injury–related enzymes and were at higher risk of uncontrolled inflammation and hypercoagulable state. In particular, they had higher levels of interleukin-6 (13.7 vs. 4.1 pg/mL, respectively; P < .01), C-reactive protein (76.4 vs. 7.43 mg/L; P < .01), serum ferritin (764.8 vs. 128.9 ng/mL; P < .01), and D-dimer (1.16 vs. 0.25 mcg/mL; P < .01).

“It’s noteworthy that, for diseases that can induce a cytokine storm, IL-6 is a very good predictor of disease severity and prognosis, and its expression time is longer than other cytokines ([tumor necrosis factor] and IL-1). In addition, a significant rise in serum ferritin indicates the activation of the monocyte-macrophage system, which is a crucial part of inflammatory storm. These results indicate that patients with diabetes are susceptible to form an inflammatory storm, which eventually lead to rapid deterioration of COVID-19,” the authors wrote.

They also cited previous findings suggesting that coronavirus might exacerbate, or even cause, diabetes by seriously damaging islets (Acta Diabetol. 2010;47[3]:193-9). “Since viral infection may cause sharp fluctuation of the blood glucose levels of diabetes patients, which adversely affect the recovery of patients, there is reason to suspect that diabetes combined with SARS-CoV-2 pneumonia may form a vicious circle,” they wrote.

That’s one more reason to carefully monitor diabetes patients, said Dr. Rettinger. “Those patients who are able to make insulin might not be able to do so with the infection, and that may last a while, and they may require insulin. You want to keep a watch on things, and if oral agents are not working well, you want to go to insulin as quickly as you can. Probably diabetics should be way more careful and maybe visit the emergency department at earlier than a nondiabetic would.”

Raghavendra Mirmira, MD, PhD, who conducts translational research on diabetes and insulin production, said that the finding was not a complete surprise to him. “With a lot of diseases, having diabetes as a comorbidity can mean worse outcomes, and that’s certainly true of influenza. It was true for the other COVID-like illnesses, such as SARS and MERS,” Dr. Mirmira, who was not involved in the research, said in an interview.

If the findings hold up in larger numbers of patients and across multiple centers, they have the potential to inform patient management, said Dr. Mirmira, director of the Translational Research Center in the department of medicine at the University of Chicago. That will be especially true as data from long-term follow-up of become available. Elevated values in some biomarkers might dictate a patient be sent straight to the ICU or dictate admission to the hospital rather than being sent home, or it could assist patient selection for some of the new therapies that physicians hope will become available.

“The more information we get [about] total outcome, the more informed we’d be about who would benefit from some of the therapies that are in clinical trials now,” he said. Still, it will be a challenge to prove causation, because patients with diabetes have unique clinical characteristics that could also be the source of the difference.

Dr. Mirmira noted that patients with diabetes only were 20 years older on average than those with no comorbidities. “It’s really hard to know if what you’re looking at for the worse outcomes for people with diabetes is because they were older, and we know that older people tend to do much worse with COVID than younger people.” Ideally, patients would also be matched by age, but there are not enough data to do that yet.

The study was funded by the China National Natural Science Foundation. The authors reported no conflicts of interest. Dr. Rettinger has no relevant financial disclosures. Dr. Mirmira is on scientific advisory boards for Veralox Therapeutics, Sigilon Therapeutics, the Indiana Biosciences Research Institute, and the Juvenile Diabetes Research Foundation.
 

SOURCE: Guo W et al. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.

MAUI, HAWAII – Filgotinib, the oral Janus kinase (JAK) inhibitor now under Food and Drug Administration review for the treatment of RA, has a better safety profile than some of the approved oral JAK inhibitors, but that’s unlikely to save it from being saddled with a black-box safety warning label, experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“There’s probably a class label out there,” according to Mark C. Genovese, MD, professor of medicine and clinical chief of the division of immunology and rheumatology at Stanford (Calif.) University.

He cited the example of upadacitinib (Rinvoq), approved last year as the third oral JAK inhibitor for RA. Even though venous thromboembolic (VTE) events weren’t seen with any significantly increased frequency, compared with placebo, in the upadacitinib development program – unlike for the earlier-approved tofacitinib (Xeljanz) and baricitinib (Olumiant) –the FDA nevertheless required that upadacitinib’s product labeling include this black-box warning: “Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.”

“I would fully expect that there’ll be a similar label in the filgotinib package insert saying that VTEs have been seen in other members of the class,” he predicted.

His copanelist Roy Fleischmann, MD, noted that filgotinib displayed a clean long-term safety profile in a pooled analysis of the 24-week results in the 2,088 filgotinib-treated participants in all phase 3 clinical trials for RA. For example, the incidence of herpes zoster in that large treated population was a mere 0.1%.

“Herpes zoster is almost nonexistent across the program,” observed Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

That’s consistent with what he’s heard from Japanese investigators about their experience. They tell him that in their studies the incidence of herpes zoster with filgotinib is five times less than with other JAK inhibitors.

The long-term pooled phase 3 filgotinib safety data also show less than a 0.1% incidence of adjudicated VTE/pulmonary embolism through 24 weeks. That’s a substantially lower rate than with tofacitinib or baricitinib, he noted.

The two rheumatologists, long-time observers of the FDA regulatory scene, stressed that they have no inside information regarding what the agency will do about filgotinib. It seems beyond doubt that the JAK inhibitor will be approved. But an open question of practical importance to clinicians is whether the agency will approve only the 100-mg dose or the 200-mg dose as well. The panelists agreed that having access to both would be advantageous since the clinical trials data indicate the higher dose is more effective and this greater efficacy doesn’t come at a cost of additional safety issues.

“If the 100 mg is sufficient, that’s great, but the reality is if you want to push to low disease activity or remission, the 200 mg seems to work better, particularly in patients who’ve already failed TNF [tumor necrosis factor] inhibitors or other biologics,” Dr. Genovese said. “If you’re not having additional safety concerns and you can get additional efficacy, I love the idea of having flexibility.”

Dr. Fleischmann is skeptical that the regulators will see things that way.

“There is a real risk that the FDA will do what it’s done before and say: ‘Well, the 200 works and the 100 works, so we’re going to approve the lower dose.’ But there doesn’t appear to be a big safety difference between 100 and 200. So I can see why they would approve the two doses, but I think that’d be unusual,” according to the rheumatologist.
 

The RA pipeline

The two speakers also highlighted several agents with novel mechanisms of action moving through the RA developmental pipeline, including olokizumab, otilimab, fenebrutinib, and a promising oral selective interleukin-1 receptor–associated kinase 4 inhibitor (IRAK4).

Olokizumab: This humanized monoclonal antibody targets IL-6. It has a different mechanism of action than the two commercially available IL-6 inhibitors approved for RA, tocilizumab (Actemra) and sarilumab (Kevzara), in that olokizumab uniquely targets the IL-6 ligand.

At the 2019 annual meeting of the American College of Rheumatology, Dr. Genovese presented the positive findings of a double-blind, placebo-controlled, randomized, phase 3 clinical trial of olokizumab in 428 RA patients with an inadequate response to methotrexate. The primary outcome, an ACR 20 response at 12 weeks, occurred in 25.9% of patients on placebo, 63.6% with 64 mg of olokizumab given subcutaneously every 2 weeks, and 70.4% with 64 mg every 4 weeks, with all participants on background methotrexate. An ACR 50 response at week 24 occurred in 7.7%, 42.7%, and 48.6%, respectively, with an acceptable side effect profile.

This was the first phase 3 trial to be presented from a large, ongoing phase 3 olokizumab developmental program for a variety of diseases.

“The results certainly support the idea that a 4-week regimen would probably be quite useful with this medication, although we’ll have to see what happens with the remaining phase 3 trials,” Dr. Genovese said.

Dr. Fleischmann posed a question: Do we really need a third IL-6 inhibitor?

That would make for a crowded field, Dr. Genovese agreed, adding that grabbing a reasonable market share for olokizumab may come down to cost, formulary access, and the convenience factor of once-monthly dosing. Whether the biologic’s unique mechanism of action in blocking the IL-6 ligand makes any practical difference in outcomes is unknown.

IRAK4 inhibitor: PF-06650833 is an oral selective reversible inhibitor of IRAK4, a key signaling kinase for IL-1 and toll-like receptors.

“This should be a really good drug for IL-1-mediated diseases,” according to Dr. Fleischmann.

In a phase 2b, double-blind, randomized, placebo-controlled, 12-week study featuring tofacitinib at 5 mg twice daily as an active comparator, the IRAK4 inhibitor exhibited dose-dependent efficacy for the primary endpoint of improvement from baseline in Simple Disease Activity Index score, compared with placebo. The same was true for the secondary endpoint, change over time in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP). The trial results were also presented at the 2019 ACR annual meeting.

“This is a drug they should probably take forward and see how far it goes in RA,” he said.

Dr. Genovese concurred.

“We’re still trying to figure out how we can put together rational combinations in RA, and this might be something that could be considered as a combination play. In fact, Pfizer has already teed up a study looking at a JAK inhibitor/IRAK4 combination. The question will be whether this is a standalone or has an opportunity to be part of a combination approach,” the rheumatologist said.

Otilimab: This monoclonal antibody is a granulocyte-macrophage colony-stimulating factor inhibitor. In a secondary analysis of the BAROQUE trial, a phase 2b, 50-week study in RA inadequately responsive to methotrexate, otilimab demonstrated an impressive effect in terms of pain reduction. This new analysis, which was first presented at the 2019 ACR annual meeting, showed that, at week 12, a minimum clinically important difference in pain was achieved in 29% of placebo-treated controls, compared with 65%-75% of patients on low to higher doses of otilimab.

“The question is: Is this pain effect unique to this molecule, this pathway, or is it a simple reflection of the treated patient population?” Dr. Genovese commented. “It’s an interesting molecule. It’s being developed in RA, and it might have unique benefits on the pain side.”

A tale of two BTK inhibitors: Bruton tyrosine kinase (BTK) is an intracellular kinase viewed as a promising target in autoimmune disease. Fenebrutinib is an oral, noncovalent, reversible, and highly selective BTK inhibitor that performed well in a phase 2, randomized, double-blind, placebo-controlled clinical trial with adalimumab as an active comparator in 480 patients with an inadequate response to methotrexate in one branch, and in 98 patients with an inadequate response to TNF inhibitor therapy in the other. All subjects were on background methotrexate. (The study results were published April 9 in Arthritis & Rheumatology.)

In the group with a prior inadequate response to TNF inhibitors, the ACR 50 response rate at 12 weeks was 25% in the group on fenebrutinib at 200 mg twice daily, significantly better than the 12% rate in placebo. And there were favorable effects on biomarkers: The reduction in erythrocyte sedimentation rate from baseline was nearly twice as great with fenebrutinib, the drop in CRP was nearly three times greater than with placebo, and there was also a significantly greater decrease over time in DAS28-CRP.

In the methotrexate-inadequate responders, the ACR50 rates were 28% and 35% with the BTK inhibitor at 150 and 200 mg once daily, respectively, compared with 15% in controls.

The safety picture was encouraging, with similarly low adverse event rates across all treatment arms.

In contrast to the fenebrutinib experience, Dr. Genovese was lead investigator in a 250-patient, phase 2 study of another oral BTK inhibitor, poseltinib, which differs from fenebrutinib in that it is an irreversible covalent inhibitor. It was a failed study, with no significant difference between poseltinib and placebo in ACR 20 response at 12 weeks. It’s unclear whether the problem was insufficient dosing or that poseltinib is a failed molecule, perhaps because of its irreversible covalent binding to BTK, he said.
 

Other notable failures

The spleen tyrosine kinase (Syk) inhibitor known as GS-9876 showed no clinical efficacy in a phase 2, double-blind, randomized trial in 83 RA patients with an inadequate response to methotrexate or a biologic DMARD.

“This is like the fourth Syk inhibitor that’s failed. Syk inhibition is not sick, Syk is dead,” Dr. Fleischmann declared.

Cadherin-11 is an inflammatory cytokine expressed on fibroblasts in RA joints. In a phase 2, double-blind, randomized trial in 109 patients with RA inadequately responsive to TNF inhibitors, RG6125, a humanized monoclonal antibody directed against cadherin-11, failed to outperform placebo.

“It should have worked. It didn’t. So the question is whether this pathway is not an appropriate pathway, or the molecule was not quite the right molecule. I have a feeling it was possibly not the right molecule and the pathway may be viable,” according to Dr. Fleischmann.

He reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Genovese also reported financial relationships with more than a dozen pharmaceutical companies.
 

bjancin@mdedge.com

MAUI, HAWAII – Filgotinib, the oral Janus kinase (JAK) inhibitor now under Food and Drug Administration review for the treatment of RA, has a better safety profile than some of the approved oral JAK inhibitors, but that’s unlikely to save it from being saddled with a black-box safety warning label, experts agreed at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

“There’s probably a class label out there,” according to Mark C. Genovese, MD, professor of medicine and clinical chief of the division of immunology and rheumatology at Stanford (Calif.) University.

He cited the example of upadacitinib (Rinvoq), approved last year as the third oral JAK inhibitor for RA. Even though venous thromboembolic (VTE) events weren’t seen with any significantly increased frequency, compared with placebo, in the upadacitinib development program – unlike for the earlier-approved tofacitinib (Xeljanz) and baricitinib (Olumiant) –the FDA nevertheless required that upadacitinib’s product labeling include this black-box warning: “Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.”

“I would fully expect that there’ll be a similar label in the filgotinib package insert saying that VTEs have been seen in other members of the class,” he predicted.

His copanelist Roy Fleischmann, MD, noted that filgotinib displayed a clean long-term safety profile in a pooled analysis of the 24-week results in the 2,088 filgotinib-treated participants in all phase 3 clinical trials for RA. For example, the incidence of herpes zoster in that large treated population was a mere 0.1%.

“Herpes zoster is almost nonexistent across the program,” observed Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.

That’s consistent with what he’s heard from Japanese investigators about their experience. They tell him that in their studies the incidence of herpes zoster with filgotinib is five times less than with other JAK inhibitors.

The long-term pooled phase 3 filgotinib safety data also show less than a 0.1% incidence of adjudicated VTE/pulmonary embolism through 24 weeks. That’s a substantially lower rate than with tofacitinib or baricitinib, he noted.

The two rheumatologists, long-time observers of the FDA regulatory scene, stressed that they have no inside information regarding what the agency will do about filgotinib. It seems beyond doubt that the JAK inhibitor will be approved. But an open question of practical importance to clinicians is whether the agency will approve only the 100-mg dose or the 200-mg dose as well. The panelists agreed that having access to both would be advantageous since the clinical trials data indicate the higher dose is more effective and this greater efficacy doesn’t come at a cost of additional safety issues.

“If the 100 mg is sufficient, that’s great, but the reality is if you want to push to low disease activity or remission, the 200 mg seems to work better, particularly in patients who’ve already failed TNF [tumor necrosis factor] inhibitors or other biologics,” Dr. Genovese said. “If you’re not having additional safety concerns and you can get additional efficacy, I love the idea of having flexibility.”

Dr. Fleischmann is skeptical that the regulators will see things that way.

“There is a real risk that the FDA will do what it’s done before and say: ‘Well, the 200 works and the 100 works, so we’re going to approve the lower dose.’ But there doesn’t appear to be a big safety difference between 100 and 200. So I can see why they would approve the two doses, but I think that’d be unusual,” according to the rheumatologist.
 

The RA pipeline

The two speakers also highlighted several agents with novel mechanisms of action moving through the RA developmental pipeline, including olokizumab, otilimab, fenebrutinib, and a promising oral selective interleukin-1 receptor–associated kinase 4 inhibitor (IRAK4).

Olokizumab: This humanized monoclonal antibody targets IL-6. It has a different mechanism of action than the two commercially available IL-6 inhibitors approved for RA, tocilizumab (Actemra) and sarilumab (Kevzara), in that olokizumab uniquely targets the IL-6 ligand.

At the 2019 annual meeting of the American College of Rheumatology, Dr. Genovese presented the positive findings of a double-blind, placebo-controlled, randomized, phase 3 clinical trial of olokizumab in 428 RA patients with an inadequate response to methotrexate. The primary outcome, an ACR 20 response at 12 weeks, occurred in 25.9% of patients on placebo, 63.6% with 64 mg of olokizumab given subcutaneously every 2 weeks, and 70.4% with 64 mg every 4 weeks, with all participants on background methotrexate. An ACR 50 response at week 24 occurred in 7.7%, 42.7%, and 48.6%, respectively, with an acceptable side effect profile.

This was the first phase 3 trial to be presented from a large, ongoing phase 3 olokizumab developmental program for a variety of diseases.

“The results certainly support the idea that a 4-week regimen would probably be quite useful with this medication, although we’ll have to see what happens with the remaining phase 3 trials,” Dr. Genovese said.

Dr. Fleischmann posed a question: Do we really need a third IL-6 inhibitor?

That would make for a crowded field, Dr. Genovese agreed, adding that grabbing a reasonable market share for olokizumab may come down to cost, formulary access, and the convenience factor of once-monthly dosing. Whether the biologic’s unique mechanism of action in blocking the IL-6 ligand makes any practical difference in outcomes is unknown.

IRAK4 inhibitor: PF-06650833 is an oral selective reversible inhibitor of IRAK4, a key signaling kinase for IL-1 and toll-like receptors.

“This should be a really good drug for IL-1-mediated diseases,” according to Dr. Fleischmann.

In a phase 2b, double-blind, randomized, placebo-controlled, 12-week study featuring tofacitinib at 5 mg twice daily as an active comparator, the IRAK4 inhibitor exhibited dose-dependent efficacy for the primary endpoint of improvement from baseline in Simple Disease Activity Index score, compared with placebo. The same was true for the secondary endpoint, change over time in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP). The trial results were also presented at the 2019 ACR annual meeting.

“This is a drug they should probably take forward and see how far it goes in RA,” he said.

Dr. Genovese concurred.

“We’re still trying to figure out how we can put together rational combinations in RA, and this might be something that could be considered as a combination play. In fact, Pfizer has already teed up a study looking at a JAK inhibitor/IRAK4 combination. The question will be whether this is a standalone or has an opportunity to be part of a combination approach,” the rheumatologist said.

Otilimab: This monoclonal antibody is a granulocyte-macrophage colony-stimulating factor inhibitor. In a secondary analysis of the BAROQUE trial, a phase 2b, 50-week study in RA inadequately responsive to methotrexate, otilimab demonstrated an impressive effect in terms of pain reduction. This new analysis, which was first presented at the 2019 ACR annual meeting, showed that, at week 12, a minimum clinically important difference in pain was achieved in 29% of placebo-treated controls, compared with 65%-75% of patients on low to higher doses of otilimab.

“The question is: Is this pain effect unique to this molecule, this pathway, or is it a simple reflection of the treated patient population?” Dr. Genovese commented. “It’s an interesting molecule. It’s being developed in RA, and it might have unique benefits on the pain side.”

A tale of two BTK inhibitors: Bruton tyrosine kinase (BTK) is an intracellular kinase viewed as a promising target in autoimmune disease. Fenebrutinib is an oral, noncovalent, reversible, and highly selective BTK inhibitor that performed well in a phase 2, randomized, double-blind, placebo-controlled clinical trial with adalimumab as an active comparator in 480 patients with an inadequate response to methotrexate in one branch, and in 98 patients with an inadequate response to TNF inhibitor therapy in the other. All subjects were on background methotrexate. (The study results were published April 9 in Arthritis & Rheumatology.)

In the group with a prior inadequate response to TNF inhibitors, the ACR 50 response rate at 12 weeks was 25% in the group on fenebrutinib at 200 mg twice daily, significantly better than the 12% rate in placebo. And there were favorable effects on biomarkers: The reduction in erythrocyte sedimentation rate from baseline was nearly twice as great with fenebrutinib, the drop in CRP was nearly three times greater than with placebo, and there was also a significantly greater decrease over time in DAS28-CRP.

In the methotrexate-inadequate responders, the ACR50 rates were 28% and 35% with the BTK inhibitor at 150 and 200 mg once daily, respectively, compared with 15% in controls.

The safety picture was encouraging, with similarly low adverse event rates across all treatment arms.

In contrast to the fenebrutinib experience, Dr. Genovese was lead investigator in a 250-patient, phase 2 study of another oral BTK inhibitor, poseltinib, which differs from fenebrutinib in that it is an irreversible covalent inhibitor. It was a failed study, with no significant difference between poseltinib and placebo in ACR 20 response at 12 weeks. It’s unclear whether the problem was insufficient dosing or that poseltinib is a failed molecule, perhaps because of its irreversible covalent binding to BTK, he said.