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Epcore NHL-1 Update: Treatment Effective Before CAR T
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.
This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference.
With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.
In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.
Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.
In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.
Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.
At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.
The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%.
Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.
“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.
Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
The Multipronged Problem of Candida auris
The Multipronged Problem of Candida auris
Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.
Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.
In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.
C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.
As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.
Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”
Expediting Diagnoses
Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.
C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.
C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.
Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.
Overcoming Treatment-Resistant Strains
A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.
New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.
Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet.
Infection Prevention and Antimicrobial Stewardship
Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles.
To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.
The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.
Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:
- Overnight international hospitalization
- Recent stay in a long-term acute care facility
- Recent stay in a ventilator skilled nursing facility.
“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”
If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained.
Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.
“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.
Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.
A version of this article appeared on Medscape.com.
Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.
Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.
In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.
C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.
As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.
Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”
Expediting Diagnoses
Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.
C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.
C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.
Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.
Overcoming Treatment-Resistant Strains
A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.
New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.
Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet.
Infection Prevention and Antimicrobial Stewardship
Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles.
To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.
The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.
Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:
- Overnight international hospitalization
- Recent stay in a long-term acute care facility
- Recent stay in a ventilator skilled nursing facility.
“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”
If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained.
Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.
“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.
Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.
A version of this article appeared on Medscape.com.
Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.
Since its discovery in 2009, C auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.
In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors wrote. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.
C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.
As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.
Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”
Expediting Diagnoses
Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.
C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.
C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.
Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.
Overcoming Treatment-Resistant Strains
A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.
New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.
Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thompson, who noted results published in The Lancet.
Infection Prevention and Antimicrobial Stewardship
Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Michigan, have increased measures to tackle the issue from different angles.
To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.
The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.
Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as:
- Overnight international hospitalization
- Recent stay in a long-term acute care facility
- Recent stay in a ventilator skilled nursing facility.
“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”
If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained.
Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.
“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.
Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.
A version of this article appeared on Medscape.com.
The Multipronged Problem of Candida auris
The Multipronged Problem of Candida auris
Could Diet and Gut Bacteria Be Fueling Early CRC?
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
H5N1 Avian Influenza Spreads Across North America
It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.
either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.
The Virus Has Flown to Hawaii
According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected.
Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.
Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.
The Red Alert Lights Up in Canada
The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.
An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.
How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.
Under Special Surveillance for 20 Years
The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.
Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.
Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.
More Vulnerable Than Ever
If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.
The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.
The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.
If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.
In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.
This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.
either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.
The Virus Has Flown to Hawaii
According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected.
Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.
Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.
The Red Alert Lights Up in Canada
The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.
An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.
How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.
Under Special Surveillance for 20 Years
The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.
Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.
Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.
More Vulnerable Than Ever
If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.
The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.
The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.
If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.
In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.
This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
It’s been a while since I’ve discussed the H5N1 avian influenza clade 2.3.4.4b and its rapid spread in North America. I hope the facts prove me wrong, but many experts have been warning for some time that ideal conditions are forming for this virus, which for now only causes zoonoses, to pose a pandemic threat.
either because they work in other medical fields or think that the experience of the COVID-19 pandemic was a worst-case scenario that is unlikely to be repeated in the short term.
The Virus Has Flown to Hawaii
According to data from the Centers for Disease Control and Prevention in Atlanta, Georgia, the infection has now affected more than 500 cattle herds in 15 states. There are about 30 outbreaks reported in poultry, equally distributed between backyard and farm-raised birds, primarily located in California. Here alone, over 3 million birds have been affected.
Wild birds are believed to have transported the highly pathogenic virus via migration routes across the Pacific, introducing it to Hawaii for the first time. Just days after wastewater analysis detected the presence of H5N1 on the island of Oahu, home to the capital Honolulu, the first outbreak was promptly reported, killing at least a dozen ducks and geese in a backyard coop. Some of these birds had been taken in early November to the Mililani Pet Fair, a sort of domestic animal festival. Local authorities recommended that anyone who attended the fair, touched a duck or goose at the event, and developed symptoms including fever, cough, sore throat, and conjunctivitis, should isolate and seek medical advice.
Meanwhile, more than 50 farmers, animal handlers, or workers involved in the slaughter of cattle or poultry across seven states have been confirmed infected, presumably contracted at their workplace. The latest case, diagnosed recently in Oregon, presented with severe conjunctivitis and mild respiratory symptoms. More than half of these patients have been identified in recent weeks in California, where active surveillance measures have been implemented. However, there is strong suspicion that the actual number of people infected with mild symptoms in the rest of the country is much, much higher.
The Red Alert Lights Up in Canada
The level of concern was raised further with news of the first severe — indeed very severe — case of H5N1 avian influenza originating from the western edge of Canada. A teenager (gender not disclosed), previously healthy and without risk factors, was hospitalized with severe respiratory failure in the intensive care unit at British Columbia Children’s Hospital in Vancouver. The source of the infection is unknown, similar to only one other case in Missouri involving an adult already hospitalized for other reasons, which was identified by chance through influenza surveillance programs. We also know that the Canadian adolescent does not live on a farm and had no known contact with potentially infected animals. The only suspicions focus on the family dog, euthanized owing to unspecified health problems in the early days of the epidemiologic investigation. Although the dog tested negative for avian influenza, a necropsy will be conducted to rule out its involvement in the transmission chain.
An initial characterization of the virus has linked it to genotype D1.1, which is circulating among wild birds and poultry farms in Canada’s westernmost province, rather than the strain typical of dairy cows in the United States. The publication of the complete viral sequence over the past weekend has, for the first time, highlighted mutations that could enhance the virus’s ability to infect human cells.
How do we know this? From the highly contested “gain-of-function” studies, which artificially modify viruses to understand which genomic points require the most surveillance — those mutations that can make the infectious agent more virulent or more transmissible between people.
Under Special Surveillance for 20 Years
The influenza A (H5N1) avian virus is not new or previously unknown, like SARS-CoV-2, and this could (in theory) give us a slight advantage. We have known about it for decades, and it began infecting humans about 20 years ago, causing pneumonia with respiratory failure. It proved lethal in about half of the cases, but only in people who had close contact with infected poultry, primarily in Southeast Asia.
Hundreds of other human cases occurred worldwide, but always in low-income countries with poor hygiene conditions and where families lived in close contact with animals. This contributed to a false sense of security in Europe and North America, where the threat has been consistently underestimated. Despite an estimated fatality rate of around 50%, the media often labeled scientists’ warnings and health authorities’ efforts to remain prepared as false alarms, tainted by suspicions of catering to the interests of pharmaceutical companies.
Some people may recall the scandal involving Tamiflu, the Roche antiviral oseltamivir, that governments stockpiled when there were fears that the avian virus might acquire the ability to spread among humans. It was dubbed “a false antidote for a false pandemic,” referring to the potential avian pandemic and the 2009 H1N1 influenza pandemic, improperly called “swine flu,” and which turned out to be less severe than expected. There was talk of €2.64 billion being “wasted” to “please” the manufacturer. Although the Cochrane Collaboration made legitimate demands for rigor and transparency in conducting and publishing clinical trials, much of the public, and the journalists who wrote the stories, cared little about these technical aspects. The prevailing message was that stockpiling drugs (or vaccines) for a disease we don’t even know will occur is a waste of taxpayers’ money rather than a prudent preventive measure.
More Vulnerable Than Ever
If we were to ascribe strategic thinking to the virus, which it is not capable of, we might argue that it chose the ideal moment to conquer the world. It began circulating in the new clade in 2020, when experts and authorities were focused on the coronavirus. It spread from birds to marine mammals and finally to cattle, exploiting the public’s post-pandemic fatigue, as people no longer wanted to hear about infectious diseases and containment measures. It ultimately rode the wave of political polarization that irrationally equates prevention with supposed cowardice on the left, and recklessness with courageous freedom on the right.
The coincidence between the future appointments announced by the incoming Trump administration and the virus’s accelerated spread deserves attention from decision-makers and health professionals worldwide. The COVID-19 pandemic experience should have taught us that ignoring a threat doesn’t make it go away, if not in our health, then at least in our wallet. The economic repercussions of a virus circulating among animals crucial to our food chain and national economies should concern everyone, well before the threat crosses the ocean, because only then can we defend ourselves.
The proposed Secretary of Health and Human Services, Robert F. Kennedy, is a proponent of the supposed benefits of raw milk, which could serve as a potent vector for the virus. He is ideologically opposed to vaccinations. It’s hard to imagine he would utilize the H5N1 vaccine stockpiles held by the US government for a campaign starting at least with farmers, as was done prophylactically in Finland with products jointly procured by 15 European countries — a group the Italian government decided not to join.
If Kennedy indeed becomes responsible for US public health, it’s reasonable to fear that, in the name of freedom, he will try to delay as much as possible — even if necessary — the obligation to undergo testing and wear masks, not to mention more restrictive infection containment measures. It’s also unlikely he would support and promote the development of new mRNA products already under study, which would become indispensable if the disease begins to spread more easily among people, as well as animals. In such a case, traditional influenza vaccine cultivation methods using chicken eggs would prove too slow and quantitatively insufficient, especially if the virus continues to circulate among poultry.
In short, let’s keep our fingers crossed, but recognize that crossing our fingers might not be enough.
This story was translated from Univadis Italy using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Childhood Atopic Dermatitis Doesn’t Delay Puberty
TOPLINE:
METHODOLOGY:
- Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
- The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
- The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).
TAKEAWAY:
- Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
- Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.
IN PRACTICE:
“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.
SOURCE:
The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International.
LIMITATIONS:
Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.
DISCLOSURES:
The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
- The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
- The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).
TAKEAWAY:
- Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
- Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.
IN PRACTICE:
“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.
SOURCE:
The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International.
LIMITATIONS:
Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.
DISCLOSURES:
The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators conducted a nationwide cohort study among 15,534 children in Denmark whose pubertal development was assessed every 6 months with a web-based questionnaire starting at the age of 11 years.
- The children were classified into three groups: No atopic dermatitis; self-reported doctor-diagnosed atopic dermatitis (maternal report of a doctor diagnosis at 6 months, 18 months, and/or 7 years of age); hospital-diagnosed atopic dermatitis (registry data showing it as the primary reason for hospital contact up to the age of 8 years), representing mainly severe cases.
- The main outcome was the age difference averaged across a range of pubertal milestones (attainment of Tanner stages; development of axillary hair, acne, and voice break; and occurrence of first ejaculation and menarche).
TAKEAWAY:
- Overall, 21.5% of the children had self-reported doctor-diagnosed atopic dermatitis and 0.7% had hospital-diagnosed atopic dermatitis.
- Relative to girls without atopic dermatitis, girls with self-reported doctor-diagnosed atopic dermatitis reached the milestones at the same age, with a mean difference of 0.0 months, and girls with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- Relative to boys without atopic dermatitis, boys with self-reported doctor-diagnosed atopic dermatitis reached the milestones a mean of 0.1 month later and boys with hospital-diagnosed atopic dermatitis reached them a mean of 0.3 months earlier.
- A more stringent definition of atopic dermatitis — persistent or recurrent atopic dermatitis at 7 years of age (assumed more likely to affect sleep and disrupt the skin barrier near the start of puberty) — was also not associated with delayed pubertal development.
IN PRACTICE:
“Previous studies on atopic dermatitis and puberty are limited, some suggest a link between atopic dermatitis and delayed puberty, akin to other chronic inflammatory diseases in childhood,” the authors wrote. “The results of the present study are reassuring for young patients with atopic dermatitis approaching puberty and reproductive health in adult life,” they concluded.
SOURCE:
The study was led by Camilla Lomholt Kjersgaard, MD, Aarhus University, Aarhus, Denmark, and was published online in JAAD International.
LIMITATIONS:
Limitations included a lack of information on treatment, the use of analyses that did not address missing data, and a possible misclassification of self-reported pubertal development.
DISCLOSURES:
The study was funded by the Danish Council for Independent Research; Aarhus University; and Fonden af Fam. Kjærsgaard, Sunds; and was cofunded by the European Union. The authors reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Measurement-Based Treatment to Target Approaches
Clinical Scenario
Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?
Metrics Can Guide Next Steps
This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.
Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data.
Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points.
An Alternative Clinical Scenario
Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:
Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time.
You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target.
Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.”
For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:
- Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
- AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care
Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
Clinical Scenario
Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?
Metrics Can Guide Next Steps
This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.
Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data.
Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points.
An Alternative Clinical Scenario
Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:
Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time.
You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target.
Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.”
For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:
- Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
- AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care
Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
Clinical Scenario
Lilly is a 15-year-old girl in her sophomore year of high school. Over the course of a month after a romantic and then a friend-group breakup, her parents have been concerned about her increasing tearfulness every day and retreat from activities to avoid social interactions with others that she once enjoyed so much. She has been missing more and more school, saying that she can’t bear to go, and staying in bed during the days, even on weekends. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment in 2 weeks with you and then again in another 2 weeks. Her parents and she tell you, “I thought she would be better by now.” You feel stuck with how to proceed in the visit. You have correctly identified the problem as depression, started the recommended evidence-based treatments, but the parents and Lilly are looking to you for something more or different. There are not many or other local resources. When and how do you all determine what “better” looks and feels like? Where do you go from here?
Metrics Can Guide Next Steps
This clinical scenario is not uncommon. As a psychiatrist consultant in primary care, I often encounter the following comment and question: “Someone isn’t feeling better. I have them taking an SSRI and doing psychotherapy. What is the next thing to do?” In discussions with supervisees and in training residents, I often say that you will know that your consultations have made a real impact on providers’ practices when these questions shift from “what’s the next medication or treatment” to a more robust baseline and follow-up inventory of symptoms via common and available metrics (PHQ9A, PSC-17 or 30, SCARED) shared with you at the start, the middle, and at other times of treatment. Such metrics can more meaningfully guide your collaborative clinical discussions and decisions.
Tracking baseline metrics and follow-up with treatment interventions is a transformative approach to clinical care. But, in primary care, it’s common that the question around mental health care may not receive the same robust screening and tracking of symptoms which have the power to more thoughtfully guide decision-making, even though this is common in other forms of patient care which have more routine use of more objective data.
Measurement-based treatment to target approaches are well-studied, but not often or always implemented. They involve providing a baseline metric (PHQ9A, Pediatric Symptom Checklist 17 or 30, GAD7, or SCARED), and tracking that metric for response over time using specific scores for decision points.
An Alternative Clinical Scenario
Consider the following alternative scenario for the above patient using a measurement-based treatment to target approach:
Lilly is a 15-year-old girl in her sophomore year of high school with symptoms concerning for depression. A PHQ9A is administered in your appointment, and she scores 20 out of 30, exceeding the threshold score for 11 for depression. You start her on an SSRI and recommend psychotherapy in the form of CBT offered through your office. She returns to the appointment with you in 2 weeks and then again in another 2 weeks. You obtain a PHQ9A at each appointment, and track the change with her and her parents over time.
You share with her and the family that it is common that there will be fluctuations in measurements, and you know that a score change on the PHQ9A greater than 7 is considered a clinically significant, reliable change. So, a PHQ9 score reduction from 20 to 13 would be meaningful progress. While seeking a score within the normal and non-clinical range, the progress can be tracked in a way that allows a more robust monitoring of treatment response. If the scores do not improve, you can see that and act accordingly. This way of using metrics shifts the conversation from “how are you feeling now and today” to tracking symptoms more broadly and tracking those individual symptoms over time, some of which may improve and some which may be trickier to target.
Such a way of tracking common mental health symptoms with a focus on having data at baseline and throughout treatment allows a provider to change or adapt interventions, and to not chase something that can feel ephemeral, such as “feeling happy or looking better.”
For additional information on the measurement-based treatment to target approach, there are resources that share in more depth the research informing this approach, and other and broader real ways to integrate these practices into your own visits:
- Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
- AACAP Clinical Update: Collaborative Mental Health Care for Children and Adolescents in Primary Care
Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
On the Murder of UnitedHealthcare’s CEO
On December 4, UnitedHealthcare CEO Brian Thompson was assassinated in New York City outside of a hotel. As of the time of this writing, the shooter is still at large.
I suppose I could write about how this shows that Americans are fed up with the way modern commercial healthcare companies operate. Who gets care and who doesn’t.
I could write about how industry trends of “Delay, Deny, Defend” lead to the suffering of millions of people who need healthcare that they thought they were paying for.
I could write about the callousness of the way people online are celebrating the cold-blooded murder of a married man with two children.
I might write about how insurance companies intentionally, and routinely, drag out (or deny) reimbursements for physicians (including small solo practice ones, like myself) who are legitimately caring for their patients.
I suppose I could write something about how gun violence is so pervasive in our society that it scarcely merits a second glance at the news story. If the headline just said, “Unknown Assailant Kills Man Outside Hotel,” would you have even read beyond that?
I could write about how the lack of regulations, and accelerating attempts to scrap them, can lead to insider trading.
I could write about how having insurance companies and medical facilities more beholden to shareholders than to patients is a serious conflict of interest.
I could try to make points about how the widespread availability of firearms (in this case one with a built-in silencer) in America means that anyone with a vendetta, or serious mental illness, or just a short temper, can get one — and use it.
I could talk about how “greed is good” in healthcare settings rewards a few and hurts many — no matter how much the PR spinners try to make it sound like it’s a great win-win situation all-around.
I could argue that the jubilant “good riddance” and “eat the rich” responses of many — both medical and nonmedical people — to the killing shows that, as a society, we’re losing the qualities that make us human.
I could also argue that putting financial gain for executive bonuses and stockholder dividends ahead of the health and well-being of others shows that, as a society, we’re losing the qualities that make us human.
I could make a point that , provided the target is someone they have a difference of opinion with. Which is, honestly, pretty damn scary.
I could talk about how policies of arbitrarily changing the rules about anesthesia coverage, or letting a computer decide how long a hospital stay should be, or to deny rehabilitation care, are unethical, unjust, and just plain wrong.
I could write about a lot of things based on what happened outside that New York Hilton Midtown in early December.
But as I stare at my screen, I’m well aware that no matter what I write it won’t change any opinions, solve anything, or even lead to people trying to find a solution.
Because that’s just the world we live in.
Block has a solo neurology practice in Scottsdale, Arizona.
On December 4, UnitedHealthcare CEO Brian Thompson was assassinated in New York City outside of a hotel. As of the time of this writing, the shooter is still at large.
I suppose I could write about how this shows that Americans are fed up with the way modern commercial healthcare companies operate. Who gets care and who doesn’t.
I could write about how industry trends of “Delay, Deny, Defend” lead to the suffering of millions of people who need healthcare that they thought they were paying for.
I could write about the callousness of the way people online are celebrating the cold-blooded murder of a married man with two children.
I might write about how insurance companies intentionally, and routinely, drag out (or deny) reimbursements for physicians (including small solo practice ones, like myself) who are legitimately caring for their patients.
I suppose I could write something about how gun violence is so pervasive in our society that it scarcely merits a second glance at the news story. If the headline just said, “Unknown Assailant Kills Man Outside Hotel,” would you have even read beyond that?
I could write about how the lack of regulations, and accelerating attempts to scrap them, can lead to insider trading.
I could write about how having insurance companies and medical facilities more beholden to shareholders than to patients is a serious conflict of interest.
I could try to make points about how the widespread availability of firearms (in this case one with a built-in silencer) in America means that anyone with a vendetta, or serious mental illness, or just a short temper, can get one — and use it.
I could talk about how “greed is good” in healthcare settings rewards a few and hurts many — no matter how much the PR spinners try to make it sound like it’s a great win-win situation all-around.
I could argue that the jubilant “good riddance” and “eat the rich” responses of many — both medical and nonmedical people — to the killing shows that, as a society, we’re losing the qualities that make us human.
I could also argue that putting financial gain for executive bonuses and stockholder dividends ahead of the health and well-being of others shows that, as a society, we’re losing the qualities that make us human.
I could make a point that , provided the target is someone they have a difference of opinion with. Which is, honestly, pretty damn scary.
I could talk about how policies of arbitrarily changing the rules about anesthesia coverage, or letting a computer decide how long a hospital stay should be, or to deny rehabilitation care, are unethical, unjust, and just plain wrong.
I could write about a lot of things based on what happened outside that New York Hilton Midtown in early December.
But as I stare at my screen, I’m well aware that no matter what I write it won’t change any opinions, solve anything, or even lead to people trying to find a solution.
Because that’s just the world we live in.
Block has a solo neurology practice in Scottsdale, Arizona.
On December 4, UnitedHealthcare CEO Brian Thompson was assassinated in New York City outside of a hotel. As of the time of this writing, the shooter is still at large.
I suppose I could write about how this shows that Americans are fed up with the way modern commercial healthcare companies operate. Who gets care and who doesn’t.
I could write about how industry trends of “Delay, Deny, Defend” lead to the suffering of millions of people who need healthcare that they thought they were paying for.
I could write about the callousness of the way people online are celebrating the cold-blooded murder of a married man with two children.
I might write about how insurance companies intentionally, and routinely, drag out (or deny) reimbursements for physicians (including small solo practice ones, like myself) who are legitimately caring for their patients.
I suppose I could write something about how gun violence is so pervasive in our society that it scarcely merits a second glance at the news story. If the headline just said, “Unknown Assailant Kills Man Outside Hotel,” would you have even read beyond that?
I could write about how the lack of regulations, and accelerating attempts to scrap them, can lead to insider trading.
I could write about how having insurance companies and medical facilities more beholden to shareholders than to patients is a serious conflict of interest.
I could try to make points about how the widespread availability of firearms (in this case one with a built-in silencer) in America means that anyone with a vendetta, or serious mental illness, or just a short temper, can get one — and use it.
I could talk about how “greed is good” in healthcare settings rewards a few and hurts many — no matter how much the PR spinners try to make it sound like it’s a great win-win situation all-around.
I could argue that the jubilant “good riddance” and “eat the rich” responses of many — both medical and nonmedical people — to the killing shows that, as a society, we’re losing the qualities that make us human.
I could also argue that putting financial gain for executive bonuses and stockholder dividends ahead of the health and well-being of others shows that, as a society, we’re losing the qualities that make us human.
I could make a point that , provided the target is someone they have a difference of opinion with. Which is, honestly, pretty damn scary.
I could talk about how policies of arbitrarily changing the rules about anesthesia coverage, or letting a computer decide how long a hospital stay should be, or to deny rehabilitation care, are unethical, unjust, and just plain wrong.
I could write about a lot of things based on what happened outside that New York Hilton Midtown in early December.
But as I stare at my screen, I’m well aware that no matter what I write it won’t change any opinions, solve anything, or even lead to people trying to find a solution.
Because that’s just the world we live in.
Block has a solo neurology practice in Scottsdale, Arizona.
Rheumatology Match: Less than Half of Pediatric Positions Filled, Worsening Existing Trend
Over half of pediatric rheumatology fellowship positions went unfilled in 2024, according to the National Resident Matching Program (NRMP). Comparatively, nearly all adult rheumatology positions were filled.
Across all 39 subspecialties in internal medicine and pediatrics, there was an 86% fill rate. In pediatric subspecialties, the fill rate was 78%. There were more than 10,200 applicants in this year’s medicine and pediatric specialties match — a 9% increase from 2023 — and 81% matched to a position.
The NRMP reported that adult rheumatology filled 129 (97.7%) of 132 programs, with 284 (99%) out of 287 positions filled. In 2024, there were five new programs and 11 more fellowship positions available compared with the previous year.
In pediatric rheumatology, 16 (44%) of 36 programs were filled, with 27 (49%) of 55 positions filled. This is a notable decrease from 2023, where pediatric rheumatology filled 21 of 38 programs (55%) and 32 (62%) of 52 positions.
This year, 27 of 30 applicants preferring pediatric rheumatology matched to a program, while in 2023 all 32 applicants that preferred pediatric rheumatology matched.
“It’s a little disappointing that our overall number of applicants have not gone up,” Jay Mehta, MD, the program director of the Children’s Hospital of Philadelphia’s pediatric rheumatology fellowship said in an interview with Medscape Medical News. “It’s an especially exciting time in pediatric rheumatology, with really fantastic breakthroughs in terms of treatments and diagnostics. Unfortunately, that excitement hasn’t necessarily translated into more interest in our field.”
Mehta noted that the number of applicants to pediatric rheumatology fellowships have remained relatively consistent. Since 2019, the number of applicants has ranged from 28 to 33.
“Given the low number of overall positions/programs it is hard to read too much into year-to-year differences,” added Kristen Hayward, MD, a pediatric rheumatologist at Seattle Children’s in Washington. “While this total number of applicants per year is steady, this number is insufficient to build an adequate workforce for our current needs, much less for the future.”
This year, matched applicants to pediatric rheumatology included 13 MD graduates, eight DO graduates, five foreign applicants, and one US citizen international medical graduate.
In adult rheumatology, matched applicants included 108 MD graduates, 97 foreign applicants, 41 DO graduates, and 38 US citizen international medical graduates. A total of 365 applicants preferred the specialty, and 76% matched to rheumatology. Seven applicants matched to another specialty, and the remaining 79 did not match to any program.
Rheumatology was one of several specialties offering at least 150 positions with a fill rate of over 98%. The other specialties included allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, endocrinology, gastroenterology, and hematology and oncology.
While some pediatric subspecialties like critical care medicine and cardiology had fill rates over 90%, many “cognitive subspecialties” beyond pediatric rheumatology also struggled to fill spots, Hayward noted. Only 37% of pediatric nephrology positions and 48% of pediatric infectious disease positions were filled this year, in addition to a decline in filled pediatric-residency positions overall, she added.
Mehta had no relevant disclosures. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer.
A version of this article first appeared on Medscape.com.
Over half of pediatric rheumatology fellowship positions went unfilled in 2024, according to the National Resident Matching Program (NRMP). Comparatively, nearly all adult rheumatology positions were filled.
Across all 39 subspecialties in internal medicine and pediatrics, there was an 86% fill rate. In pediatric subspecialties, the fill rate was 78%. There were more than 10,200 applicants in this year’s medicine and pediatric specialties match — a 9% increase from 2023 — and 81% matched to a position.
The NRMP reported that adult rheumatology filled 129 (97.7%) of 132 programs, with 284 (99%) out of 287 positions filled. In 2024, there were five new programs and 11 more fellowship positions available compared with the previous year.
In pediatric rheumatology, 16 (44%) of 36 programs were filled, with 27 (49%) of 55 positions filled. This is a notable decrease from 2023, where pediatric rheumatology filled 21 of 38 programs (55%) and 32 (62%) of 52 positions.
This year, 27 of 30 applicants preferring pediatric rheumatology matched to a program, while in 2023 all 32 applicants that preferred pediatric rheumatology matched.
“It’s a little disappointing that our overall number of applicants have not gone up,” Jay Mehta, MD, the program director of the Children’s Hospital of Philadelphia’s pediatric rheumatology fellowship said in an interview with Medscape Medical News. “It’s an especially exciting time in pediatric rheumatology, with really fantastic breakthroughs in terms of treatments and diagnostics. Unfortunately, that excitement hasn’t necessarily translated into more interest in our field.”
Mehta noted that the number of applicants to pediatric rheumatology fellowships have remained relatively consistent. Since 2019, the number of applicants has ranged from 28 to 33.
“Given the low number of overall positions/programs it is hard to read too much into year-to-year differences,” added Kristen Hayward, MD, a pediatric rheumatologist at Seattle Children’s in Washington. “While this total number of applicants per year is steady, this number is insufficient to build an adequate workforce for our current needs, much less for the future.”
This year, matched applicants to pediatric rheumatology included 13 MD graduates, eight DO graduates, five foreign applicants, and one US citizen international medical graduate.
In adult rheumatology, matched applicants included 108 MD graduates, 97 foreign applicants, 41 DO graduates, and 38 US citizen international medical graduates. A total of 365 applicants preferred the specialty, and 76% matched to rheumatology. Seven applicants matched to another specialty, and the remaining 79 did not match to any program.
Rheumatology was one of several specialties offering at least 150 positions with a fill rate of over 98%. The other specialties included allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, endocrinology, gastroenterology, and hematology and oncology.
While some pediatric subspecialties like critical care medicine and cardiology had fill rates over 90%, many “cognitive subspecialties” beyond pediatric rheumatology also struggled to fill spots, Hayward noted. Only 37% of pediatric nephrology positions and 48% of pediatric infectious disease positions were filled this year, in addition to a decline in filled pediatric-residency positions overall, she added.
Mehta had no relevant disclosures. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer.
A version of this article first appeared on Medscape.com.
Over half of pediatric rheumatology fellowship positions went unfilled in 2024, according to the National Resident Matching Program (NRMP). Comparatively, nearly all adult rheumatology positions were filled.
Across all 39 subspecialties in internal medicine and pediatrics, there was an 86% fill rate. In pediatric subspecialties, the fill rate was 78%. There were more than 10,200 applicants in this year’s medicine and pediatric specialties match — a 9% increase from 2023 — and 81% matched to a position.
The NRMP reported that adult rheumatology filled 129 (97.7%) of 132 programs, with 284 (99%) out of 287 positions filled. In 2024, there were five new programs and 11 more fellowship positions available compared with the previous year.
In pediatric rheumatology, 16 (44%) of 36 programs were filled, with 27 (49%) of 55 positions filled. This is a notable decrease from 2023, where pediatric rheumatology filled 21 of 38 programs (55%) and 32 (62%) of 52 positions.
This year, 27 of 30 applicants preferring pediatric rheumatology matched to a program, while in 2023 all 32 applicants that preferred pediatric rheumatology matched.
“It’s a little disappointing that our overall number of applicants have not gone up,” Jay Mehta, MD, the program director of the Children’s Hospital of Philadelphia’s pediatric rheumatology fellowship said in an interview with Medscape Medical News. “It’s an especially exciting time in pediatric rheumatology, with really fantastic breakthroughs in terms of treatments and diagnostics. Unfortunately, that excitement hasn’t necessarily translated into more interest in our field.”
Mehta noted that the number of applicants to pediatric rheumatology fellowships have remained relatively consistent. Since 2019, the number of applicants has ranged from 28 to 33.
“Given the low number of overall positions/programs it is hard to read too much into year-to-year differences,” added Kristen Hayward, MD, a pediatric rheumatologist at Seattle Children’s in Washington. “While this total number of applicants per year is steady, this number is insufficient to build an adequate workforce for our current needs, much less for the future.”
This year, matched applicants to pediatric rheumatology included 13 MD graduates, eight DO graduates, five foreign applicants, and one US citizen international medical graduate.
In adult rheumatology, matched applicants included 108 MD graduates, 97 foreign applicants, 41 DO graduates, and 38 US citizen international medical graduates. A total of 365 applicants preferred the specialty, and 76% matched to rheumatology. Seven applicants matched to another specialty, and the remaining 79 did not match to any program.
Rheumatology was one of several specialties offering at least 150 positions with a fill rate of over 98%. The other specialties included allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, endocrinology, gastroenterology, and hematology and oncology.
While some pediatric subspecialties like critical care medicine and cardiology had fill rates over 90%, many “cognitive subspecialties” beyond pediatric rheumatology also struggled to fill spots, Hayward noted. Only 37% of pediatric nephrology positions and 48% of pediatric infectious disease positions were filled this year, in addition to a decline in filled pediatric-residency positions overall, she added.
Mehta had no relevant disclosures. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer.
A version of this article first appeared on Medscape.com.
Project’s Improvement in JIA Outcome Disparities Sets Stage for Further Interventions
WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.
“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”
Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.
“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.”
It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.
“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.
Targeting Factors That Clinicians Can Potentially Influence
In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.
These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.
The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.
The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.
The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.
As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.
Providing access to at-risk patients included several components:
- Creating a population management team
- Defining a target population to engage with for earlier follow-up
- Using a monthly batch outreach to defined patients
- Having a coordinator or social worker reach out to those who don’t make appointments
- Using a new JIA/high disease activity video follow-up program.
Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.
Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.
One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.
Results of the Quality Improvement Project
As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.
They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.
From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.
In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.
One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.
Abel and Harry had no disclosures. No external funding was noted.
A version of this article appeared on Medscape.com.
WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.
“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”
Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.
“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.”
It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.
“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.
Targeting Factors That Clinicians Can Potentially Influence
In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.
These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.
The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.
The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.
The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.
As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.
Providing access to at-risk patients included several components:
- Creating a population management team
- Defining a target population to engage with for earlier follow-up
- Using a monthly batch outreach to defined patients
- Having a coordinator or social worker reach out to those who don’t make appointments
- Using a new JIA/high disease activity video follow-up program.
Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.
Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.
One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.
Results of the Quality Improvement Project
As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.
They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.
From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.
In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.
One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.
Abel and Harry had no disclosures. No external funding was noted.
A version of this article appeared on Medscape.com.
WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.
“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”
Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.
“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.”
It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.
“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.
Targeting Factors That Clinicians Can Potentially Influence
In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.
These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.
The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.
The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.
The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.
As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.
Providing access to at-risk patients included several components:
- Creating a population management team
- Defining a target population to engage with for earlier follow-up
- Using a monthly batch outreach to defined patients
- Having a coordinator or social worker reach out to those who don’t make appointments
- Using a new JIA/high disease activity video follow-up program.
Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.
Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.
One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.
Results of the Quality Improvement Project
As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.
They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.
From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.
In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.
One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.
Abel and Harry had no disclosures. No external funding was noted.
A version of this article appeared on Medscape.com.
FROM ACR 2024
Could Biomarkers Help to Detect Lung Disease Earlier in Systemic JIA?
WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.
Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.
“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.
Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.
Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.
“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”
Study Results
The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.
Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.
The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).
There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).
Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).
Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).
Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).
In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).
While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.
Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:
- MMP-7 (P = .001)
- IFN gamma (P = .008)
- CCL11 (P < .0001)
- CCL17 (P = .002)
- CCL15 (P < .0001)
- MCP-1 (P = .0003)
- MCP-3 (P = .02)
- CCL25 (P < .0001)
- CD25 (P < .0001)
- GDF-15 (P < .0001)
- TRAIL (P < .0001)
- IL-23 (P = .002)
They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.
The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.
The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.
A version of this article appeared on Medscape.com.
WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.
Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.
“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.
Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.
Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.
“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”
Study Results
The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.
Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.
The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).
There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).
Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).
Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).
Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).
In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).
While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.
Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:
- MMP-7 (P = .001)
- IFN gamma (P = .008)
- CCL11 (P < .0001)
- CCL17 (P = .002)
- CCL15 (P < .0001)
- MCP-1 (P = .0003)
- MCP-3 (P = .02)
- CCL25 (P < .0001)
- CD25 (P < .0001)
- GDF-15 (P < .0001)
- TRAIL (P < .0001)
- IL-23 (P = .002)
They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.
The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.
The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.
A version of this article appeared on Medscape.com.
WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.
Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.
“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.
Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.
Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.
“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”
Study Results
The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.
Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.
The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).
There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).
Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).
Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).
Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).
In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).
While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.
Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:
- MMP-7 (P = .001)
- IFN gamma (P = .008)
- CCL11 (P < .0001)
- CCL17 (P = .002)
- CCL15 (P < .0001)
- MCP-1 (P = .0003)
- MCP-3 (P = .02)
- CCL25 (P < .0001)
- CD25 (P < .0001)
- GDF-15 (P < .0001)
- TRAIL (P < .0001)
- IL-23 (P = .002)
They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.
The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.
The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.
A version of this article appeared on Medscape.com.
FROM ACR 2024