Pharmacology

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

The Food and Drug Administration has expanded an emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.

According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.

Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.

Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.

“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.

A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.

To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.

“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.

The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.

FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.

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

The Food and Drug Administration has expanded an emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.

According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.

Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.

Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.

“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.

A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.

To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.

“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.

The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.

FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.

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

The Food and Drug Administration has expanded an emergency use authorization (EUA), allowing the Pfizer-BioNTech COVID-19 booster shot for children ages 5 to 11 who are at least 5 months out from their first vaccine series.

According to the most recent data from the Centers for Disease Control and Prevention, 28.6% of children in this age group have received both initial doses of Pfizer’s COVID-19 vaccine, and 35.3% have received their first dose.

Pfizer’s vaccine trial involving 4,500 children showed few side effects among children younger than 12 who received a booster, or third dose, according to a company statement.

Pfizer asked the FDA for an amended authorization in April, after submitting data showing that a third dose in children between 5 and 11 raised antibodies targeting the Omicron variant by 36 times.

“While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer-term effects, even following initially mild disease,” FDA Commissioner Robert M. Califf, MD, said in a news release.

A study done by the New York State Department of Health showed the effectiveness of Pfizer’s two-dose vaccine series fell from 68% to 12% 4-5 months after the second dose was given to children 5 to 11 during the Omicron surge. A CDC study published in March also showed that the Pfizer shot reduced the risk of Omicron by 31% in children 5 to 11, a significantly lower rate than for kids 12 to 15, who had a 59% risk reduction after receiving two doses.

To some experts, this data suggest an even greater need for children under 12 to be eligible for a third dose.

“Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose of the vaccine in all authorized populations,” says Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research.

The CDC still needs to sign off on the shots before they can be allowed. The agency’s Advisory Committee on Immunization Practices is set to meet on May 19 to discuss boosters in this age group.

FDA advisory panels plan to meet next month to discuss allowing Pfizer’s and Moderna’s COVID-19 vaccines for children under 6 years old.

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

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

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

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

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

Something different appears to be going on when an older adult develops inflammatory bowel disease (IBD), and now researchers offer more evidence that antibiotics could be playing a role.

Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).

The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.

In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.

“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
 

Antibiotics as a contributing link

Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.

They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.

They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.

Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.

Timing made some difference.

“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.

The investigators also considered whether the antibiotic agent or infection was behind the association.

Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.

“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.

A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
 

Clinical implications

The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.

“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”

IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.

The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.

“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.

Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.

Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.

The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.

Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.

“Hopefully, we’ll have more within the next few years to report,” he said.
 

Shedding more light on older-onset IBD worldwide

“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”

IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.

The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.

For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.

“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.

Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.

“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.

“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.

The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.

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

A new study questions the conventional wisdom of using steroids and anti-inflammatory drugs like ibuprofen to treat low back pain if exercise and other nondrug therapies don’t work right away.

Those medications offer relief from acute pain but may actually increase a person’s chances of developing chronic pain, said the investigators for a study published in Science Translational Medicine. The study results indicate that inflammation is a normal part of recovering from a painful injury and that inhibiting inflammation may result in more-difficult-to-treat chronic pain.

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs,” Jeffrey Mogil, PhD, a psychology professor at McGill University, Montreal, said in a school news release. “But we found that this short-term fix could lead to longer-term problems.”

Researchers looked at low back pain because it’s so common, with 25% of U.S. adults saying they had low back pain in the previous 3 months, according to the Centers for Disease Control and Prevention. Acute back pain is defined as lasting less than 4 weeks while chronic back pain lasts more than 12 weeks.

By examining blood samples, researchers discovered that people whose low back pain was resolved had high inflammation driven by neutrophils, a type of white blood cell that helps the body fight infection, the study said.

“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” Dr. Mogil said in the news release.

The research team found that blocking neutrophils in mice prolonged pain in the animals up to 10-fold. Pain also was prolonged when the mice were given anti-inflammatory drugs and steroids, the news release says.

McGill University said other studies support the findings. The school cited an analysis of 500,000 people in the United Kingdom. The analysis found that those taking anti-inflammatory drugs for pain were more likely to have pain 2 to 10 years later.

While saying the study suggests it’s time to reconsider how pain is treated, the researchers called for clinical trials on humans, not just observations of people with low back pain.

Experts warned about accepting the results without further investigation.

“It’s intriguing but requires further study,” Steven J. Atlas, MD, director of the Primary Care Research & Quality Improvement Network at Massachusetts General Hospital, Boston, told The New York Times.

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

A new study questions the conventional wisdom of using steroids and anti-inflammatory drugs like ibuprofen to treat low back pain if exercise and other nondrug therapies don’t work right away.

Those medications offer relief from acute pain but may actually increase a person’s chances of developing chronic pain, said the investigators for a study published in Science Translational Medicine. The study results indicate that inflammation is a normal part of recovering from a painful injury and that inhibiting inflammation may result in more-difficult-to-treat chronic pain.

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs,” Jeffrey Mogil, PhD, a psychology professor at McGill University, Montreal, said in a school news release. “But we found that this short-term fix could lead to longer-term problems.”

Researchers looked at low back pain because it’s so common, with 25% of U.S. adults saying they had low back pain in the previous 3 months, according to the Centers for Disease Control and Prevention. Acute back pain is defined as lasting less than 4 weeks while chronic back pain lasts more than 12 weeks.

By examining blood samples, researchers discovered that people whose low back pain was resolved had high inflammation driven by neutrophils, a type of white blood cell that helps the body fight infection, the study said.

“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” Dr. Mogil said in the news release.

The research team found that blocking neutrophils in mice prolonged pain in the animals up to 10-fold. Pain also was prolonged when the mice were given anti-inflammatory drugs and steroids, the news release says.

McGill University said other studies support the findings. The school cited an analysis of 500,000 people in the United Kingdom. The analysis found that those taking anti-inflammatory drugs for pain were more likely to have pain 2 to 10 years later.

While saying the study suggests it’s time to reconsider how pain is treated, the researchers called for clinical trials on humans, not just observations of people with low back pain.

Experts warned about accepting the results without further investigation.

“It’s intriguing but requires further study,” Steven J. Atlas, MD, director of the Primary Care Research & Quality Improvement Network at Massachusetts General Hospital, Boston, told The New York Times.

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

A new study questions the conventional wisdom of using steroids and anti-inflammatory drugs like ibuprofen to treat low back pain if exercise and other nondrug therapies don’t work right away.

Those medications offer relief from acute pain but may actually increase a person’s chances of developing chronic pain, said the investigators for a study published in Science Translational Medicine. The study results indicate that inflammation is a normal part of recovering from a painful injury and that inhibiting inflammation may result in more-difficult-to-treat chronic pain.

“For many decades it’s been standard medical practice to treat pain with anti-inflammatory drugs,” Jeffrey Mogil, PhD, a psychology professor at McGill University, Montreal, said in a school news release. “But we found that this short-term fix could lead to longer-term problems.”

Researchers looked at low back pain because it’s so common, with 25% of U.S. adults saying they had low back pain in the previous 3 months, according to the Centers for Disease Control and Prevention. Acute back pain is defined as lasting less than 4 weeks while chronic back pain lasts more than 12 weeks.

By examining blood samples, researchers discovered that people whose low back pain was resolved had high inflammation driven by neutrophils, a type of white blood cell that helps the body fight infection, the study said.

“Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. Inflammation occurs for a reason, and it looks like it’s dangerous to interfere with it,” Dr. Mogil said in the news release.

The research team found that blocking neutrophils in mice prolonged pain in the animals up to 10-fold. Pain also was prolonged when the mice were given anti-inflammatory drugs and steroids, the news release says.

McGill University said other studies support the findings. The school cited an analysis of 500,000 people in the United Kingdom. The analysis found that those taking anti-inflammatory drugs for pain were more likely to have pain 2 to 10 years later.

While saying the study suggests it’s time to reconsider how pain is treated, the researchers called for clinical trials on humans, not just observations of people with low back pain.

Experts warned about accepting the results without further investigation.

“It’s intriguing but requires further study,” Steven J. Atlas, MD, director of the Primary Care Research & Quality Improvement Network at Massachusetts General Hospital, Boston, told The New York Times.

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

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

A complaint filed with the U.S. Department of Justice (DOJ) alleges that Alabama’s Medicaid program is illegally denying curative drug treatment for hepatitis C virus (HCV) infection to people with substance use disorder.

The complaint was filed May 9 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School, in partnership with AIDS Alabama.

It alleges that Alabama Medicaid has a policy of denying HCV treatment to people who have used illegal drugs or alcohol in the past 6 months.

CHLPI and AIDS Alabama argue that these restrictions violate the Americans With Disabilities Act, which protects people who are disabled because of substance use disorder.

“Forced sobriety policies don’t just unfairly prevent people with substance use disorder from accessing life-saving treatment; they also severely hamper public health efforts to stop the spread of the disease,” Kevin Costello, CHLPI’s litigation director, said in a statement.

“These policies are rooted in stigma, not science, and they violate antidiscrimination provisions of the Americans With Disabilities Act,” Mr. Costello said.

Filing an administrative complaint against Alabama is “an important milestone in fighting sobriety restrictions,” he added.
 

Morally wrong

Kathie Hiers, CEO of AIDS Alabama, noted that Alabama’s health outcomes are among the worst in the nation.

“Policies that prevent adequate medical care from being provided must end. HCV now has a cure, and withholding that cure from Alabamians based on a moral judgment is wrong and certainly doesn’t follow the science,” Ms. Hiers added.

Direct-acting antiviral (DAA) therapy can cure up to 99% of people living with HCV.

The complaint against Alabama Medicaid builds on CHLPI’s successful policy advocacy and litigation campaigns to expand access to DAA therapy in state Medicaid programs across the country.

Since 2017, 19 states have removed treatment restrictions that were based on drug or alcohol use. In other states, however, “severe, illegal sobriety restrictions remain,” according to CHLPI.

Alabama, Mississippi, Arkansas, South Carolina, and South Dakota still require Medicaid enrollees with HCV to prove they have not used drugs or alcohol for 6 months before they can receive treatment. Iowa, North Dakota, and West Virginia have a 3-month abstinence requirement.

The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend DAA therapy for all patients with chronic HCV infection, regardless of drug or alcohol use.

CHLPI intends to expand this “enforcement campaign” to all states where sobriety restrictions persist.

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

A complaint filed with the U.S. Department of Justice (DOJ) alleges that Alabama’s Medicaid program is illegally denying curative drug treatment for hepatitis C virus (HCV) infection to people with substance use disorder.

The complaint was filed May 9 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School, in partnership with AIDS Alabama.

It alleges that Alabama Medicaid has a policy of denying HCV treatment to people who have used illegal drugs or alcohol in the past 6 months.

CHLPI and AIDS Alabama argue that these restrictions violate the Americans With Disabilities Act, which protects people who are disabled because of substance use disorder.

“Forced sobriety policies don’t just unfairly prevent people with substance use disorder from accessing life-saving treatment; they also severely hamper public health efforts to stop the spread of the disease,” Kevin Costello, CHLPI’s litigation director, said in a statement.

“These policies are rooted in stigma, not science, and they violate antidiscrimination provisions of the Americans With Disabilities Act,” Mr. Costello said.

Filing an administrative complaint against Alabama is “an important milestone in fighting sobriety restrictions,” he added.
 

Morally wrong

Kathie Hiers, CEO of AIDS Alabama, noted that Alabama’s health outcomes are among the worst in the nation.

“Policies that prevent adequate medical care from being provided must end. HCV now has a cure, and withholding that cure from Alabamians based on a moral judgment is wrong and certainly doesn’t follow the science,” Ms. Hiers added.

Direct-acting antiviral (DAA) therapy can cure up to 99% of people living with HCV.

The complaint against Alabama Medicaid builds on CHLPI’s successful policy advocacy and litigation campaigns to expand access to DAA therapy in state Medicaid programs across the country.

Since 2017, 19 states have removed treatment restrictions that were based on drug or alcohol use. In other states, however, “severe, illegal sobriety restrictions remain,” according to CHLPI.

Alabama, Mississippi, Arkansas, South Carolina, and South Dakota still require Medicaid enrollees with HCV to prove they have not used drugs or alcohol for 6 months before they can receive treatment. Iowa, North Dakota, and West Virginia have a 3-month abstinence requirement.

The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend DAA therapy for all patients with chronic HCV infection, regardless of drug or alcohol use.

CHLPI intends to expand this “enforcement campaign” to all states where sobriety restrictions persist.

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

A complaint filed with the U.S. Department of Justice (DOJ) alleges that Alabama’s Medicaid program is illegally denying curative drug treatment for hepatitis C virus (HCV) infection to people with substance use disorder.

The complaint was filed May 9 by the Center for Health Law and Policy Innovation (CHLPI) of Harvard Law School, in partnership with AIDS Alabama.

It alleges that Alabama Medicaid has a policy of denying HCV treatment to people who have used illegal drugs or alcohol in the past 6 months.

CHLPI and AIDS Alabama argue that these restrictions violate the Americans With Disabilities Act, which protects people who are disabled because of substance use disorder.

“Forced sobriety policies don’t just unfairly prevent people with substance use disorder from accessing life-saving treatment; they also severely hamper public health efforts to stop the spread of the disease,” Kevin Costello, CHLPI’s litigation director, said in a statement.

“These policies are rooted in stigma, not science, and they violate antidiscrimination provisions of the Americans With Disabilities Act,” Mr. Costello said.

Filing an administrative complaint against Alabama is “an important milestone in fighting sobriety restrictions,” he added.
 

Morally wrong

Kathie Hiers, CEO of AIDS Alabama, noted that Alabama’s health outcomes are among the worst in the nation.

“Policies that prevent adequate medical care from being provided must end. HCV now has a cure, and withholding that cure from Alabamians based on a moral judgment is wrong and certainly doesn’t follow the science,” Ms. Hiers added.

Direct-acting antiviral (DAA) therapy can cure up to 99% of people living with HCV.

The complaint against Alabama Medicaid builds on CHLPI’s successful policy advocacy and litigation campaigns to expand access to DAA therapy in state Medicaid programs across the country.

Since 2017, 19 states have removed treatment restrictions that were based on drug or alcohol use. In other states, however, “severe, illegal sobriety restrictions remain,” according to CHLPI.

Alabama, Mississippi, Arkansas, South Carolina, and South Dakota still require Medicaid enrollees with HCV to prove they have not used drugs or alcohol for 6 months before they can receive treatment. Iowa, North Dakota, and West Virginia have a 3-month abstinence requirement.

The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend DAA therapy for all patients with chronic HCV infection, regardless of drug or alcohol use.

CHLPI intends to expand this “enforcement campaign” to all states where sobriety restrictions persist.

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

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.

Concerns about the side effects of topical corticosteroids continue to be a source of anxiety for parents of children with atopic dermatitis (AD), leading some medical providers to prescribe weaker products, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.

Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.

When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.

In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..

The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.

Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.

Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.

“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”

In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.

The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).

Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).

“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.

For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.

 

Discussing efficacy and safety
 

Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.

Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.

“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.

The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”

Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.

Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.