Dermatology News

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

[email protected]

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

[email protected]

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

[email protected]

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.

A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”

The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

During the past decade, the use of photodynamic therapy (PDT) for actinic keratoses (AKs) and other skin lesions has evolved into far more than a single treatment procedure.

Merete Haedersdal, MD, PhD,

“We have conventional PDT, daylight PDT; we can combine with a range of topicals, and we can combine a range of different physical treatment procedures in order to provide better and individualized treatment regimens for our patients,” Merete Haedersdal, MD, PhD, DMSc, professor of dermatology at the University of Copenhagen, said during a course on laser and aesthetic skin therapy.

In Europe, PDT consists of a three-step procedure: curettage of AKs, application of photosensitizer on the skin (typically methyl aminolevulinate, versus aminolevulinic acid, used more often in the United States), and illumination with red light (versus blue light, used more often in the United States), which causes a photochemical reaction.

“It’s a photochemical-reaction concept with which we can achieve up to 90% cure rates of AKs at 3 months,” Dr. Haedersdal said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

PDT is also used in Europe for select patients with Bowen’s disease (yielding a 90% cure rate at 3 months, 70% at 2 years); superficial basal cell carcinoma (yielding a 90% cure rate at 3 months, 75% at 5 years), and nodular BCC (yielding a 90% cure rate at 3 months, 75% at 5 years.

“With conventional PDT, whether it’s blue light, red light, MAL, or ALA, we have beautiful cosmesis, but we also have a challenge, which is pain,” she said. This is behind the motivation to look at other ways to provide PDT.

Daylight PDT, which was pioneered by Dr. Haedersdal’s mentor, Hans Christian Wulf, MD, DMSc, PharmD, professor of dermatology at the University of Copenhagen, provides 80%-90% clearance of thin AKs, lower clearance of thick AKs – and is a nearly pain-free procedure because of continuous photoactivation of protoporphyrin IX, with a Visual Analog Scale in the range of 1-3. “Globally, thousands of patients have been treated [with daylight PDT], which is backed up in the literature with more than 150 publications,” she said.

According to Dr. Haedersdal, MAL cream with daylight activation for treatment of AK was approved in Colombia and Mexico in 2013; in Australia, Brazil, and Costa Rica in 2014; and in Chile, Europe, and New Zealand in 2015. “I do hope that one day you will have daylight PDT approved in the United States,” she said.

The suggested protocol for daylight PDT starts by applying a sunscreen with an organic filter. After about 15 minutes, the lesion or lesions are prepared, and MAL is applied with no occlusion. Patients should start their exposure to daylight within 30 minutes of application, remaining outdoors for 2 hours of continuous exposure, either at a dedicated space located on the ground of the hospital or clinic or at their home. After 2 hours, patients wipe off the remaining cream and are advised to stay indoors for the rest of the day.

“Ideal candidates are those who have large skin areas that can be easily exposed to sunlight,” such as the scalp and lower legs, said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston. “If patients are treated in areas covered by clothing, it can be greasy and sticky with the cream. In these cases, you can cover the area with Tegaderm, which allows for 99% light transmission. Daylight can shine through and the Tegaderm can be removed after the procedure.”

On rainy days between April 1 and October 1 in Copenhagen, she said, daylight PDT is provided in a greenhouse in the hospital garden, with a heater and blankets for patients when the temperature falls below 10° C.

The amount of light required for a treatment effect is 5,000-10,000 lux, and the number of lux on a sunny day in Denmark is about 100,000, she said. “That means that all year round in countries south of latitude 45 degrees N, patients can be treated with daylight PDT.”

To intensify the treatment efficacy of conventional PDT and daylight PDT, especially in those with severely photodamaged skin, combining treatment with a physical pretreatment technique such as curettage, ablative fractional laser, microdermabrasion, microneedling, and nonablative fractional laser is another strategy. A small randomized controlled trial found that ablative fractional laser treatment extended notable relative effectiveness, compared with other physical enhancement techniques.

Dr. Haedersdal and colleagues published a study that compared pretreatment with ablative fractional laser and microdermabrasion pads before daylight PDT for AKs in field-cancerized skin. They found that with a single treatment, combination therapy with ablative fractional laser before daylight PDT led to significantly greater efficacious AK clearance and skin rejuvenation, compared with treatment with microdermabrasion.

“We don’t know why this is, but we believe it may be due to the fact that with the laser, we have a photothermal response, which in combination with the photochemical response from the photodynamic therapy induces a synergistic effect,” she said.

A range of topical treatments can also be given in combination with PDT. In a meta-analysis of 10 randomized controlled trials, German researchers evaluated the efficacy of PDT combined with imiquimod cream, 5-fluorouracil cream, tazarotene gel, and calcipotriol ointment. They concluded that the combination of PDT with another topical drug intervention improves AK clearance rates, compared with monotherapy.

More recently, the same authors summarized the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK in a review article, which Dr. Haedersdal said provides a nice overview of this topic.

Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.

[email protected]

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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