Heidi Splete

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

Initiating treatment may become easier for adults living with HIV. The Food and Drug Administration has approved a label update that allows adults living with HIV to begin treatment with Cabenuva, a combination injectable, without a lead-in period of oral tablets, according to a press release from Janssen Pharmaceuticals.

Cabenuva combines rilpivirine (Janssen) and cabotegravir (ViiV Healthcare). The change offers patients and clinicians an option for a streamlined entry to treatment without the burden of daily pill taking, according to the release.

Cabenuva injections may be given as few as six times a year to manage HIV, according to Janssen. HIV patients with viral suppression previously had to complete an oral treatment regimen before starting monthly or bimonthly injections.

The injectable combination of cabotegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 nonnucleoside reverse transcriptase inhibitor, is currently indicated as a complete treatment regimen to replace the current antiretroviral regimen for adults with HIV who are virologically suppressed,” according to the press release.

“Janssen and ViiV are exploring the future possibility of an ultra–long-acting version of Cabenuva, which could reduce the frequency of injections even further, according to the press release.
 

Access may improve, but barriers persist

“Despite advances in HIV care, many barriers remain, particularly for the most vulnerable populations,” Lina Rosengren-Hovee, MD, of the University of North Carolina at Chapel Hill, said in an interview.

“Care engagement has improved with the use of bridge counselors, rapid ART [antiretroviral therapy] initiation policies, and contact tracing,” she said. “Similarly, increasing access to multiple modalities of HIV treatment is critical to increase engagement in care.

“For patients, removing the oral lead-in primarily reduces the number of clinical visits to start injectable ART,” Dr. Rosengren-Hovee added. “It may also remove adherence barriers for patients who have difficulty taking a daily oral medication.”

But Dr. Rosengren-Hovee (who has no financial connection to the manufacturers) pointed out that access to Cabenuva may not be seamless. “Unless the medication is stocked in clinics, patients are not likely to receive their first injection during the initial visit. Labs are also required prior to initiation to ensure there is no contraindication to the medication, such as viral resistance to one of its components. Cost and insurance coverage are also likely to remain major obstacles.”

Dr. Rosengren-Hovee has disclosed no relevant financial relationships.

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

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

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

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

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

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

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

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

There does not appear to be superiority of any type of biologic medication for patients with rheumatoid arthritis across different body mass index (BMI) groupings, with obesity and underweight both reducing the effects of the treatments after 6 months of use, according to findings from registry data on nearly 6,000 individuals.

Although interest in the precision use of biologics for RA is on the rise, few patient characteristics have been identified to inform therapeutic decisions, Joshua F. Baker, MD, of the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, Philadelphia, and colleagues wrote.

Previous studies on the effect of obesity on RA treatments have been inconclusive, and a comparison of RA treatments across BMI categories would provide more definitive guidance, they said.

In a study published in Arthritis Care & Research, the researchers used the CorEvitas U.S. observational registry (formerly known as Corrona) to identify adults who initiated second- or third-line treatment for RA with tumor necrosis factor inhibitors (n = 2,891) or non-TNFi biologics (n = 3,010) between 2001 and April 30, 2021.

The study population included adults diagnosed with RA; those with low disease activity or without a 6-month follow-up visit were excluded. BMI was categorized as underweight (less than 18.5 kg/m²), normal weight (18.5-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), and severely obese (35 kg/m² or higher). The three measures of response were the achievement of low disease activity (LDA), a change at least as large as the minimum clinically important difference (MCID), and the absolute change on the Clinical Disease Activity Index (CDAI) from baseline.

A total of 2,712 patients were obese or severely obese at the time of treatment initiation.

Overall, patients with severe obesity had significantly lower odds of achieving either LDA or a change at least as large as the MCID, as well as less improvement in CDAI score, compared with other BMI categories. However, in adjusted models, the differences in these outcomes for patients with severe obesity were no longer statistically significant, whereas underweight was associated with lower odds of achieving LDA (odds ratio, 0.32; P = .005) or a change at least as large as the MCID (OR, 0.40; P = .005). The adjusted model also showed lesser improvement on CDAI in underweight patients, compared with patients of normal weight (P = .006).

Stratification by TNFi and non-TNFi therapies showed no differences in clinical response rates across BMI categories.

The study represents the first evidence of a similar reduction in therapeutic response with both TNFi and non-TNFi in severely obese patients, with estimates for non-TNFi biologics that fit within the 95% confidence interval for TNFi biologics, the researchers wrote. “Our current study suggests that a lack of response among obese patients is not specific to TNFi therapies, suggesting that this phenomenon is not biologically specific to the TNF pathway.”

The study findings were limited by several factors, including the focus on patients who were not naive to biologic treatments and by the relatively small number of underweight patients (n = 57), the researchers noted. Other limitations include unaddressed mediators of the relationship between obesity and disease activity and lack of data on off-label dosing strategies.

However, the results were strengthened by the large sample size, control for a range of confounding factors, and the direct comparison of RA therapies.

The researchers concluded that BMI should not influence the choice of TNF versus non-TNF therapy in terms of clinical efficacy.

The study was supported by the Corrona Research Foundation. Dr. Baker disclosed receiving support from a Veterans Affairs Clinical Science Research and Development Merit Award and a Rehabilitation Research and Development Merit Award, and consulting fees from Bristol-Myers Squibb, Pfizer, CorEvitas, and Burns-White. Two coauthors reported financial ties to CorEvitas.

There does not appear to be superiority of any type of biologic medication for patients with rheumatoid arthritis across different body mass index (BMI) groupings, with obesity and underweight both reducing the effects of the treatments after 6 months of use, according to findings from registry data on nearly 6,000 individuals.

Although interest in the precision use of biologics for RA is on the rise, few patient characteristics have been identified to inform therapeutic decisions, Joshua F. Baker, MD, of the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, Philadelphia, and colleagues wrote.

Previous studies on the effect of obesity on RA treatments have been inconclusive, and a comparison of RA treatments across BMI categories would provide more definitive guidance, they said.

In a study published in Arthritis Care & Research, the researchers used the CorEvitas U.S. observational registry (formerly known as Corrona) to identify adults who initiated second- or third-line treatment for RA with tumor necrosis factor inhibitors (n = 2,891) or non-TNFi biologics (n = 3,010) between 2001 and April 30, 2021.

The study population included adults diagnosed with RA; those with low disease activity or without a 6-month follow-up visit were excluded. BMI was categorized as underweight (less than 18.5 kg/m²), normal weight (18.5-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), and severely obese (35 kg/m² or higher). The three measures of response were the achievement of low disease activity (LDA), a change at least as large as the minimum clinically important difference (MCID), and the absolute change on the Clinical Disease Activity Index (CDAI) from baseline.

A total of 2,712 patients were obese or severely obese at the time of treatment initiation.

Overall, patients with severe obesity had significantly lower odds of achieving either LDA or a change at least as large as the MCID, as well as less improvement in CDAI score, compared with other BMI categories. However, in adjusted models, the differences in these outcomes for patients with severe obesity were no longer statistically significant, whereas underweight was associated with lower odds of achieving LDA (odds ratio, 0.32; P = .005) or a change at least as large as the MCID (OR, 0.40; P = .005). The adjusted model also showed lesser improvement on CDAI in underweight patients, compared with patients of normal weight (P = .006).

Stratification by TNFi and non-TNFi therapies showed no differences in clinical response rates across BMI categories.

The study represents the first evidence of a similar reduction in therapeutic response with both TNFi and non-TNFi in severely obese patients, with estimates for non-TNFi biologics that fit within the 95% confidence interval for TNFi biologics, the researchers wrote. “Our current study suggests that a lack of response among obese patients is not specific to TNFi therapies, suggesting that this phenomenon is not biologically specific to the TNF pathway.”

The study findings were limited by several factors, including the focus on patients who were not naive to biologic treatments and by the relatively small number of underweight patients (n = 57), the researchers noted. Other limitations include unaddressed mediators of the relationship between obesity and disease activity and lack of data on off-label dosing strategies.

However, the results were strengthened by the large sample size, control for a range of confounding factors, and the direct comparison of RA therapies.

The researchers concluded that BMI should not influence the choice of TNF versus non-TNF therapy in terms of clinical efficacy.

The study was supported by the Corrona Research Foundation. Dr. Baker disclosed receiving support from a Veterans Affairs Clinical Science Research and Development Merit Award and a Rehabilitation Research and Development Merit Award, and consulting fees from Bristol-Myers Squibb, Pfizer, CorEvitas, and Burns-White. Two coauthors reported financial ties to CorEvitas.

There does not appear to be superiority of any type of biologic medication for patients with rheumatoid arthritis across different body mass index (BMI) groupings, with obesity and underweight both reducing the effects of the treatments after 6 months of use, according to findings from registry data on nearly 6,000 individuals.

Although interest in the precision use of biologics for RA is on the rise, few patient characteristics have been identified to inform therapeutic decisions, Joshua F. Baker, MD, of the Philadelphia Veterans Affairs Medical Center and the University of Pennsylvania, Philadelphia, and colleagues wrote.

Previous studies on the effect of obesity on RA treatments have been inconclusive, and a comparison of RA treatments across BMI categories would provide more definitive guidance, they said.

In a study published in Arthritis Care & Research, the researchers used the CorEvitas U.S. observational registry (formerly known as Corrona) to identify adults who initiated second- or third-line treatment for RA with tumor necrosis factor inhibitors (n = 2,891) or non-TNFi biologics (n = 3,010) between 2001 and April 30, 2021.

The study population included adults diagnosed with RA; those with low disease activity or without a 6-month follow-up visit were excluded. BMI was categorized as underweight (less than 18.5 kg/m²), normal weight (18.5-25 kg/m²), overweight (25-30 kg/m²), obese (30-35 kg/m²), and severely obese (35 kg/m² or higher). The three measures of response were the achievement of low disease activity (LDA), a change at least as large as the minimum clinically important difference (MCID), and the absolute change on the Clinical Disease Activity Index (CDAI) from baseline.

A total of 2,712 patients were obese or severely obese at the time of treatment initiation.

Overall, patients with severe obesity had significantly lower odds of achieving either LDA or a change at least as large as the MCID, as well as less improvement in CDAI score, compared with other BMI categories. However, in adjusted models, the differences in these outcomes for patients with severe obesity were no longer statistically significant, whereas underweight was associated with lower odds of achieving LDA (odds ratio, 0.32; P = .005) or a change at least as large as the MCID (OR, 0.40; P = .005). The adjusted model also showed lesser improvement on CDAI in underweight patients, compared with patients of normal weight (P = .006).

Stratification by TNFi and non-TNFi therapies showed no differences in clinical response rates across BMI categories.

The study represents the first evidence of a similar reduction in therapeutic response with both TNFi and non-TNFi in severely obese patients, with estimates for non-TNFi biologics that fit within the 95% confidence interval for TNFi biologics, the researchers wrote. “Our current study suggests that a lack of response among obese patients is not specific to TNFi therapies, suggesting that this phenomenon is not biologically specific to the TNF pathway.”

The study findings were limited by several factors, including the focus on patients who were not naive to biologic treatments and by the relatively small number of underweight patients (n = 57), the researchers noted. Other limitations include unaddressed mediators of the relationship between obesity and disease activity and lack of data on off-label dosing strategies.

However, the results were strengthened by the large sample size, control for a range of confounding factors, and the direct comparison of RA therapies.

The researchers concluded that BMI should not influence the choice of TNF versus non-TNF therapy in terms of clinical efficacy.

The study was supported by the Corrona Research Foundation. Dr. Baker disclosed receiving support from a Veterans Affairs Clinical Science Research and Development Merit Award and a Rehabilitation Research and Development Merit Award, and consulting fees from Bristol-Myers Squibb, Pfizer, CorEvitas, and Burns-White. Two coauthors reported financial ties to CorEvitas.