Ontario physician Charles Godfrey, MD, who practiced medicine until the age of 102, making him one of the oldest people to ever practice medicine in North America, has died. He was 104 and died at his home in Madoc, Ont., just weeks shy of his 105th birthday.

“He had been quite vigorous up until that point,” his son, Mark Godfrey, told CTV News.

If it wasn’t for the pandemic, his father would have probably continued practicing for a little while longer, he added. “He was the smartest guy in the room, all my life, any room we were in.”

Charles Morris Godfrey was born Sept. 24, 1917, in Philadelphia, according to Wikipedia, but his family moved to Toronto when he was 7 years old. His father, a physiotherapist, encouraged him to study medicine.

Dr. Godfrey served in the Canadian military for 5½ years during World War II and qualified as a physiotherapist while serving.

After the war, he enrolled in the faculty of medicine at the University of Toronto and earned his degree in 1953. He paid for his tuition by working as a janitor and scrapyard worker.

In 1956, he studied neurology at Oxford (England) University on a McLaughlin fellowship and became a fellow of the Royal College of Physicians in 1958. He also earned a bachelor of arts degree in 1962 and his master of arts degree in 1975. He was studying for his PhD in the late 1980s, when he was in his 70s.

Upon his return from England in the late 1950s, Godfrey became director of the department of physical medicine and rehabilitation at Toronto East General Hospital. He subsequently worked at Toronto General Hospital, Sunnybrook Hospital, and the Toronto Rehab Hospital before joining Wellesley Hospital’s rheumatic disease unit, ultimately becoming head of the hospital’s rehabilitation clinic.

Dr. Godfrey was a professor in the department of rehabilitative medicine at the University of Toronto for over 2 decades. He was working 13-hour days teaching and maintaining his own practice well into his 70s. He would spend weekends at his country home in Madoc.

For over 20 years, he and his wife Margaret, a nurse, would spend 6 weeks each year as volunteers traveling to developing countries, such as Afghanistan and Pakistan, on lecture tours on behalf of CARE. Dr. Godfrey chaired CARE/MEDICO from 1983 to 1985 and subsequently served as chairman of CARE’s International Health Advisory Committee. In 1986, he was awarded the organization’s Distinguished Service Award.

In 1989, Dr. Godfrey was invested as a Member of the Order of Canada. His citation reads as follows:

“Deeply committed to humankind and the elimination of human suffering, and although of retirement age, he continues to be involved in an exhausting round of activity. Professor Emeritus of Rehabilitation Medicine at the University of Toronto, an environmentalist who was instrumental in the ‘People or Planes’ campaign opposing construction of the Pickering airport and a director of CARE/MEDICO, each year he takes his heart-felt concern for the welfare of the global community to Third World countries as a visiting volunteer doctor.”

Dr. Godfrey was also a political activist. When he learned about plans to build an international airport near his home in Uxbridge, Ont., he organized People or Planes, a group that successfully opposed the proposed airport. He was elected to the Ontario legislature as the Ontario New Democratic Party’s candidate for Durham West and served for 2 years as the NDP’s environment critic.

In 2020, grandson Frazey Ford posted a clip of his “immortal grandfather” being interviewed by David Suzuki as part of a CBC documentary on aging well.

Dr. Godfrey shared his secret to a long life: “The main thing is to keep interested in life,” he told Mr. Suzuki.

“That’s the secret, of course. If you stick in front of your television, you lose your interest in life. That’ll kill you next week. Certainly, the quality of stuff that’s being peddled on television these days is enough to make you wanna die pretty soon.”

A spokesperson for the University of Toronto’s department of medicine told CTV News that Dr. Godfrey was still working at four medical clinics in Toronto 4 days a week, even at age 102.

“He possessed a remarkable longevity in his practice, supported by his enduring love for medicine and incredible care for his patients,” the university said.

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

Ontario physician Charles Godfrey, MD, who practiced medicine until the age of 102, making him one of the oldest people to ever practice medicine in North America, has died. He was 104 and died at his home in Madoc, Ont., just weeks shy of his 105th birthday.

“He had been quite vigorous up until that point,” his son, Mark Godfrey, told CTV News.

If it wasn’t for the pandemic, his father would have probably continued practicing for a little while longer, he added. “He was the smartest guy in the room, all my life, any room we were in.”

Charles Morris Godfrey was born Sept. 24, 1917, in Philadelphia, according to Wikipedia, but his family moved to Toronto when he was 7 years old. His father, a physiotherapist, encouraged him to study medicine.

Dr. Godfrey served in the Canadian military for 5½ years during World War II and qualified as a physiotherapist while serving.

After the war, he enrolled in the faculty of medicine at the University of Toronto and earned his degree in 1953. He paid for his tuition by working as a janitor and scrapyard worker.

In 1956, he studied neurology at Oxford (England) University on a McLaughlin fellowship and became a fellow of the Royal College of Physicians in 1958. He also earned a bachelor of arts degree in 1962 and his master of arts degree in 1975. He was studying for his PhD in the late 1980s, when he was in his 70s.

Upon his return from England in the late 1950s, Godfrey became director of the department of physical medicine and rehabilitation at Toronto East General Hospital. He subsequently worked at Toronto General Hospital, Sunnybrook Hospital, and the Toronto Rehab Hospital before joining Wellesley Hospital’s rheumatic disease unit, ultimately becoming head of the hospital’s rehabilitation clinic.

Dr. Godfrey was a professor in the department of rehabilitative medicine at the University of Toronto for over 2 decades. He was working 13-hour days teaching and maintaining his own practice well into his 70s. He would spend weekends at his country home in Madoc.

For over 20 years, he and his wife Margaret, a nurse, would spend 6 weeks each year as volunteers traveling to developing countries, such as Afghanistan and Pakistan, on lecture tours on behalf of CARE. Dr. Godfrey chaired CARE/MEDICO from 1983 to 1985 and subsequently served as chairman of CARE’s International Health Advisory Committee. In 1986, he was awarded the organization’s Distinguished Service Award.

In 1989, Dr. Godfrey was invested as a Member of the Order of Canada. His citation reads as follows:

“Deeply committed to humankind and the elimination of human suffering, and although of retirement age, he continues to be involved in an exhausting round of activity. Professor Emeritus of Rehabilitation Medicine at the University of Toronto, an environmentalist who was instrumental in the ‘People or Planes’ campaign opposing construction of the Pickering airport and a director of CARE/MEDICO, each year he takes his heart-felt concern for the welfare of the global community to Third World countries as a visiting volunteer doctor.”

Dr. Godfrey was also a political activist. When he learned about plans to build an international airport near his home in Uxbridge, Ont., he organized People or Planes, a group that successfully opposed the proposed airport. He was elected to the Ontario legislature as the Ontario New Democratic Party’s candidate for Durham West and served for 2 years as the NDP’s environment critic.

In 2020, grandson Frazey Ford posted a clip of his “immortal grandfather” being interviewed by David Suzuki as part of a CBC documentary on aging well.

Dr. Godfrey shared his secret to a long life: “The main thing is to keep interested in life,” he told Mr. Suzuki.

“That’s the secret, of course. If you stick in front of your television, you lose your interest in life. That’ll kill you next week. Certainly, the quality of stuff that’s being peddled on television these days is enough to make you wanna die pretty soon.”

A spokesperson for the University of Toronto’s department of medicine told CTV News that Dr. Godfrey was still working at four medical clinics in Toronto 4 days a week, even at age 102.

“He possessed a remarkable longevity in his practice, supported by his enduring love for medicine and incredible care for his patients,” the university said.

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

Ontario physician Charles Godfrey, MD, who practiced medicine until the age of 102, making him one of the oldest people to ever practice medicine in North America, has died. He was 104 and died at his home in Madoc, Ont., just weeks shy of his 105th birthday.

“He had been quite vigorous up until that point,” his son, Mark Godfrey, told CTV News.

If it wasn’t for the pandemic, his father would have probably continued practicing for a little while longer, he added. “He was the smartest guy in the room, all my life, any room we were in.”

Charles Morris Godfrey was born Sept. 24, 1917, in Philadelphia, according to Wikipedia, but his family moved to Toronto when he was 7 years old. His father, a physiotherapist, encouraged him to study medicine.

Dr. Godfrey served in the Canadian military for 5½ years during World War II and qualified as a physiotherapist while serving.

After the war, he enrolled in the faculty of medicine at the University of Toronto and earned his degree in 1953. He paid for his tuition by working as a janitor and scrapyard worker.

In 1956, he studied neurology at Oxford (England) University on a McLaughlin fellowship and became a fellow of the Royal College of Physicians in 1958. He also earned a bachelor of arts degree in 1962 and his master of arts degree in 1975. He was studying for his PhD in the late 1980s, when he was in his 70s.

Upon his return from England in the late 1950s, Godfrey became director of the department of physical medicine and rehabilitation at Toronto East General Hospital. He subsequently worked at Toronto General Hospital, Sunnybrook Hospital, and the Toronto Rehab Hospital before joining Wellesley Hospital’s rheumatic disease unit, ultimately becoming head of the hospital’s rehabilitation clinic.

Dr. Godfrey was a professor in the department of rehabilitative medicine at the University of Toronto for over 2 decades. He was working 13-hour days teaching and maintaining his own practice well into his 70s. He would spend weekends at his country home in Madoc.

For over 20 years, he and his wife Margaret, a nurse, would spend 6 weeks each year as volunteers traveling to developing countries, such as Afghanistan and Pakistan, on lecture tours on behalf of CARE. Dr. Godfrey chaired CARE/MEDICO from 1983 to 1985 and subsequently served as chairman of CARE’s International Health Advisory Committee. In 1986, he was awarded the organization’s Distinguished Service Award.

In 1989, Dr. Godfrey was invested as a Member of the Order of Canada. His citation reads as follows:

“Deeply committed to humankind and the elimination of human suffering, and although of retirement age, he continues to be involved in an exhausting round of activity. Professor Emeritus of Rehabilitation Medicine at the University of Toronto, an environmentalist who was instrumental in the ‘People or Planes’ campaign opposing construction of the Pickering airport and a director of CARE/MEDICO, each year he takes his heart-felt concern for the welfare of the global community to Third World countries as a visiting volunteer doctor.”

Dr. Godfrey was also a political activist. When he learned about plans to build an international airport near his home in Uxbridge, Ont., he organized People or Planes, a group that successfully opposed the proposed airport. He was elected to the Ontario legislature as the Ontario New Democratic Party’s candidate for Durham West and served for 2 years as the NDP’s environment critic.

In 2020, grandson Frazey Ford posted a clip of his “immortal grandfather” being interviewed by David Suzuki as part of a CBC documentary on aging well.

Dr. Godfrey shared his secret to a long life: “The main thing is to keep interested in life,” he told Mr. Suzuki.

“That’s the secret, of course. If you stick in front of your television, you lose your interest in life. That’ll kill you next week. Certainly, the quality of stuff that’s being peddled on television these days is enough to make you wanna die pretty soon.”

A spokesperson for the University of Toronto’s department of medicine told CTV News that Dr. Godfrey was still working at four medical clinics in Toronto 4 days a week, even at age 102.

“He possessed a remarkable longevity in his practice, supported by his enduring love for medicine and incredible care for his patients,” the university said.

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

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Interstitial Lung Disease Section

Diagnosis of idiopathic pulmonary fibrosis: Is tissue still an issue?

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing disorder of unclear etiology. Per ATS/ERS/JRS/ALAT guidelines, diagnosis of IPF requires exclusion of known causes of interstitial lung disease (ILD) and either the presence of a usual interstitial pneumonia (UIP) or probable UIP pattern on HRCT scan or specific combinations of HRCT scan and histopathologic patterns. Surgical lung biopsy (SLB) is the gold standard for histopathologic diagnosis.

The recent update (Raghu, et al. Am J Respir Crit Care Med. 2022;205[9]:1084-92) made a conditional recommendation for transbronchial lung cryobiopsy (TBLC) as an acceptable alternative to SLB in patients with undetermined ILD. Systematic analysis revealed a diagnostic yield of 79% (85% when ≥ 3 sites were sampled) by TBLC compared with 90% on SLB. With consideration of this diagnostic yield vs the risk of pneumothorax, severe bleeding, and procedural mortality, TBLC is an attractive tool compared with SLB. Overall, the utility of TBLC remains limited to experienced centers due to dependence on proceduralist and pathologist skills for optimal success and more data are awaited.

No recommendation was made for or against the use of genomic classifiers (GC) for the diagnosis of UIP in patients with undetermined ILD undergoing transbronchial biopsy. Although, meta-analysis revealed a specificity of 92%, this may be driven by patient enrichment with a high probability for UIP population. GC has the potential to reduce SLB-associated risks and provide diagnostic information for multidisciplinary discussion in certain scenarios. However, limitations arise from the inability to distinguish specific ILD subtype associated with the UIP pattern; further improvement in sensitivity and understanding of downstream consequences of false-negative results is necessary.

Kevin Dsouza, MD
Fellow-in-Training

Interstitial Lung Disease Section

Diagnosis of idiopathic pulmonary fibrosis: Is tissue still an issue?

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing disorder of unclear etiology. Per ATS/ERS/JRS/ALAT guidelines, diagnosis of IPF requires exclusion of known causes of interstitial lung disease (ILD) and either the presence of a usual interstitial pneumonia (UIP) or probable UIP pattern on HRCT scan or specific combinations of HRCT scan and histopathologic patterns. Surgical lung biopsy (SLB) is the gold standard for histopathologic diagnosis.

The recent update (Raghu, et al. Am J Respir Crit Care Med. 2022;205[9]:1084-92) made a conditional recommendation for transbronchial lung cryobiopsy (TBLC) as an acceptable alternative to SLB in patients with undetermined ILD. Systematic analysis revealed a diagnostic yield of 79% (85% when ≥ 3 sites were sampled) by TBLC compared with 90% on SLB. With consideration of this diagnostic yield vs the risk of pneumothorax, severe bleeding, and procedural mortality, TBLC is an attractive tool compared with SLB. Overall, the utility of TBLC remains limited to experienced centers due to dependence on proceduralist and pathologist skills for optimal success and more data are awaited.

No recommendation was made for or against the use of genomic classifiers (GC) for the diagnosis of UIP in patients with undetermined ILD undergoing transbronchial biopsy. Although, meta-analysis revealed a specificity of 92%, this may be driven by patient enrichment with a high probability for UIP population. GC has the potential to reduce SLB-associated risks and provide diagnostic information for multidisciplinary discussion in certain scenarios. However, limitations arise from the inability to distinguish specific ILD subtype associated with the UIP pattern; further improvement in sensitivity and understanding of downstream consequences of false-negative results is necessary.

Kevin Dsouza, MD
Fellow-in-Training

Interstitial Lung Disease Section

Diagnosis of idiopathic pulmonary fibrosis: Is tissue still an issue?

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing disorder of unclear etiology. Per ATS/ERS/JRS/ALAT guidelines, diagnosis of IPF requires exclusion of known causes of interstitial lung disease (ILD) and either the presence of a usual interstitial pneumonia (UIP) or probable UIP pattern on HRCT scan or specific combinations of HRCT scan and histopathologic patterns. Surgical lung biopsy (SLB) is the gold standard for histopathologic diagnosis.

The recent update (Raghu, et al. Am J Respir Crit Care Med. 2022;205[9]:1084-92) made a conditional recommendation for transbronchial lung cryobiopsy (TBLC) as an acceptable alternative to SLB in patients with undetermined ILD. Systematic analysis revealed a diagnostic yield of 79% (85% when ≥ 3 sites were sampled) by TBLC compared with 90% on SLB. With consideration of this diagnostic yield vs the risk of pneumothorax, severe bleeding, and procedural mortality, TBLC is an attractive tool compared with SLB. Overall, the utility of TBLC remains limited to experienced centers due to dependence on proceduralist and pathologist skills for optimal success and more data are awaited.

No recommendation was made for or against the use of genomic classifiers (GC) for the diagnosis of UIP in patients with undetermined ILD undergoing transbronchial biopsy. Although, meta-analysis revealed a specificity of 92%, this may be driven by patient enrichment with a high probability for UIP population. GC has the potential to reduce SLB-associated risks and provide diagnostic information for multidisciplinary discussion in certain scenarios. However, limitations arise from the inability to distinguish specific ILD subtype associated with the UIP pattern; further improvement in sensitivity and understanding of downstream consequences of false-negative results is necessary.

Kevin Dsouza, MD
Fellow-in-Training

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ultrasound and Chest Imaging Section

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

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

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

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

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

Members-at-Large

Ultrasound and Chest Imaging Section

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

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

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

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

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

Members-at-Large

Ultrasound and Chest Imaging Section

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

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

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

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

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

Members-at-Large

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

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

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

How self-boosting vaccines could work

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

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

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

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

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

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

The potential public health impact

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

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

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

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

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

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

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

What comes next

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

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

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

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

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

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

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

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

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

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

How self-boosting vaccines could work

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

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

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

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

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

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

The potential public health impact

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

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

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

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

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

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

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

What comes next

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

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

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

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

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

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

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

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

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

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

How self-boosting vaccines could work

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

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

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

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

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

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

The potential public health impact

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

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

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

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

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

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

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

What comes next

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

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

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

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

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

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

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

Interventional Procedures Section

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

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

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

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

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

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

Jose De Cardenas MD
John Howe, MD

Members-at-Large

Interventional Procedures Section

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

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

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

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

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

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

Jose De Cardenas MD
John Howe, MD

Members-at-Large

Interventional Procedures Section

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

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

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

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

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

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

Jose De Cardenas MD
John Howe, MD

Members-at-Large

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

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

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

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

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

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

Symptoms that persist

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

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

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

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

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

Closer to a clearer definition

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

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

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

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

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

Effect of hospitalization, vaccination unclear

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Symptoms that persist

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

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

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

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

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

Closer to a clearer definition

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

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

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

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

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

Effect of hospitalization, vaccination unclear

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Symptoms that persist

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

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

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

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

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

Closer to a clearer definition

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

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

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

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

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

Effect of hospitalization, vaccination unclear

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Messaging gives men ‘a false sense of security’

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

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

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

Screening program

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

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

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

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

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

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

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

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

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

Messaging gives men ‘a false sense of security’

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

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

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

Screening program

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

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

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

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

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

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

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

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

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

Messaging gives men ‘a false sense of security’

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

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

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

Screening program

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

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

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

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

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

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

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

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

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

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

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

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

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

Improvements in CLASI-A scores

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

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

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

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

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

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

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

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

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

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

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

Phase 3 trials

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Improvements in CLASI-A scores

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

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

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

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

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

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

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

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

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

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

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

Phase 3 trials

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Improvements in CLASI-A scores

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

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

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

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

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

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

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

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

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

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

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

Phase 3 trials

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

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

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

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

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

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

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