SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

WASHINGTON – Black children had 2.5 greater odds than White children of dying from sepsis in the hospital, despite no significantly different rates of clinical interventions, according to research presented at the annual meeting of the American Academy of Pediatrics.

The only other difference between Black and White pediatric patients was the length of hospital stay and the length of time in the ICU among those who died. In both cases, Black children who died spent more time in the hospital and in the ICU, reported Michael H. Stroud, MD, a pediatric critical care physician at the University of Arkansas for Medical Sciences in Little Rock, and his colleagues.

“Further investigations are needed to identify biases, conscious and unconscious, potential socioeconomic factors, and genetic predispositions leading to racial disparities in outcomes of children with pediatric sepsis, severe sepsis, and septic shock,” Dr Stroud and his colleagues said.

Nathan T. Chomilo, MD, adjunct assistant professor of pediatrics at the University of Minnesota, Minneapolis, who was not involved in the study but reviewed it, said the research “builds upon existing evidence that our health care system has work to do to meet its goal of treating patients equitably and provide everyone the opportunity for health.” He found the racial disparity in death particularly striking in 2023. “In the U.S., with all our wealth, knowledge, and resources, very few children should die from this, let alone there be such a stark gap,” Dr. Chomilo wrote.
 

Racial disparities persist

Dr. Stroud noted that many institutions currently use “automated, real-time, algorithm-based detection of sepsis, severe sepsis, and septic shock incorporated into the electronic medical record,” which leads to earlier recognition and resuscitation and overall better outcomes. Yet racial disparities in sepsis mortality rates persist, and he and his colleagues wanted to explore whether they remained even with these EMR-incorporated systems.

The researchers analyzed data from all patients at Arkansas Children’s Hospital who had sepsis, severe sepsis, or septic shock between January 2018 and April 2022. The hospital uses a best practice advisory (BPA) in the EMR whose activation leads to a bedside huddle and clinical interventions. For this study, the researchers defined a sepsis episode as either a BPA activation or an EMR diagnosis of sepsis, severe sepsis, or septic shock.

Among the 3,514 patients who had a sepsis episode during the study, 60.5% were White (n = 2,126) and 20.9% were Black (n = 736). Overall mortality was 1.65%, but that included 3.13% of Black children versus 1.27% of White children (odds ratio [OR] 2.51, P = .001). No significant differences in mortality were seen in gender or age.

Clinical interventions in the two groups were also similar: Total IV antibiotic days were 23.8 days for Black children and 21.6 days for White children (P = .38); total vasoactive infusion days were 2.2 for Black children and 2.6 for White (P = .18); and extracorporeal membrane oxygenation was necessary for 26.1% of Black children and 18.5% of White children (P = .52).

Length of hospitalization stay, however, was an average 4 days longer for Black children (16.7 days) versus White children (12.7 days) who died (P = .03). ICU stay for Black children who died was also an average 1.9 days longer (7.57 vs. 5.7 days; P = .01). There were no significant differences in the EMR between Black and White patients, however, in the percent who were over the threshold for antibiotic administration and the percent who received an IV fluid bolus.
 

Contributing factors

Dr. Chomilo said that most BPA systems require staff – including rooming and triage staff, nurses. and physicians – to enter vital signs, order labs, enter the results into the system, and enter other data used by the algorithm. “So even though the time from when those BPA warnings flagged to when clinical interventions were documented didn’t show a significant difference, there are numerous other points along a child’s illness that may be contributing to these numbers,” Dr. Chomilo said.

For example, he pointed out that differences in health insurance coverage could have influenced whether their parent or caregiver was able to bring them in early enough to be diagnosed since studies have revealed disparate access to regular care due to structural racism in the health care system. Studies have also shown disparate rates of patients being triaged or having to wait longer in emergency departments, he added.

“When the child was brought in, how were they triaged? How long did they wait before they had vitals taken? How long until they were seen by a clinician?” Dr. Chomilo said. “Was their care on the inpatient ward the same or different? What was the source of sepsis? Was it all infectious or other issues [since] cancer and autoimmune illnesses can also trigger a sepsis evaluation, for example? Overall, I suspect answers to several of these questions would reveal a disparity due to structural racism that contributed to the ultimate disparity in deaths.”

Other social determinants of health that could have played a role in the outcome disparities here might include the family’s access to transportation options, parental employment or child care options, and nutrition access since baseline nutritional status can be a factor in the outcomes of severe illnesses like sepsis.

”I don’t think this study provided enough information about the potential causative factors to come to any strong conclusions,” Dr. Chomilo said. But it’s important for clinicians to be aware of how biases in the health care system put Black, Indigenous and other communities at higher risk for worse clinical outcomes.

“I would reiterate that clinicians in the hospital can help improve outcomes by being aware of structural racism and structural inequity and how that may contribute to their patient’s risk of severe illness as the decide how to approach their treatment and engaging the patient’s family,” Dr. Chomilo said. “We cannot rely solely on universal tools that don’t take this into account when we are looking to improve clinical outcomes for everyone. Otherwise we will see these gaps persist.”

No external funding sources were noted. Dr. Stroud and Dr. Chomilo had no disclosures.

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

People who want to be tested for chlamydia and gonorrhea are now able to do so without leaving their homes.

Called Simple 2, it’s the first test approved by the Food and Drug Administration that uses a sample collected at home to test for an STD, other than tests for HIV. The test can be purchased over-the-counter in stores or ordered online and delivered in discreet packaging. A vaginal swab or urine sample is collected and then sent for laboratory testing using a prepaid shipping label.

The FDA issued the final needed approval on Nov. 15, and the product is already for sale on the website of the manufacturer, LetsGetChecked. The listed price is $99 with free shipping for a single test kit, and the site offers a discounted subscription to receive a kit every 3 months for $69.30 per kit.

Gonorrhea cases have surged 28% since 2017, reaching 700,000 cases during 2021, Centers for Disease Control and Prevention data show. Chlamydia has also been on the rise, up 4% from 2020 to 2021, with 1.6 million annual infections.

Previously, tests for the two STDs required that samples be taken at a health care location such as a doctor’s office. The Simple 2 test results can be retrieved online, and a health care provider will reach out to people whose tests are positive or invalid. Results are typically received in 2-5 days, according to a press release from LetsGetChecked, which also offers treatment services.

“This authorization marks an important public health milestone, giving patients more information about their health from the privacy of their own home,” said Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a statement. “We are eager to continue supporting greater consumer access to diagnostic tests, which helps further our goal of bringing more health care into the home.”

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

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

BOSTON – Patients with metabolic-associated steatotic liver disease (MASLD, formerly NAFLD) without cirrhosis who took daily low-dose aspirin in a double-blind randomized trial demonstrated significant reductions in liver fat content over 6 months compared with similar patients who took a placebo, study results show.

“In MASLD without cirrhosis, low-dose aspirin, 81 milligrams daily, led to decreases in liver fat and improved markers of hepatic inflammation and fibrosis,” reported Robert M. Wilechansky, MD, a transplant hepatology fellow at Massachusetts General Hospital in Boston.

“It was safe and well tolerated in this study, but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD,” he said at the annual meeting of the American Association for the Study of Liver Diseases.

“We don’t have current plans, to my knowledge, to test full-dose aspirin,” he said in an interview. “I’m encouraged by the results with low-dose aspirin, and I think that, given the risk profile, using a lower dose is preferable.”
 

Reduction in inflammation

Although promising therapies for MASLD are in development, none are currently approved by the Food and Drug Administration, prompting Dr. Wilechansky and colleagues to investigate aspirin, with its anti-inflammatory properties, as a potential treatment.

In preclinical studies, aspirin has been shown to have both anti-inflammatory and antitumor effects in the liver through inhibition of cycloxygenase-2 and platelet-derived growth factor signaling, as well as through modulation of bioactive lipids, Dr. Wilechansky said.

In observational studies, use of aspirin was associated with a reduction in the prevalence of hepatic steatosis and fibrosis progression in patients with MASLD, and there was a decrease in the incidence of hepatocellular carcinoma and liver-related mortality among patients with viral hepatitis, he noted.

As for the potential mechanism of action of aspirin for patients with MASLD, Dr. Wilechansky noted that there may be some reduction in steatosis, and “if there is a reduction in inflammation, we may see some reduction in steatohepatitis.”
 

Study details

To see whether the so-called “wonder drug” could work wonders for patients with MASLD without cirrhosis, the researchers recruited 80 adults with MASLD and randomly assigned them to receive either aspirin 81 mg once daily or placebo for 6 months.

Patients with baseline cirrhosis or other liver disease, heavy drinkers, those who had used aspirin within 6 months, or those who used other antiplatelet or anticoagulant agents were excluded, as were patients with severe renal or cardiovascular disease, active cancer, pregnancy, were breastfeeding, had thrombocytopenia, or had undergone bariatric surgery within the past 2 years.

At baseline, 36.3% of all patients had F2-F3 fibrosis, as determined by vibration-controlled transient elastography (VCTE), and of 44 patients who had previously undergone liver biopsy, 37 (84.1%) were confirmed to have steatohepatitis.

At 6 months, the absolute change in hepatic fat fraction (HFF) from baseline, the primary endpoint, was a decline of 6.1% for patients taking aspirin, compared with a 4.2% increase for patients taking placebo, which translates into a 10.3% difference in favor of aspirin (P = .009).

The relative change in HFF, a secondary endpoint, for aspirin versus placebo was –59.2% (P = .003).

In addition, the use of aspirin was associated with a relative reduction in HFF of at least 30% among 16 of the 40 patients who received it.

Aspirin was significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction, with –2.9% versus placebo (P = .018), and the relative change in hepatic fat by MRI-PDFF, with a difference of –24.8% versus placebo (P = .009).

Aspirin was also associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

About one-third of patients in each study arm had at least one adverse event. There was only one aspirin-related adverse event (heartburn) that led to discontinuation. There were no serious bleeding events in either arm.

“We’re going to have to consider stratifying by aspirin use now in our trials,” said Mark Hartman, MD, from Eli Lilly in Indianapolis.
 

Significant weight gain in placebo group

Mary E. McCarthy Rinella, MD, FAASLD, professor of medicine at the University of Chicago, commented that the 4% increase in liver fat in the control arm “is kind of a lot for a placebo, and I’m wondering how much that accounts for the [difference] that you saw.” Dr. Rinella served as a comoderator of the session.

Dr. Wilechansky said that there were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.

A post hoc analysis suggested that most of the increase in hepatic fat among patients who took placebo could have been among that handful of patients, he added. When those patients were removed in an adjusted analysis, the difference between the aspirin and placebo groups was smaller but remained significant.

The trial was sponsored by Massachusetts General Hospital. Dr. Wilechansky, Dr. Rinella, and Dr. Hartman had no relevant disclosures.

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

Use of a standard algorithm significantly reduced the time from decision to incision in urgent, unscheduled cesarean deliveries, based on data from more than 600 procedures.

No specific recommended decision-to-incision time exists for cases of unscheduled, nonemergent cesarean deliveries, although a target of 30 minutes is recommended for emergent deliveries, Lina T. Bernal, MD, of Boston University and colleagues wrote.

The researchers developed a quality improvement project in which a multidisciplinary team defined which unscheduled cesarean deliveries should qualify as urgent, and identified a goal of 40 minutes or less for decision-to-incision time in these cases.

“We defined urgent, unscheduled cesarean delivery as cesarean delivery in patients with the following diagnoses: active phase arrest at 6 cm or greater, category II fetal heart rate tracing during labor requiring delivery per the Shields algorithm, but not meeting emergent category III criteria, any unscheduled cesarean delivery complicated by chorioamnionitis, and failed trial of labor after cesarean,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers compared times from decision to incision before and after the implementation of a multidisciplinary algorithm. The study included 199 urgent, unscheduled deliveries in a single center between May 2019 and November 2019, and implementation period with 283 deliveries from December 2019 to September 2020, and a postimplementation period with 160 deliveries between October 2020 and May 2021.

The primary outcome was the mean time from decision to incision; secondary outcomes were neonatal status based on 5-minute Apgar score and quantitative blood loss during delivery.

Overall, the mean decision-to-incision time improved from 88 minutes during the preimplementation period to 50 minutes in the postimplementation period.

For Black non-Hispanic patients, the mean decision-to-incision time improved from 98 minutes during the preimplementation period to 50 minutes in the postimplementation period. Similarly, mean times among Hispanic patients decreased from 84 minutes to 49 minutes during the pre- and postimplementation periods, respectively.

No significant improvement in decision-to-incision time was noted among patients in other racial and ethnic groups.

In cases of cesarean delivery for fetal indications, 5-minute Apgar scores were significantly higher in the postimplementation period compared with the preimplementation period (8.5 vs. 8.8, P < .01).

No significant associations appeared between maternal quantitative blood loss and the implementation of the algorithm across treatment periods.

Over the course of the study, adjustments to the algorithm included clarification of the criteria, streamlined communication, and expanded use of resources. “There are no prior studies regarding the effects of creation of an urgent category on decision-to-incision time or maternal or neonatal outcomes,” the researchers wrote. “As a result of improved outcomes and appreciation of a standardized approach, the urgent cesarean delivery designation has been incorporated into the labor unit work flow.”

The findings were limited by several factors including the retrospective design, use of data from a single medical center, and the inability to address confounding variables such as age, parity, body mass index, time of delivery, and staffing, the researchers noted. Other limitations include a lack of data on measures of maternal morbidity beyond quantitative blood loss and other neonatal morbidities, and lack of data on patient satisfaction.

However, the results support the use of a standard algorithm to successfully reduce decision-to-incision time in urgent and unscheduled cesarean deliveries, and next steps for further improvement of care should identify which patients are most likely to benefit from a more rapid delivery, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Use of a standard algorithm significantly reduced the time from decision to incision in urgent, unscheduled cesarean deliveries, based on data from more than 600 procedures.

No specific recommended decision-to-incision time exists for cases of unscheduled, nonemergent cesarean deliveries, although a target of 30 minutes is recommended for emergent deliveries, Lina T. Bernal, MD, of Boston University and colleagues wrote.

The researchers developed a quality improvement project in which a multidisciplinary team defined which unscheduled cesarean deliveries should qualify as urgent, and identified a goal of 40 minutes or less for decision-to-incision time in these cases.

“We defined urgent, unscheduled cesarean delivery as cesarean delivery in patients with the following diagnoses: active phase arrest at 6 cm or greater, category II fetal heart rate tracing during labor requiring delivery per the Shields algorithm, but not meeting emergent category III criteria, any unscheduled cesarean delivery complicated by chorioamnionitis, and failed trial of labor after cesarean,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers compared times from decision to incision before and after the implementation of a multidisciplinary algorithm. The study included 199 urgent, unscheduled deliveries in a single center between May 2019 and November 2019, and implementation period with 283 deliveries from December 2019 to September 2020, and a postimplementation period with 160 deliveries between October 2020 and May 2021.

The primary outcome was the mean time from decision to incision; secondary outcomes were neonatal status based on 5-minute Apgar score and quantitative blood loss during delivery.

Overall, the mean decision-to-incision time improved from 88 minutes during the preimplementation period to 50 minutes in the postimplementation period.

For Black non-Hispanic patients, the mean decision-to-incision time improved from 98 minutes during the preimplementation period to 50 minutes in the postimplementation period. Similarly, mean times among Hispanic patients decreased from 84 minutes to 49 minutes during the pre- and postimplementation periods, respectively.

No significant improvement in decision-to-incision time was noted among patients in other racial and ethnic groups.

In cases of cesarean delivery for fetal indications, 5-minute Apgar scores were significantly higher in the postimplementation period compared with the preimplementation period (8.5 vs. 8.8, P < .01).

No significant associations appeared between maternal quantitative blood loss and the implementation of the algorithm across treatment periods.

Over the course of the study, adjustments to the algorithm included clarification of the criteria, streamlined communication, and expanded use of resources. “There are no prior studies regarding the effects of creation of an urgent category on decision-to-incision time or maternal or neonatal outcomes,” the researchers wrote. “As a result of improved outcomes and appreciation of a standardized approach, the urgent cesarean delivery designation has been incorporated into the labor unit work flow.”

The findings were limited by several factors including the retrospective design, use of data from a single medical center, and the inability to address confounding variables such as age, parity, body mass index, time of delivery, and staffing, the researchers noted. Other limitations include a lack of data on measures of maternal morbidity beyond quantitative blood loss and other neonatal morbidities, and lack of data on patient satisfaction.

However, the results support the use of a standard algorithm to successfully reduce decision-to-incision time in urgent and unscheduled cesarean deliveries, and next steps for further improvement of care should identify which patients are most likely to benefit from a more rapid delivery, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Use of a standard algorithm significantly reduced the time from decision to incision in urgent, unscheduled cesarean deliveries, based on data from more than 600 procedures.

No specific recommended decision-to-incision time exists for cases of unscheduled, nonemergent cesarean deliveries, although a target of 30 minutes is recommended for emergent deliveries, Lina T. Bernal, MD, of Boston University and colleagues wrote.

The researchers developed a quality improvement project in which a multidisciplinary team defined which unscheduled cesarean deliveries should qualify as urgent, and identified a goal of 40 minutes or less for decision-to-incision time in these cases.

“We defined urgent, unscheduled cesarean delivery as cesarean delivery in patients with the following diagnoses: active phase arrest at 6 cm or greater, category II fetal heart rate tracing during labor requiring delivery per the Shields algorithm, but not meeting emergent category III criteria, any unscheduled cesarean delivery complicated by chorioamnionitis, and failed trial of labor after cesarean,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers compared times from decision to incision before and after the implementation of a multidisciplinary algorithm. The study included 199 urgent, unscheduled deliveries in a single center between May 2019 and November 2019, and implementation period with 283 deliveries from December 2019 to September 2020, and a postimplementation period with 160 deliveries between October 2020 and May 2021.

The primary outcome was the mean time from decision to incision; secondary outcomes were neonatal status based on 5-minute Apgar score and quantitative blood loss during delivery.

Overall, the mean decision-to-incision time improved from 88 minutes during the preimplementation period to 50 minutes in the postimplementation period.

For Black non-Hispanic patients, the mean decision-to-incision time improved from 98 minutes during the preimplementation period to 50 minutes in the postimplementation period. Similarly, mean times among Hispanic patients decreased from 84 minutes to 49 minutes during the pre- and postimplementation periods, respectively.

No significant improvement in decision-to-incision time was noted among patients in other racial and ethnic groups.

In cases of cesarean delivery for fetal indications, 5-minute Apgar scores were significantly higher in the postimplementation period compared with the preimplementation period (8.5 vs. 8.8, P < .01).

No significant associations appeared between maternal quantitative blood loss and the implementation of the algorithm across treatment periods.

Over the course of the study, adjustments to the algorithm included clarification of the criteria, streamlined communication, and expanded use of resources. “There are no prior studies regarding the effects of creation of an urgent category on decision-to-incision time or maternal or neonatal outcomes,” the researchers wrote. “As a result of improved outcomes and appreciation of a standardized approach, the urgent cesarean delivery designation has been incorporated into the labor unit work flow.”

The findings were limited by several factors including the retrospective design, use of data from a single medical center, and the inability to address confounding variables such as age, parity, body mass index, time of delivery, and staffing, the researchers noted. Other limitations include a lack of data on measures of maternal morbidity beyond quantitative blood loss and other neonatal morbidities, and lack of data on patient satisfaction.

However, the results support the use of a standard algorithm to successfully reduce decision-to-incision time in urgent and unscheduled cesarean deliveries, and next steps for further improvement of care should identify which patients are most likely to benefit from a more rapid delivery, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Making medications more accessible to those who need them is the focus of attention in the media and in all levels of government. For a drug to be accessible, it must be affordable and available. Something may be affordable, but if it isn’t available, no one will have access to it. Think of toilet paper in the first year of the COVID pandemic. The opposite is also true. An item may be available, but if it isn’t affordable, access is lost. While medication affordability is viewed as the major problem for patients, lack of availability has begun to creep into our drug supply chain. We are now experiencing drug shortages for medications that are very affordable. The perverse incentives, inherent in formulary construction, favor higher-priced medications, which decreases the availability of lower-priced – yet still expensive – drugs, thus increasing patient cost share. Formulary placement and patient cost share, important determinants of accessibility, are controlled by health plans and differ considerably even from the same payer. And yet, the price of drugs remains the target of most approaches to increasing patients’ access. And now price negotiations and drug affordability boards enter into the picture.

What are prescription drug affordability boards?

Both state and federal legislatures have placed the affordability of medications front and center on their agendas. However, neither are considering how formulary construction affects patient’s access to medications. The Inflation Reduction Act is Congress’s foray into price setting/negotiation of expensive drugs. Over the last few years, states are also attempting to make drugs more affordable by creating prescription drug affordability boards (PDABs). Governors (or other state leaders) appoint PDAB members who are charged with the task of evaluating the affordability of certain drugs for both the state and its residents. How to do it, and what the limitations are, vary from state to state. In 2019, Maryland was first state to establish a PDAB, charging its members to study commercial insurance and drug pricing and make recommendations on how to make drugs more affordable for Maryland residents. Other states that have passed PDAB legislation are Colorado, Maine, Minnesota, New Hampshire, Ohio, Oregon, and Washington.

Colorado, Minnesota, and Washington – and soon Maryland and Oregon – hope to make drugs more affordable for patients by allowing their PDABs to set an upper payment limit (UPL). A UPL serves as a cap on the sales price and reimbursement for a drug. The Michigan legislature is actively debating legislation that would establish a PDAB and allow it to set UPLs. On the surface, this may appear to be a potential solution to the affordability issue. However, as always, there are many questions as to how this will work and what are the unintended consequences of price setting and establishing UPLs for medications. UPLs have the potential to harm access to provider-administered drugs. With the help of advocacy from the Coalition of State Rheumatology Organizations (CSRO), Washington’s PDAB statute potentially has a carve-out for provider-administered drugs.
 

Possible unintended consequences for provider-administered drugs

CSRO asked for a meeting with the Colorado PDAB after they announced their list of drugs for which UPLs would be set. We spoke with the PDAB in October, hoping to point out some of the unintended consequences that needed to be considered. One of the big questions we have revolves around the “buy and bill” provider-administered drugs. According to the language of the Colorado statute, providers would not be paid any more than the UPL for a drug administered in their office. CSRO is concerned that this would leave providers uncompensated for the service of administering the drug and associated overhead. This is not to mention that providers may not be able to find a group purchasing organization that would even sell the drug at the UPL, much less a lower price than the UPL. And even if a provider could buy it at the UPL, that would mean there would be no margin to cover the overhead for their infusion suite. Interestingly, while Colorado’s rules for the UPL state that pharmacies can be paid an additional reasonable dispensing fee beyond the UPL, no such allowance is made for providers administering one of these medications. In fact, the Colorado PDAB specifically indicated that the goal of the state’s UPL methodology was to ensure that there was no “delta” between what is paid for the drug by the provider and what is reimbursed to a provider for the drug by the payer. This may cause some providers to be unable to “afford” to administer those drugs with UPLs, which ultimately reduces access for residents of Colorado to that particular medication. This is the exact opposite of what the PDAB is supposed to accomplish.

There are still many questions. What impact will UPLs have on a medication’s placement on a formulary? As we know, preferred formulary placement is often given to drugs with the highest price concession from the manufacturers. Will setting a UPL on payment for specialty pharmacy drugs to pharmacy benefit manager-owned specialty pharmacies affect that drug’s ability to be on the formulary? And again, how will the PDAB resolve the issue of compensating the provider for overhead costs associated with administering the medication?

Even more confusing questions remain. How will the UPL be enforced when a “purchase” or “sale” of the drug is made by an out-of-state entity somewhere along the supply chain? When ultimately the drug is purchased and delivered to a Colorado consumer by a Colorado provider/pharmacy, there are multiple points of the supply chain that may be outside of the jurisdiction of Colorado to enforce the UPL. This would create a misalignment in pricing among various supply chain entities.

While the sentiment behind creating PDABs is noble, it may end up having the unintended consequence of patients losing access to these drugs because of the perverse incentives involved in formulary construction or providers’ inability to afford to offer provider-administered drugs with UPLs.

Remember, expensive specialty pharmacy medications are already discounted greatly by manufacturers, often more than 50% to pharmacy benefit managers; and yet those cost savings are not passed on to the patients. Also, there is no oversight of 340B hospital contracted pharmacies to make sure that they pass those savings on to needy patients. Perhaps PDABs should address those issues, as well, if patient access to expensive medications is the goal.

Clearly, there are no easy answers. But with so many variables in the drug supply chain affecting patient access, concentrating only on one aspect may end up causing more harm than good. If your state is thinking of passing a PDAB, please let your legislators know that there are issues with this type of legislation that perhaps should be worked out before the bill is passed.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Making medications more accessible to those who need them is the focus of attention in the media and in all levels of government. For a drug to be accessible, it must be affordable and available. Something may be affordable, but if it isn’t available, no one will have access to it. Think of toilet paper in the first year of the COVID pandemic. The opposite is also true. An item may be available, but if it isn’t affordable, access is lost. While medication affordability is viewed as the major problem for patients, lack of availability has begun to creep into our drug supply chain. We are now experiencing drug shortages for medications that are very affordable. The perverse incentives, inherent in formulary construction, favor higher-priced medications, which decreases the availability of lower-priced – yet still expensive – drugs, thus increasing patient cost share. Formulary placement and patient cost share, important determinants of accessibility, are controlled by health plans and differ considerably even from the same payer. And yet, the price of drugs remains the target of most approaches to increasing patients’ access. And now price negotiations and drug affordability boards enter into the picture.

What are prescription drug affordability boards?

Both state and federal legislatures have placed the affordability of medications front and center on their agendas. However, neither are considering how formulary construction affects patient’s access to medications. The Inflation Reduction Act is Congress’s foray into price setting/negotiation of expensive drugs. Over the last few years, states are also attempting to make drugs more affordable by creating prescription drug affordability boards (PDABs). Governors (or other state leaders) appoint PDAB members who are charged with the task of evaluating the affordability of certain drugs for both the state and its residents. How to do it, and what the limitations are, vary from state to state. In 2019, Maryland was first state to establish a PDAB, charging its members to study commercial insurance and drug pricing and make recommendations on how to make drugs more affordable for Maryland residents. Other states that have passed PDAB legislation are Colorado, Maine, Minnesota, New Hampshire, Ohio, Oregon, and Washington.

Colorado, Minnesota, and Washington – and soon Maryland and Oregon – hope to make drugs more affordable for patients by allowing their PDABs to set an upper payment limit (UPL). A UPL serves as a cap on the sales price and reimbursement for a drug. The Michigan legislature is actively debating legislation that would establish a PDAB and allow it to set UPLs. On the surface, this may appear to be a potential solution to the affordability issue. However, as always, there are many questions as to how this will work and what are the unintended consequences of price setting and establishing UPLs for medications. UPLs have the potential to harm access to provider-administered drugs. With the help of advocacy from the Coalition of State Rheumatology Organizations (CSRO), Washington’s PDAB statute potentially has a carve-out for provider-administered drugs.
 

Possible unintended consequences for provider-administered drugs

CSRO asked for a meeting with the Colorado PDAB after they announced their list of drugs for which UPLs would be set. We spoke with the PDAB in October, hoping to point out some of the unintended consequences that needed to be considered. One of the big questions we have revolves around the “buy and bill” provider-administered drugs. According to the language of the Colorado statute, providers would not be paid any more than the UPL for a drug administered in their office. CSRO is concerned that this would leave providers uncompensated for the service of administering the drug and associated overhead. This is not to mention that providers may not be able to find a group purchasing organization that would even sell the drug at the UPL, much less a lower price than the UPL. And even if a provider could buy it at the UPL, that would mean there would be no margin to cover the overhead for their infusion suite. Interestingly, while Colorado’s rules for the UPL state that pharmacies can be paid an additional reasonable dispensing fee beyond the UPL, no such allowance is made for providers administering one of these medications. In fact, the Colorado PDAB specifically indicated that the goal of the state’s UPL methodology was to ensure that there was no “delta” between what is paid for the drug by the provider and what is reimbursed to a provider for the drug by the payer. This may cause some providers to be unable to “afford” to administer those drugs with UPLs, which ultimately reduces access for residents of Colorado to that particular medication. This is the exact opposite of what the PDAB is supposed to accomplish.

There are still many questions. What impact will UPLs have on a medication’s placement on a formulary? As we know, preferred formulary placement is often given to drugs with the highest price concession from the manufacturers. Will setting a UPL on payment for specialty pharmacy drugs to pharmacy benefit manager-owned specialty pharmacies affect that drug’s ability to be on the formulary? And again, how will the PDAB resolve the issue of compensating the provider for overhead costs associated with administering the medication?

Even more confusing questions remain. How will the UPL be enforced when a “purchase” or “sale” of the drug is made by an out-of-state entity somewhere along the supply chain? When ultimately the drug is purchased and delivered to a Colorado consumer by a Colorado provider/pharmacy, there are multiple points of the supply chain that may be outside of the jurisdiction of Colorado to enforce the UPL. This would create a misalignment in pricing among various supply chain entities.

While the sentiment behind creating PDABs is noble, it may end up having the unintended consequence of patients losing access to these drugs because of the perverse incentives involved in formulary construction or providers’ inability to afford to offer provider-administered drugs with UPLs.

Remember, expensive specialty pharmacy medications are already discounted greatly by manufacturers, often more than 50% to pharmacy benefit managers; and yet those cost savings are not passed on to the patients. Also, there is no oversight of 340B hospital contracted pharmacies to make sure that they pass those savings on to needy patients. Perhaps PDABs should address those issues, as well, if patient access to expensive medications is the goal.

Clearly, there are no easy answers. But with so many variables in the drug supply chain affecting patient access, concentrating only on one aspect may end up causing more harm than good. If your state is thinking of passing a PDAB, please let your legislators know that there are issues with this type of legislation that perhaps should be worked out before the bill is passed.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Making medications more accessible to those who need them is the focus of attention in the media and in all levels of government. For a drug to be accessible, it must be affordable and available. Something may be affordable, but if it isn’t available, no one will have access to it. Think of toilet paper in the first year of the COVID pandemic. The opposite is also true. An item may be available, but if it isn’t affordable, access is lost. While medication affordability is viewed as the major problem for patients, lack of availability has begun to creep into our drug supply chain. We are now experiencing drug shortages for medications that are very affordable. The perverse incentives, inherent in formulary construction, favor higher-priced medications, which decreases the availability of lower-priced – yet still expensive – drugs, thus increasing patient cost share. Formulary placement and patient cost share, important determinants of accessibility, are controlled by health plans and differ considerably even from the same payer. And yet, the price of drugs remains the target of most approaches to increasing patients’ access. And now price negotiations and drug affordability boards enter into the picture.

What are prescription drug affordability boards?

Both state and federal legislatures have placed the affordability of medications front and center on their agendas. However, neither are considering how formulary construction affects patient’s access to medications. The Inflation Reduction Act is Congress’s foray into price setting/negotiation of expensive drugs. Over the last few years, states are also attempting to make drugs more affordable by creating prescription drug affordability boards (PDABs). Governors (or other state leaders) appoint PDAB members who are charged with the task of evaluating the affordability of certain drugs for both the state and its residents. How to do it, and what the limitations are, vary from state to state. In 2019, Maryland was first state to establish a PDAB, charging its members to study commercial insurance and drug pricing and make recommendations on how to make drugs more affordable for Maryland residents. Other states that have passed PDAB legislation are Colorado, Maine, Minnesota, New Hampshire, Ohio, Oregon, and Washington.

Colorado, Minnesota, and Washington – and soon Maryland and Oregon – hope to make drugs more affordable for patients by allowing their PDABs to set an upper payment limit (UPL). A UPL serves as a cap on the sales price and reimbursement for a drug. The Michigan legislature is actively debating legislation that would establish a PDAB and allow it to set UPLs. On the surface, this may appear to be a potential solution to the affordability issue. However, as always, there are many questions as to how this will work and what are the unintended consequences of price setting and establishing UPLs for medications. UPLs have the potential to harm access to provider-administered drugs. With the help of advocacy from the Coalition of State Rheumatology Organizations (CSRO), Washington’s PDAB statute potentially has a carve-out for provider-administered drugs.
 

Possible unintended consequences for provider-administered drugs

CSRO asked for a meeting with the Colorado PDAB after they announced their list of drugs for which UPLs would be set. We spoke with the PDAB in October, hoping to point out some of the unintended consequences that needed to be considered. One of the big questions we have revolves around the “buy and bill” provider-administered drugs. According to the language of the Colorado statute, providers would not be paid any more than the UPL for a drug administered in their office. CSRO is concerned that this would leave providers uncompensated for the service of administering the drug and associated overhead. This is not to mention that providers may not be able to find a group purchasing organization that would even sell the drug at the UPL, much less a lower price than the UPL. And even if a provider could buy it at the UPL, that would mean there would be no margin to cover the overhead for their infusion suite. Interestingly, while Colorado’s rules for the UPL state that pharmacies can be paid an additional reasonable dispensing fee beyond the UPL, no such allowance is made for providers administering one of these medications. In fact, the Colorado PDAB specifically indicated that the goal of the state’s UPL methodology was to ensure that there was no “delta” between what is paid for the drug by the provider and what is reimbursed to a provider for the drug by the payer. This may cause some providers to be unable to “afford” to administer those drugs with UPLs, which ultimately reduces access for residents of Colorado to that particular medication. This is the exact opposite of what the PDAB is supposed to accomplish.

There are still many questions. What impact will UPLs have on a medication’s placement on a formulary? As we know, preferred formulary placement is often given to drugs with the highest price concession from the manufacturers. Will setting a UPL on payment for specialty pharmacy drugs to pharmacy benefit manager-owned specialty pharmacies affect that drug’s ability to be on the formulary? And again, how will the PDAB resolve the issue of compensating the provider for overhead costs associated with administering the medication?

Even more confusing questions remain. How will the UPL be enforced when a “purchase” or “sale” of the drug is made by an out-of-state entity somewhere along the supply chain? When ultimately the drug is purchased and delivered to a Colorado consumer by a Colorado provider/pharmacy, there are multiple points of the supply chain that may be outside of the jurisdiction of Colorado to enforce the UPL. This would create a misalignment in pricing among various supply chain entities.

While the sentiment behind creating PDABs is noble, it may end up having the unintended consequence of patients losing access to these drugs because of the perverse incentives involved in formulary construction or providers’ inability to afford to offer provider-administered drugs with UPLs.

Remember, expensive specialty pharmacy medications are already discounted greatly by manufacturers, often more than 50% to pharmacy benefit managers; and yet those cost savings are not passed on to the patients. Also, there is no oversight of 340B hospital contracted pharmacies to make sure that they pass those savings on to needy patients. Perhaps PDABs should address those issues, as well, if patient access to expensive medications is the goal.

Clearly, there are no easy answers. But with so many variables in the drug supply chain affecting patient access, concentrating only on one aspect may end up causing more harm than good. If your state is thinking of passing a PDAB, please let your legislators know that there are issues with this type of legislation that perhaps should be worked out before the bill is passed.
 

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].