A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

A new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.

CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.

Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.

But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”

CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.

The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).

Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”

Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”

This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”

Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”

This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.

But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.

Ms. Bulens and Dr. Price reported no relevant financial relationships.

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

Ultrasound and Chest Imaging Section

Advanced critical care echocardiography: A noninvasive tool for hemodynamic assessment in critically ill patients

Hemodynamic assessments in critically ill patients are important to guide accurate management; however, traditional invasive methods of measuring cardiac output have significant limitations, including risks of infection and bleeding. Advanced critical care echocardiography (ACCE) is a feasible alternative, which can be used to provide accurate hemodynamic assessment at the point of care. ACCE can provide a multitude of hemodynamic measurements from cardiac output (CO) to right ventricular systolic pressure (RVSP) and left atrial pressure (LAP). Combinations of left ventricular function parameters, along with estimation of filling pressures, can help distinguish between types of shock. Schmidt and colleagues (Sci Rep. 2022;12[1]:7187) demonstrated that measurement of these indices in the majority of patients helped elucidate the cause for hemodynamic compromise. They found presence of a cardiac index (CI) < 2.5/min.m² was associated with a doubling of ICU mortality as compared with predictions based on severity of illness scores in otherwise hemodynamically stable patients. Hollenberg and colleagues (Am J Cardiol. 2021;153:135-39) demonstrated the feasibility of a simpler stratification using the left ventricular ejection fraction (LVEF) and CI in coronavirus disease 2019 patients with shock, where low CI despite having a preserved LVEF was associated with worse outcomes.

Quick, reliable data are an intensivist’s friend. Utilizing ACCE at the bedside adds another tool in our arsenal to provide real-time hemodynamic data that can be used to manage patients in the ICU. ACCE also allows repeated measurements to determine changes based on therapeutic interventions initiated.

In recognition of the importance of ACCE as a tool for intensivists, the National Board of Echocardiography (NBE) now offers a pathway toward board certification with the Examination of Special Competence in Critical Care Echocardiography (CCEeXAM). CHEST continues to offer cutting-edge courses in ACCE, as well as a board review course for learners interested in sitting for the CCEeXAM.

Amik Sodhi, MD, FCCP
Gul Zaidi, MD, FCCP

Members-at-Large

Ultrasound and Chest Imaging Section

Advanced critical care echocardiography: A noninvasive tool for hemodynamic assessment in critically ill patients

Hemodynamic assessments in critically ill patients are important to guide accurate management; however, traditional invasive methods of measuring cardiac output have significant limitations, including risks of infection and bleeding. Advanced critical care echocardiography (ACCE) is a feasible alternative, which can be used to provide accurate hemodynamic assessment at the point of care. ACCE can provide a multitude of hemodynamic measurements from cardiac output (CO) to right ventricular systolic pressure (RVSP) and left atrial pressure (LAP). Combinations of left ventricular function parameters, along with estimation of filling pressures, can help distinguish between types of shock. Schmidt and colleagues (Sci Rep. 2022;12[1]:7187) demonstrated that measurement of these indices in the majority of patients helped elucidate the cause for hemodynamic compromise. They found presence of a cardiac index (CI) < 2.5/min.m² was associated with a doubling of ICU mortality as compared with predictions based on severity of illness scores in otherwise hemodynamically stable patients. Hollenberg and colleagues (Am J Cardiol. 2021;153:135-39) demonstrated the feasibility of a simpler stratification using the left ventricular ejection fraction (LVEF) and CI in coronavirus disease 2019 patients with shock, where low CI despite having a preserved LVEF was associated with worse outcomes.

Quick, reliable data are an intensivist’s friend. Utilizing ACCE at the bedside adds another tool in our arsenal to provide real-time hemodynamic data that can be used to manage patients in the ICU. ACCE also allows repeated measurements to determine changes based on therapeutic interventions initiated.

In recognition of the importance of ACCE as a tool for intensivists, the National Board of Echocardiography (NBE) now offers a pathway toward board certification with the Examination of Special Competence in Critical Care Echocardiography (CCEeXAM). CHEST continues to offer cutting-edge courses in ACCE, as well as a board review course for learners interested in sitting for the CCEeXAM.

Amik Sodhi, MD, FCCP
Gul Zaidi, MD, FCCP

Members-at-Large

Ultrasound and Chest Imaging Section

Advanced critical care echocardiography: A noninvasive tool for hemodynamic assessment in critically ill patients

Hemodynamic assessments in critically ill patients are important to guide accurate management; however, traditional invasive methods of measuring cardiac output have significant limitations, including risks of infection and bleeding. Advanced critical care echocardiography (ACCE) is a feasible alternative, which can be used to provide accurate hemodynamic assessment at the point of care. ACCE can provide a multitude of hemodynamic measurements from cardiac output (CO) to right ventricular systolic pressure (RVSP) and left atrial pressure (LAP). Combinations of left ventricular function parameters, along with estimation of filling pressures, can help distinguish between types of shock. Schmidt and colleagues (Sci Rep. 2022;12[1]:7187) demonstrated that measurement of these indices in the majority of patients helped elucidate the cause for hemodynamic compromise. They found presence of a cardiac index (CI) < 2.5/min.m² was associated with a doubling of ICU mortality as compared with predictions based on severity of illness scores in otherwise hemodynamically stable patients. Hollenberg and colleagues (Am J Cardiol. 2021;153:135-39) demonstrated the feasibility of a simpler stratification using the left ventricular ejection fraction (LVEF) and CI in coronavirus disease 2019 patients with shock, where low CI despite having a preserved LVEF was associated with worse outcomes.

Quick, reliable data are an intensivist’s friend. Utilizing ACCE at the bedside adds another tool in our arsenal to provide real-time hemodynamic data that can be used to manage patients in the ICU. ACCE also allows repeated measurements to determine changes based on therapeutic interventions initiated.

In recognition of the importance of ACCE as a tool for intensivists, the National Board of Echocardiography (NBE) now offers a pathway toward board certification with the Examination of Special Competence in Critical Care Echocardiography (CCEeXAM). CHEST continues to offer cutting-edge courses in ACCE, as well as a board review course for learners interested in sitting for the CCEeXAM.

Amik Sodhi, MD, FCCP
Gul Zaidi, MD, FCCP

Members-at-Large

Most vaccines don’t come as one-shot deals. A series of boosters is needed to step up immunity to COVID-19, tetanus, and other infectious threats over time.

But what if you could receive just one shot that boosts itself whenever you need a bump in protection?

Researchers at the Massachusetts Institute of Technology (MIT) have developed microparticles that could be used to create self-boosting vaccines that deliver their contents at carefully set time points. In a new study published in the journal Science Advances, the scientists describe how they tune the particles to release the goods at the right time and offer insights on how they can keep the particles stable until then.
 

How self-boosting vaccines could work

The team developed tiny particles that look like coffee cups – except instead of your favorite brew, they’re filled with vaccine.

“You can put the lid on, and then inject it into the body, and once the lid breaks, whatever is in there is released,” says study author Ana Jaklenec, PhD, a research scientist at MIT’s Koch Institute for Integrative Cancer Research.

To make the tiny cups, the researchers use various polymers already used in medical applications, such as dissolvable stitches. Then they fill the cups with vaccine material that is dried and combined with sugars and other stabilizers.

The particles can be made in various shapes and fine-tuned using polymers with different properties. Some polymers last longer in the body than others, so their choice helps determine how long everything will stay stable under the skin after the injection and when the particles will release their cargo. It could be days or months after the injection.

One challenge is that as the particles open, the environment around them becomes more acidic. The team is working on ways to curb that acidity to make the vaccine material more stable.

“We have ongoing research that has produced some really, really exciting results about their stability and [shows] that you’re able to maintain really sensitive vaccines, stable for a good period of time,” says study author Morteza Sarmadi, PhD, a research specialist at the Koch Institute.
 

The potential public health impact

This research, funded by the Bill & Melinda Gates Foundation, started with the developing world in mind.

“The intent was actually helping people in the developing world, because a lot of times, people don’t come back for a second injection,” says study author Robert Langer, ScD, the David H. Koch Institute professor at MIT.

But a one-shot plan could benefit the developed world, too. One reason is that self-boosting vaccines could help those who get one achieve higher antibody responses than they would with just one dose. That could mean more protection for the person and the population, because as people develop stronger immunity, germs may have less of a chance to evolve and spread.

Take the COVID-19 pandemic, for example. Only 67% of Americans are fully vaccinated, and most people eligible for first and second boosters haven’t gotten them. New variants, such as the recent Omicron ones, continue to emerge and infect.

“I think those variants would have had a lot less chance to come about if everybody that had gotten vaccinated the first time got repeat injections, which they didn’t,” says Dr. Langer.

Self-boosting vaccines could also benefit infants, children who fear shots, and older adults who have a hard time getting health care.

Also, because the vaccine material is encapsulated and its release can be staggered, this technology might help people receive multiple vaccines at the same time that must now be given separately.
 

What comes next

The team is testing self-boosting polio and hepatitis vaccines in non-human primates. A small trial in healthy humans might follow within the next few years.

“We think that there’s really high potential for this technology, and we hope it can be developed and get to the human phase very soon,” says Dr. Jaklenec.

In smaller animal models, they are exploring the potential of self-boosting mRNA vaccines. They’re also working with scientists who are studying HIV vaccines.

“There has been some recent progress where very complex regimens seem to be working, but they’re not practical,” says Dr. Jaklenec. “And so, this is where this particular technology could be useful, because you have to prime and boost with different things, and this allows you to do that.”

This system could also extend beyond vaccines and be used to deliver cancer therapies, hormones, and biologics in a shot.

Through new work with researchers at Georgia Tech University, the team will study the potential of giving self-boosting vaccines through 3D-printed microneedles. These vaccines, which would stick on your skin like a bandage, could be self-administered and deployed globally in response to local outbreaks.

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

Most vaccines don’t come as one-shot deals. A series of boosters is needed to step up immunity to COVID-19, tetanus, and other infectious threats over time.

But what if you could receive just one shot that boosts itself whenever you need a bump in protection?

Researchers at the Massachusetts Institute of Technology (MIT) have developed microparticles that could be used to create self-boosting vaccines that deliver their contents at carefully set time points. In a new study published in the journal Science Advances, the scientists describe how they tune the particles to release the goods at the right time and offer insights on how they can keep the particles stable until then.
 

How self-boosting vaccines could work

The team developed tiny particles that look like coffee cups – except instead of your favorite brew, they’re filled with vaccine.

“You can put the lid on, and then inject it into the body, and once the lid breaks, whatever is in there is released,” says study author Ana Jaklenec, PhD, a research scientist at MIT’s Koch Institute for Integrative Cancer Research.

To make the tiny cups, the researchers use various polymers already used in medical applications, such as dissolvable stitches. Then they fill the cups with vaccine material that is dried and combined with sugars and other stabilizers.

The particles can be made in various shapes and fine-tuned using polymers with different properties. Some polymers last longer in the body than others, so their choice helps determine how long everything will stay stable under the skin after the injection and when the particles will release their cargo. It could be days or months after the injection.

One challenge is that as the particles open, the environment around them becomes more acidic. The team is working on ways to curb that acidity to make the vaccine material more stable.

“We have ongoing research that has produced some really, really exciting results about their stability and [shows] that you’re able to maintain really sensitive vaccines, stable for a good period of time,” says study author Morteza Sarmadi, PhD, a research specialist at the Koch Institute.
 

The potential public health impact

This research, funded by the Bill & Melinda Gates Foundation, started with the developing world in mind.

“The intent was actually helping people in the developing world, because a lot of times, people don’t come back for a second injection,” says study author Robert Langer, ScD, the David H. Koch Institute professor at MIT.

But a one-shot plan could benefit the developed world, too. One reason is that self-boosting vaccines could help those who get one achieve higher antibody responses than they would with just one dose. That could mean more protection for the person and the population, because as people develop stronger immunity, germs may have less of a chance to evolve and spread.

Take the COVID-19 pandemic, for example. Only 67% of Americans are fully vaccinated, and most people eligible for first and second boosters haven’t gotten them. New variants, such as the recent Omicron ones, continue to emerge and infect.

“I think those variants would have had a lot less chance to come about if everybody that had gotten vaccinated the first time got repeat injections, which they didn’t,” says Dr. Langer.

Self-boosting vaccines could also benefit infants, children who fear shots, and older adults who have a hard time getting health care.

Also, because the vaccine material is encapsulated and its release can be staggered, this technology might help people receive multiple vaccines at the same time that must now be given separately.
 

What comes next

The team is testing self-boosting polio and hepatitis vaccines in non-human primates. A small trial in healthy humans might follow within the next few years.

“We think that there’s really high potential for this technology, and we hope it can be developed and get to the human phase very soon,” says Dr. Jaklenec.

In smaller animal models, they are exploring the potential of self-boosting mRNA vaccines. They’re also working with scientists who are studying HIV vaccines.

“There has been some recent progress where very complex regimens seem to be working, but they’re not practical,” says Dr. Jaklenec. “And so, this is where this particular technology could be useful, because you have to prime and boost with different things, and this allows you to do that.”

This system could also extend beyond vaccines and be used to deliver cancer therapies, hormones, and biologics in a shot.

Through new work with researchers at Georgia Tech University, the team will study the potential of giving self-boosting vaccines through 3D-printed microneedles. These vaccines, which would stick on your skin like a bandage, could be self-administered and deployed globally in response to local outbreaks.

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

Most vaccines don’t come as one-shot deals. A series of boosters is needed to step up immunity to COVID-19, tetanus, and other infectious threats over time.

But what if you could receive just one shot that boosts itself whenever you need a bump in protection?

Researchers at the Massachusetts Institute of Technology (MIT) have developed microparticles that could be used to create self-boosting vaccines that deliver their contents at carefully set time points. In a new study published in the journal Science Advances, the scientists describe how they tune the particles to release the goods at the right time and offer insights on how they can keep the particles stable until then.
 

How self-boosting vaccines could work

The team developed tiny particles that look like coffee cups – except instead of your favorite brew, they’re filled with vaccine.

“You can put the lid on, and then inject it into the body, and once the lid breaks, whatever is in there is released,” says study author Ana Jaklenec, PhD, a research scientist at MIT’s Koch Institute for Integrative Cancer Research.

To make the tiny cups, the researchers use various polymers already used in medical applications, such as dissolvable stitches. Then they fill the cups with vaccine material that is dried and combined with sugars and other stabilizers.

The particles can be made in various shapes and fine-tuned using polymers with different properties. Some polymers last longer in the body than others, so their choice helps determine how long everything will stay stable under the skin after the injection and when the particles will release their cargo. It could be days or months after the injection.

One challenge is that as the particles open, the environment around them becomes more acidic. The team is working on ways to curb that acidity to make the vaccine material more stable.

“We have ongoing research that has produced some really, really exciting results about their stability and [shows] that you’re able to maintain really sensitive vaccines, stable for a good period of time,” says study author Morteza Sarmadi, PhD, a research specialist at the Koch Institute.
 

The potential public health impact

This research, funded by the Bill & Melinda Gates Foundation, started with the developing world in mind.

“The intent was actually helping people in the developing world, because a lot of times, people don’t come back for a second injection,” says study author Robert Langer, ScD, the David H. Koch Institute professor at MIT.

But a one-shot plan could benefit the developed world, too. One reason is that self-boosting vaccines could help those who get one achieve higher antibody responses than they would with just one dose. That could mean more protection for the person and the population, because as people develop stronger immunity, germs may have less of a chance to evolve and spread.

Take the COVID-19 pandemic, for example. Only 67% of Americans are fully vaccinated, and most people eligible for first and second boosters haven’t gotten them. New variants, such as the recent Omicron ones, continue to emerge and infect.

“I think those variants would have had a lot less chance to come about if everybody that had gotten vaccinated the first time got repeat injections, which they didn’t,” says Dr. Langer.

Self-boosting vaccines could also benefit infants, children who fear shots, and older adults who have a hard time getting health care.

Also, because the vaccine material is encapsulated and its release can be staggered, this technology might help people receive multiple vaccines at the same time that must now be given separately.
 

What comes next

The team is testing self-boosting polio and hepatitis vaccines in non-human primates. A small trial in healthy humans might follow within the next few years.

“We think that there’s really high potential for this technology, and we hope it can be developed and get to the human phase very soon,” says Dr. Jaklenec.

In smaller animal models, they are exploring the potential of self-boosting mRNA vaccines. They’re also working with scientists who are studying HIV vaccines.

“There has been some recent progress where very complex regimens seem to be working, but they’re not practical,” says Dr. Jaklenec. “And so, this is where this particular technology could be useful, because you have to prime and boost with different things, and this allows you to do that.”

This system could also extend beyond vaccines and be used to deliver cancer therapies, hormones, and biologics in a shot.

Through new work with researchers at Georgia Tech University, the team will study the potential of giving self-boosting vaccines through 3D-printed microneedles. These vaccines, which would stick on your skin like a bandage, could be self-administered and deployed globally in response to local outbreaks.

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

Interventional Procedures Section

Mind the gap: Improving adherence to lung cancer screening follow-up

The gap in adherence rates between a disciplined clinical trial and the heterogenous patchwork of U.S. health care is hardly unusual, but as lung cancer remains the number one cancer killer both worldwide and in the United States, one such disparity bears closer scrutiny.

In 2011, the National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality with the implementation of low dose CT scan screening with 95% adherence to CT scan follow-up within 15 months of initial screening imaging (Aberle, et al. N Engl J Med. 2011;365[5]:395-409). Unfortunately, estimates of real-world adherence to lung cancer screening (LCS) follow-up fall to 51% even within an extended 18-month window (Hirsch, et al. Ann Am Thorac Soc. 2019;16[10]:1329-32).

Recent studies compared adherence to LCS follow-up between centralized and decentralized screening programs. Centralized programs used dedicated program coordinators and a tracking system, while decentralized programs relied on primary care providers. Patients enrolled in a centralized program had a two-fold higher likelihood of adherence when compared with those screened in a decentralized program (Sakoda, et al. JAMA Network Open. 2021;4[4]:e218559). A subsequent study demonstrated adherence of 70% vs 41% among patients in centralized vs decentralized programs, respectively (Smith, et al. Chest. 2022;161[3]:818-25).

This gap is even more pronounced in majority-Black populations. Kunitomo and colleagues showed 33% lower odds of adherence to LCS follow-up compared with White patients (Kunitomo, et al. Chest. 2022;161[1]:266-75). Another study in a diverse, majority-Black patient population showed only 31% adherence to LCS follow-up at 1 year (Erkmen, et al. Cancer Causes Control. 2021;32[3]:291-8).

How could we close this gap? Centralized LCS programs show promise of increasing adherence to LCS follow-up. Heightened awareness of and targeted investment to mitigate racial inequities in LCS is imperative.

Jose De Cardenas MD
John Howe, MD

Members-at-Large

Interventional Procedures Section

Mind the gap: Improving adherence to lung cancer screening follow-up

The gap in adherence rates between a disciplined clinical trial and the heterogenous patchwork of U.S. health care is hardly unusual, but as lung cancer remains the number one cancer killer both worldwide and in the United States, one such disparity bears closer scrutiny.

In 2011, the National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality with the implementation of low dose CT scan screening with 95% adherence to CT scan follow-up within 15 months of initial screening imaging (Aberle, et al. N Engl J Med. 2011;365[5]:395-409). Unfortunately, estimates of real-world adherence to lung cancer screening (LCS) follow-up fall to 51% even within an extended 18-month window (Hirsch, et al. Ann Am Thorac Soc. 2019;16[10]:1329-32).

Recent studies compared adherence to LCS follow-up between centralized and decentralized screening programs. Centralized programs used dedicated program coordinators and a tracking system, while decentralized programs relied on primary care providers. Patients enrolled in a centralized program had a two-fold higher likelihood of adherence when compared with those screened in a decentralized program (Sakoda, et al. JAMA Network Open. 2021;4[4]:e218559). A subsequent study demonstrated adherence of 70% vs 41% among patients in centralized vs decentralized programs, respectively (Smith, et al. Chest. 2022;161[3]:818-25).

This gap is even more pronounced in majority-Black populations. Kunitomo and colleagues showed 33% lower odds of adherence to LCS follow-up compared with White patients (Kunitomo, et al. Chest. 2022;161[1]:266-75). Another study in a diverse, majority-Black patient population showed only 31% adherence to LCS follow-up at 1 year (Erkmen, et al. Cancer Causes Control. 2021;32[3]:291-8).

How could we close this gap? Centralized LCS programs show promise of increasing adherence to LCS follow-up. Heightened awareness of and targeted investment to mitigate racial inequities in LCS is imperative.

Jose De Cardenas MD
John Howe, MD

Members-at-Large

Interventional Procedures Section

Mind the gap: Improving adherence to lung cancer screening follow-up

The gap in adherence rates between a disciplined clinical trial and the heterogenous patchwork of U.S. health care is hardly unusual, but as lung cancer remains the number one cancer killer both worldwide and in the United States, one such disparity bears closer scrutiny.

In 2011, the National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality with the implementation of low dose CT scan screening with 95% adherence to CT scan follow-up within 15 months of initial screening imaging (Aberle, et al. N Engl J Med. 2011;365[5]:395-409). Unfortunately, estimates of real-world adherence to lung cancer screening (LCS) follow-up fall to 51% even within an extended 18-month window (Hirsch, et al. Ann Am Thorac Soc. 2019;16[10]:1329-32).

Recent studies compared adherence to LCS follow-up between centralized and decentralized screening programs. Centralized programs used dedicated program coordinators and a tracking system, while decentralized programs relied on primary care providers. Patients enrolled in a centralized program had a two-fold higher likelihood of adherence when compared with those screened in a decentralized program (Sakoda, et al. JAMA Network Open. 2021;4[4]:e218559). A subsequent study demonstrated adherence of 70% vs 41% among patients in centralized vs decentralized programs, respectively (Smith, et al. Chest. 2022;161[3]:818-25).

This gap is even more pronounced in majority-Black populations. Kunitomo and colleagues showed 33% lower odds of adherence to LCS follow-up compared with White patients (Kunitomo, et al. Chest. 2022;161[1]:266-75). Another study in a diverse, majority-Black patient population showed only 31% adherence to LCS follow-up at 1 year (Erkmen, et al. Cancer Causes Control. 2021;32[3]:291-8).

How could we close this gap? Centralized LCS programs show promise of increasing adherence to LCS follow-up. Heightened awareness of and targeted investment to mitigate racial inequities in LCS is imperative.

Jose De Cardenas MD
John Howe, MD

Members-at-Large

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

Cases of early-stage prostate cancer could be missed because official guidelines and health messaging place a misleading emphasis on urinary symptoms, according to experts.

Researchers from the University of Cambridge said there was “no evidence of a causal link between prostate cancer and either prostate size or troublesome male urinary symptoms” and called for early prostate cancer to be rebranded “as primarily an asymptomatic disease” to encourage more men to get tested earlier when the condition is more treatable.

The authors of the ‘Opinion’ article, published in the journal BMC Medicine, argued that persistence by health bodies in flagging prostate cancer as a symptomatic disease – frequently presenting with slow urinary flow, frequency, and nocturia – worked against efforts to reduce mortality rates, which had remained largely unaltered in the UK and many other countries over the past decade and largely driven by late detection.

Public advice by the NHS, for instance, acknowledges that prostate cancer may be symptomless for many years but lists ‘an increased need to pee,’ ‘straining while you pee,’ and ‘a feeling that your bladder has not fully emptied’ as the top three signs that should not be ignored.
 

Messaging gives men ‘a false sense of security’

No wonder, the authors argued, that lower urinary tract symptoms and prostate cancer risk had become “causally associated,” as reflected in a 2003 survey finding that 86% of the public thought that prostate cancer was accompanied by symptoms, while only 1% were aware that it could be asymptomatic.

Lead study author Vincent Gnanapragasam, PhD, professor of urology at the University of Cambridge and an honorary consultant urologist at Addenbrooke’s Hospital, maintained: “We urgently need to recognize that the information currently given to the public risks giving men a false sense of security if they don’t have any urinary symptoms. We need to emphasize that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting out for urinary symptoms may mean missing opportunities to catch the disease when it’s treatable.”

Although prostate enlargement can cause the lower urinary tract problems mentioned in public health messaging, the researchers said this is rarely due to malignant prostate tumors, quoting some research suggesting that “mean prostate volume was lower in men found to have prostate cancer compared to those with benign biopsies.” The Prostate testing for cancer and Treatment (ProtecT) trial in the UK concluded there was “no association or a negative association with more severe symptoms and prostate cancer,” they said.
 

Screening program

The researchers said they were not advocating introducing an immediate screening program, and they acknowledged that updating advice to focus on the often symptomless nature of the disease could lead to an influx of men requesting a PSA test from their GPs. But concerns this could result in overinvestigation and overtreatment “which previously deterred greater promotion of PSA testing in men with no symptoms” had been lessened by today’s “image-based diagnostics and risk-adapted management strategies,” they said.

The authors hoped for an eventual “intelligent tiered screening program” for prostate cancer to be introduced. In the meantime, Dr. Gnanapragasam said, “We’re calling on organizations such as the NHS, as well as patient charities and the media, to review the current public messaging.”

Amy Rylance, head of improving care at Prostate Cancer UK said: “This study reinforces the fact that men shouldn’t wait for symptoms before they act. Early prostate cancer is often symptomless, which is why we urge men to be aware of their risk instead. This is particularly important for men over 50, Black men, and men with a family history of prostate cancer.

“We know that most people assume that they would have symptoms if they had prostate cancer, and that not having straightforward signs to look out for can cause anxiety or confusion. That’s why our risk checker is designed to help men understand their risk factors and what action they can take, regardless of symptoms.”

A version of this article first appeared on Medscape.co.uk.

Cases of early-stage prostate cancer could be missed because official guidelines and health messaging place a misleading emphasis on urinary symptoms, according to experts.

Researchers from the University of Cambridge said there was “no evidence of a causal link between prostate cancer and either prostate size or troublesome male urinary symptoms” and called for early prostate cancer to be rebranded “as primarily an asymptomatic disease” to encourage more men to get tested earlier when the condition is more treatable.

The authors of the ‘Opinion’ article, published in the journal BMC Medicine, argued that persistence by health bodies in flagging prostate cancer as a symptomatic disease – frequently presenting with slow urinary flow, frequency, and nocturia – worked against efforts to reduce mortality rates, which had remained largely unaltered in the UK and many other countries over the past decade and largely driven by late detection.

Public advice by the NHS, for instance, acknowledges that prostate cancer may be symptomless for many years but lists ‘an increased need to pee,’ ‘straining while you pee,’ and ‘a feeling that your bladder has not fully emptied’ as the top three signs that should not be ignored.
 

Messaging gives men ‘a false sense of security’

No wonder, the authors argued, that lower urinary tract symptoms and prostate cancer risk had become “causally associated,” as reflected in a 2003 survey finding that 86% of the public thought that prostate cancer was accompanied by symptoms, while only 1% were aware that it could be asymptomatic.

Lead study author Vincent Gnanapragasam, PhD, professor of urology at the University of Cambridge and an honorary consultant urologist at Addenbrooke’s Hospital, maintained: “We urgently need to recognize that the information currently given to the public risks giving men a false sense of security if they don’t have any urinary symptoms. We need to emphasize that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting out for urinary symptoms may mean missing opportunities to catch the disease when it’s treatable.”

Although prostate enlargement can cause the lower urinary tract problems mentioned in public health messaging, the researchers said this is rarely due to malignant prostate tumors, quoting some research suggesting that “mean prostate volume was lower in men found to have prostate cancer compared to those with benign biopsies.” The Prostate testing for cancer and Treatment (ProtecT) trial in the UK concluded there was “no association or a negative association with more severe symptoms and prostate cancer,” they said.
 

Screening program

The researchers said they were not advocating introducing an immediate screening program, and they acknowledged that updating advice to focus on the often symptomless nature of the disease could lead to an influx of men requesting a PSA test from their GPs. But concerns this could result in overinvestigation and overtreatment “which previously deterred greater promotion of PSA testing in men with no symptoms” had been lessened by today’s “image-based diagnostics and risk-adapted management strategies,” they said.

The authors hoped for an eventual “intelligent tiered screening program” for prostate cancer to be introduced. In the meantime, Dr. Gnanapragasam said, “We’re calling on organizations such as the NHS, as well as patient charities and the media, to review the current public messaging.”

Amy Rylance, head of improving care at Prostate Cancer UK said: “This study reinforces the fact that men shouldn’t wait for symptoms before they act. Early prostate cancer is often symptomless, which is why we urge men to be aware of their risk instead. This is particularly important for men over 50, Black men, and men with a family history of prostate cancer.

“We know that most people assume that they would have symptoms if they had prostate cancer, and that not having straightforward signs to look out for can cause anxiety or confusion. That’s why our risk checker is designed to help men understand their risk factors and what action they can take, regardless of symptoms.”

A version of this article first appeared on Medscape.co.uk.

Cases of early-stage prostate cancer could be missed because official guidelines and health messaging place a misleading emphasis on urinary symptoms, according to experts.

Researchers from the University of Cambridge said there was “no evidence of a causal link between prostate cancer and either prostate size or troublesome male urinary symptoms” and called for early prostate cancer to be rebranded “as primarily an asymptomatic disease” to encourage more men to get tested earlier when the condition is more treatable.

The authors of the ‘Opinion’ article, published in the journal BMC Medicine, argued that persistence by health bodies in flagging prostate cancer as a symptomatic disease – frequently presenting with slow urinary flow, frequency, and nocturia – worked against efforts to reduce mortality rates, which had remained largely unaltered in the UK and many other countries over the past decade and largely driven by late detection.

Public advice by the NHS, for instance, acknowledges that prostate cancer may be symptomless for many years but lists ‘an increased need to pee,’ ‘straining while you pee,’ and ‘a feeling that your bladder has not fully emptied’ as the top three signs that should not be ignored.
 

Messaging gives men ‘a false sense of security’

No wonder, the authors argued, that lower urinary tract symptoms and prostate cancer risk had become “causally associated,” as reflected in a 2003 survey finding that 86% of the public thought that prostate cancer was accompanied by symptoms, while only 1% were aware that it could be asymptomatic.

Lead study author Vincent Gnanapragasam, PhD, professor of urology at the University of Cambridge and an honorary consultant urologist at Addenbrooke’s Hospital, maintained: “We urgently need to recognize that the information currently given to the public risks giving men a false sense of security if they don’t have any urinary symptoms. We need to emphasize that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting out for urinary symptoms may mean missing opportunities to catch the disease when it’s treatable.”

Although prostate enlargement can cause the lower urinary tract problems mentioned in public health messaging, the researchers said this is rarely due to malignant prostate tumors, quoting some research suggesting that “mean prostate volume was lower in men found to have prostate cancer compared to those with benign biopsies.” The Prostate testing for cancer and Treatment (ProtecT) trial in the UK concluded there was “no association or a negative association with more severe symptoms and prostate cancer,” they said.
 

Screening program

The researchers said they were not advocating introducing an immediate screening program, and they acknowledged that updating advice to focus on the often symptomless nature of the disease could lead to an influx of men requesting a PSA test from their GPs. But concerns this could result in overinvestigation and overtreatment “which previously deterred greater promotion of PSA testing in men with no symptoms” had been lessened by today’s “image-based diagnostics and risk-adapted management strategies,” they said.

The authors hoped for an eventual “intelligent tiered screening program” for prostate cancer to be introduced. In the meantime, Dr. Gnanapragasam said, “We’re calling on organizations such as the NHS, as well as patient charities and the media, to review the current public messaging.”

Amy Rylance, head of improving care at Prostate Cancer UK said: “This study reinforces the fact that men shouldn’t wait for symptoms before they act. Early prostate cancer is often symptomless, which is why we urge men to be aware of their risk instead. This is particularly important for men over 50, Black men, and men with a family history of prostate cancer.

“We know that most people assume that they would have symptoms if they had prostate cancer, and that not having straightforward signs to look out for can cause anxiety or confusion. That’s why our risk checker is designed to help men understand their risk factors and what action they can take, regardless of symptoms.”

A version of this article first appeared on Medscape.co.uk.

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

Home-based Mechanical Ventilation and Neuromuscular Disease Section

Navigating the latest device supply chain challenge: Mechanical airway clearance

Airway clearance is integral for patients with respiratory muscle weakness and is divided into cough augmentation (proximal airways) and sputum mobilizing techniques (distal airways). Cough augmentation techniques provide lung volume recruitment on the insufflation phase, in addition to mobilization of secretions with augmentation of the peak expiratory flow rate to >160 L/min on the exhalation phase.

A mechanical insufflation-exsufflation (MI-E) device (T70 Cough Assist - Phillips) is now on indefinite backorder. This creates a dangerous situation for our patients requiring cough augmentation for survival. Alternative options that provide both MI-E and high frequency oscillation include two systems (Synclara Cough System – Hill-rom and the Biwaze Cough System-ABM Respiratory Care).

The Synclara can only be obtained in a direct-to-patient model, contracting with individual respiratory therapists, outside of the standard durable medical equipment model. The final MI-E model option is the VOCSYN multifunctional ventilator (ventilator, cough assist, nebulizer, oxygen concentrator, suction). This multifunction ventilator has had variable acceptance with HCPCS code E0467. If the VOCSYN is chosen, the patient cannot have been issued any component devices or have reached the 36-month cap for oxygen equipment (CR 10854 special payment rule, 42 CFR414.222).

As the supply of devices is exhausted, we will need to shift to evidence-based manual options. Manual cough augmentation can be done effectively with a bag-valve mask, using breath stacking to achieve maximal lung insufflation, optimizing the length tension relationship of elastic recoil on exhalation to increase peak cough flow (PCF).

This can be done alone but is more effective when combined with manually assisted cough (Bach JR. Chest. 1993;104[5]:1553-62). These interventions require training of the caregivers, using resources such as those found at www.canventottawa.ca.

With continued supply chain instability, manual airway clearance techniques should be considered in patients with less advanced cough impairment (PCF 160-270 L/min), to save the remaining devices for those with PCF of <160 L/min.

Jeanette Brown, MD, PhD
Karin Provost, DO, PhD

Members-at-Large

Home-based Mechanical Ventilation and Neuromuscular Disease Section

Navigating the latest device supply chain challenge: Mechanical airway clearance

Airway clearance is integral for patients with respiratory muscle weakness and is divided into cough augmentation (proximal airways) and sputum mobilizing techniques (distal airways). Cough augmentation techniques provide lung volume recruitment on the insufflation phase, in addition to mobilization of secretions with augmentation of the peak expiratory flow rate to >160 L/min on the exhalation phase.

A mechanical insufflation-exsufflation (MI-E) device (T70 Cough Assist - Phillips) is now on indefinite backorder. This creates a dangerous situation for our patients requiring cough augmentation for survival. Alternative options that provide both MI-E and high frequency oscillation include two systems (Synclara Cough System – Hill-rom and the Biwaze Cough System-ABM Respiratory Care).

The Synclara can only be obtained in a direct-to-patient model, contracting with individual respiratory therapists, outside of the standard durable medical equipment model. The final MI-E model option is the VOCSYN multifunctional ventilator (ventilator, cough assist, nebulizer, oxygen concentrator, suction). This multifunction ventilator has had variable acceptance with HCPCS code E0467. If the VOCSYN is chosen, the patient cannot have been issued any component devices or have reached the 36-month cap for oxygen equipment (CR 10854 special payment rule, 42 CFR414.222).

As the supply of devices is exhausted, we will need to shift to evidence-based manual options. Manual cough augmentation can be done effectively with a bag-valve mask, using breath stacking to achieve maximal lung insufflation, optimizing the length tension relationship of elastic recoil on exhalation to increase peak cough flow (PCF).

This can be done alone but is more effective when combined with manually assisted cough (Bach JR. Chest. 1993;104[5]:1553-62). These interventions require training of the caregivers, using resources such as those found at www.canventottawa.ca.

With continued supply chain instability, manual airway clearance techniques should be considered in patients with less advanced cough impairment (PCF 160-270 L/min), to save the remaining devices for those with PCF of <160 L/min.

Jeanette Brown, MD, PhD
Karin Provost, DO, PhD

Members-at-Large

Home-based Mechanical Ventilation and Neuromuscular Disease Section

Navigating the latest device supply chain challenge: Mechanical airway clearance

Airway clearance is integral for patients with respiratory muscle weakness and is divided into cough augmentation (proximal airways) and sputum mobilizing techniques (distal airways). Cough augmentation techniques provide lung volume recruitment on the insufflation phase, in addition to mobilization of secretions with augmentation of the peak expiratory flow rate to >160 L/min on the exhalation phase.

A mechanical insufflation-exsufflation (MI-E) device (T70 Cough Assist - Phillips) is now on indefinite backorder. This creates a dangerous situation for our patients requiring cough augmentation for survival. Alternative options that provide both MI-E and high frequency oscillation include two systems (Synclara Cough System – Hill-rom and the Biwaze Cough System-ABM Respiratory Care).

The Synclara can only be obtained in a direct-to-patient model, contracting with individual respiratory therapists, outside of the standard durable medical equipment model. The final MI-E model option is the VOCSYN multifunctional ventilator (ventilator, cough assist, nebulizer, oxygen concentrator, suction). This multifunction ventilator has had variable acceptance with HCPCS code E0467. If the VOCSYN is chosen, the patient cannot have been issued any component devices or have reached the 36-month cap for oxygen equipment (CR 10854 special payment rule, 42 CFR414.222).

As the supply of devices is exhausted, we will need to shift to evidence-based manual options. Manual cough augmentation can be done effectively with a bag-valve mask, using breath stacking to achieve maximal lung insufflation, optimizing the length tension relationship of elastic recoil on exhalation to increase peak cough flow (PCF).

This can be done alone but is more effective when combined with manually assisted cough (Bach JR. Chest. 1993;104[5]:1553-62). These interventions require training of the caregivers, using resources such as those found at www.canventottawa.ca.

With continued supply chain instability, manual airway clearance techniques should be considered in patients with less advanced cough impairment (PCF 160-270 L/min), to save the remaining devices for those with PCF of <160 L/min.

Jeanette Brown, MD, PhD
Karin Provost, DO, PhD

Members-at-Large

Asthma and COPD Section

Go TEAM! Shared decision-making tool for patient-clinician collaboration in severe asthma

Optimal asthma management requires a patient-clinician collaboration to overcome barriers. Shared decision-making is associated with improved medication adherence in adults (Wilson, et al. Am J Respir Crit Care Med. 2010;181[6]:566-77) and quality of life and asthma control in children (Taylor, et al. J Asthma. 2018;55[6]:675-83). The Global Initiative for Asthma committee recommends a patient-clinician partnership. Activated and engaged patients play a major role in their asthma management (https://ginasthma.org/gina-reports). Shared decision-making discussions should include potential benefits and harms of the therapeutic options, patient’s values and lifestyle preferences, and addressing concerns.

The CHEST Foundation, the Allergy and Asthma Network, and the American College of Allergy, Asthma, and Immunology developed an online shared decision- making tool for severe asthma (https://asthma.chestnet.org/sdm-tool).

This tool utilizes patient’s values, specifics about triggers, asthma control, medication side effects, and lifestyle preferences to identify personalized management options. The tool provides information about recommended therapeutic options in simple terms, including potential benefits, possible side effects, expected treatment frequency and duration, and financial aid information. The treatment options currently explained in this tool include anti-immunoglobulin E, anti-interleukin-5, anti-interleukin-4/13, bronchial thermoplasty, long-acting muscarinic antagonist, macrolides, oral corticosteroids, and standard of care.
 

As a team, the patient and the health care professional can use this tool during office visits to help guide management. Figure 1 shows a suggested workflow to utilize the tool in clinical practice.

Potential barriers include excess time and increased human resources. Barrier mitigation may include reviewing the tool and reconciling the medications before the clinician enters the room. With these interventions, many clinician encounters may be completed in 10 to 15 minutes.

Farrukh Abbas, MBBS
Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Member-at-Large

Asthma and COPD Section

Go TEAM! Shared decision-making tool for patient-clinician collaboration in severe asthma

Optimal asthma management requires a patient-clinician collaboration to overcome barriers. Shared decision-making is associated with improved medication adherence in adults (Wilson, et al. Am J Respir Crit Care Med. 2010;181[6]:566-77) and quality of life and asthma control in children (Taylor, et al. J Asthma. 2018;55[6]:675-83). The Global Initiative for Asthma committee recommends a patient-clinician partnership. Activated and engaged patients play a major role in their asthma management (https://ginasthma.org/gina-reports). Shared decision-making discussions should include potential benefits and harms of the therapeutic options, patient’s values and lifestyle preferences, and addressing concerns.

The CHEST Foundation, the Allergy and Asthma Network, and the American College of Allergy, Asthma, and Immunology developed an online shared decision- making tool for severe asthma (https://asthma.chestnet.org/sdm-tool).

This tool utilizes patient’s values, specifics about triggers, asthma control, medication side effects, and lifestyle preferences to identify personalized management options. The tool provides information about recommended therapeutic options in simple terms, including potential benefits, possible side effects, expected treatment frequency and duration, and financial aid information. The treatment options currently explained in this tool include anti-immunoglobulin E, anti-interleukin-5, anti-interleukin-4/13, bronchial thermoplasty, long-acting muscarinic antagonist, macrolides, oral corticosteroids, and standard of care.
 

As a team, the patient and the health care professional can use this tool during office visits to help guide management. Figure 1 shows a suggested workflow to utilize the tool in clinical practice.

Potential barriers include excess time and increased human resources. Barrier mitigation may include reviewing the tool and reconciling the medications before the clinician enters the room. With these interventions, many clinician encounters may be completed in 10 to 15 minutes.

Farrukh Abbas, MBBS
Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Member-at-Large

Asthma and COPD Section

Go TEAM! Shared decision-making tool for patient-clinician collaboration in severe asthma

Optimal asthma management requires a patient-clinician collaboration to overcome barriers. Shared decision-making is associated with improved medication adherence in adults (Wilson, et al. Am J Respir Crit Care Med. 2010;181[6]:566-77) and quality of life and asthma control in children (Taylor, et al. J Asthma. 2018;55[6]:675-83). The Global Initiative for Asthma committee recommends a patient-clinician partnership. Activated and engaged patients play a major role in their asthma management (https://ginasthma.org/gina-reports). Shared decision-making discussions should include potential benefits and harms of the therapeutic options, patient’s values and lifestyle preferences, and addressing concerns.

The CHEST Foundation, the Allergy and Asthma Network, and the American College of Allergy, Asthma, and Immunology developed an online shared decision- making tool for severe asthma (https://asthma.chestnet.org/sdm-tool).

This tool utilizes patient’s values, specifics about triggers, asthma control, medication side effects, and lifestyle preferences to identify personalized management options. The tool provides information about recommended therapeutic options in simple terms, including potential benefits, possible side effects, expected treatment frequency and duration, and financial aid information. The treatment options currently explained in this tool include anti-immunoglobulin E, anti-interleukin-5, anti-interleukin-4/13, bronchial thermoplasty, long-acting muscarinic antagonist, macrolides, oral corticosteroids, and standard of care.
 

As a team, the patient and the health care professional can use this tool during office visits to help guide management. Figure 1 shows a suggested workflow to utilize the tool in clinical practice.

Potential barriers include excess time and increased human resources. Barrier mitigation may include reviewing the tool and reconciling the medications before the clinician enters the room. With these interventions, many clinician encounters may be completed in 10 to 15 minutes.

Farrukh Abbas, MBBS
Fellow-in-Training

Sandra G. Adams, MD, MS, FCCP
Member-at-Large