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ATA risk stratification for DTC performs well in real-world cohort
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
REPORTING FROM ENDO 2019
Key clinical point: in a cohort of high-risk patients.
Major finding: Gross extrathyroidal disease extension and high postoperative thyroglobulin levels predicted poor response (OR for excellent response, 0.26 and 0.21, respectively).
Study details: Retrospective single-center study of 236 patients with DTC meeting American Thyroid Association criteria for high risk.
Disclosures: The authors reported no external sources of funding and that they had no conflicts of interest.
Source: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
‘Fibro-fog’ confirmed with objective ambulatory testing
MILWAUKEE – Individuals with fibromyalgia had worse cognitive functioning than did a control group without fibromyalgia, according to both subjective and objective ambulatory measures.
For study participants with fibromyalgia, aggregate self-reported cognitive function over an 8-day period was poorer than for their matched controls without fibromyalgia. Objective measures of working memory, including mean and maximum error scores on a dot memory test, also were worse for the fibromyalgia group (P less than .001 for all).
Objective measures of processing speed also were slower for those with fibromyalgia, but the difference did not reach statistical significance.
These findings are “generally consistent with findings from lab-based studies of people living with [fibromyalgia], Anna Kratz, PhD, and her coauthors wrote in a poster at the scientific meeting of the American Pain Society. by using smartphone-based capture of momentary subjective and objective cognitive functioning.
In a study of 50 adults with fibromyalgia and 50 matched controls, Dr. Kratz and her colleagues at the University of Michigan, Ann Arbor, had participants complete baseline self-report and objective measures of cognitive functioning in an in-person laboratory session. Then, participants were sent home with a wrist accelerometer and a smartphone; apps on the smartphone administered objective cognitive tests as well as subjective questions about cognitive function.
Both the subjective and objective portions of the ambulatory study were completed five times daily (on waking, and on a “quasi-random” schedule throughout the day), for at least 8 days. Day 1 was considered a “training day,” and data from that day were excluded from analysis.
To assess subjective cognitive function, patients were asked to give a momentary assessment of how slow, and how foggy, their thinking was, using a 0-100 scale. These two questions were drawn from the PROMIS Applied Cognition – General Concerns item bank. Objective measures included processing speed, captured by a 16-trial exercise of matching symbol pairs. Also, working memory was tested by completing four trials of remembering the placement of three dots in a 5x5 dot matrix.
Among the participants, 88% were female. The mean age was 45 years, and about 80% of the subjects were white. Fibromyalgia patients had more pain than did their matched controls and had poorer baseline performance on four neurocognitive tasks drawn from the National Institutes of Health Toolbox. For a flanker test, a list sorting task, a dimensional change card sort test, and a pattern comparison task, mean scores for participants with fibromyalgia ranged from 39.08 to 49.76; for the control group, mean scores ranged from 43.78 to 57.36 (P less than .05 for all).
Some people with fibromyalgia report subjective diurnal variation in cognitive function, so Dr. Kratz and her coauthors were interested in tracking performance on the ambulatory cognitive tasks over the course of the day. “Diurnal patterns and associations between objective/subjective functioning were similar across the groups,” said the authors, with no hallmark diurnal pattern for the participants with fibromyalgia. Generally, participants in both groups had the highest subjective and objective levels of performance in the morning, a dip at the first reporting time, and a gradual recovery to a level somewhat below the first morning test point by the end of the day.
Dr. Kratz and her colleagues found that in both groups, “significant associations were observed between within-person momentary changes in subjective cognitive functioning and processing speed.” This association did not hold true for working memory, however.
The findings were overall generally consistent with lab-based testing of cognitive function in individuals living with fibromyalgia, the authors said.
Dr. Kratz and her colleagues reported no outside sources of funding, and reported no conflicts of interest.
SOURCE: Kratz A et al. APS 2019, Poster 117.
MILWAUKEE – Individuals with fibromyalgia had worse cognitive functioning than did a control group without fibromyalgia, according to both subjective and objective ambulatory measures.
For study participants with fibromyalgia, aggregate self-reported cognitive function over an 8-day period was poorer than for their matched controls without fibromyalgia. Objective measures of working memory, including mean and maximum error scores on a dot memory test, also were worse for the fibromyalgia group (P less than .001 for all).
Objective measures of processing speed also were slower for those with fibromyalgia, but the difference did not reach statistical significance.
These findings are “generally consistent with findings from lab-based studies of people living with [fibromyalgia], Anna Kratz, PhD, and her coauthors wrote in a poster at the scientific meeting of the American Pain Society. by using smartphone-based capture of momentary subjective and objective cognitive functioning.
In a study of 50 adults with fibromyalgia and 50 matched controls, Dr. Kratz and her colleagues at the University of Michigan, Ann Arbor, had participants complete baseline self-report and objective measures of cognitive functioning in an in-person laboratory session. Then, participants were sent home with a wrist accelerometer and a smartphone; apps on the smartphone administered objective cognitive tests as well as subjective questions about cognitive function.
Both the subjective and objective portions of the ambulatory study were completed five times daily (on waking, and on a “quasi-random” schedule throughout the day), for at least 8 days. Day 1 was considered a “training day,” and data from that day were excluded from analysis.
To assess subjective cognitive function, patients were asked to give a momentary assessment of how slow, and how foggy, their thinking was, using a 0-100 scale. These two questions were drawn from the PROMIS Applied Cognition – General Concerns item bank. Objective measures included processing speed, captured by a 16-trial exercise of matching symbol pairs. Also, working memory was tested by completing four trials of remembering the placement of three dots in a 5x5 dot matrix.
Among the participants, 88% were female. The mean age was 45 years, and about 80% of the subjects were white. Fibromyalgia patients had more pain than did their matched controls and had poorer baseline performance on four neurocognitive tasks drawn from the National Institutes of Health Toolbox. For a flanker test, a list sorting task, a dimensional change card sort test, and a pattern comparison task, mean scores for participants with fibromyalgia ranged from 39.08 to 49.76; for the control group, mean scores ranged from 43.78 to 57.36 (P less than .05 for all).
Some people with fibromyalgia report subjective diurnal variation in cognitive function, so Dr. Kratz and her coauthors were interested in tracking performance on the ambulatory cognitive tasks over the course of the day. “Diurnal patterns and associations between objective/subjective functioning were similar across the groups,” said the authors, with no hallmark diurnal pattern for the participants with fibromyalgia. Generally, participants in both groups had the highest subjective and objective levels of performance in the morning, a dip at the first reporting time, and a gradual recovery to a level somewhat below the first morning test point by the end of the day.
Dr. Kratz and her colleagues found that in both groups, “significant associations were observed between within-person momentary changes in subjective cognitive functioning and processing speed.” This association did not hold true for working memory, however.
The findings were overall generally consistent with lab-based testing of cognitive function in individuals living with fibromyalgia, the authors said.
Dr. Kratz and her colleagues reported no outside sources of funding, and reported no conflicts of interest.
SOURCE: Kratz A et al. APS 2019, Poster 117.
MILWAUKEE – Individuals with fibromyalgia had worse cognitive functioning than did a control group without fibromyalgia, according to both subjective and objective ambulatory measures.
For study participants with fibromyalgia, aggregate self-reported cognitive function over an 8-day period was poorer than for their matched controls without fibromyalgia. Objective measures of working memory, including mean and maximum error scores on a dot memory test, also were worse for the fibromyalgia group (P less than .001 for all).
Objective measures of processing speed also were slower for those with fibromyalgia, but the difference did not reach statistical significance.
These findings are “generally consistent with findings from lab-based studies of people living with [fibromyalgia], Anna Kratz, PhD, and her coauthors wrote in a poster at the scientific meeting of the American Pain Society. by using smartphone-based capture of momentary subjective and objective cognitive functioning.
In a study of 50 adults with fibromyalgia and 50 matched controls, Dr. Kratz and her colleagues at the University of Michigan, Ann Arbor, had participants complete baseline self-report and objective measures of cognitive functioning in an in-person laboratory session. Then, participants were sent home with a wrist accelerometer and a smartphone; apps on the smartphone administered objective cognitive tests as well as subjective questions about cognitive function.
Both the subjective and objective portions of the ambulatory study were completed five times daily (on waking, and on a “quasi-random” schedule throughout the day), for at least 8 days. Day 1 was considered a “training day,” and data from that day were excluded from analysis.
To assess subjective cognitive function, patients were asked to give a momentary assessment of how slow, and how foggy, their thinking was, using a 0-100 scale. These two questions were drawn from the PROMIS Applied Cognition – General Concerns item bank. Objective measures included processing speed, captured by a 16-trial exercise of matching symbol pairs. Also, working memory was tested by completing four trials of remembering the placement of three dots in a 5x5 dot matrix.
Among the participants, 88% were female. The mean age was 45 years, and about 80% of the subjects were white. Fibromyalgia patients had more pain than did their matched controls and had poorer baseline performance on four neurocognitive tasks drawn from the National Institutes of Health Toolbox. For a flanker test, a list sorting task, a dimensional change card sort test, and a pattern comparison task, mean scores for participants with fibromyalgia ranged from 39.08 to 49.76; for the control group, mean scores ranged from 43.78 to 57.36 (P less than .05 for all).
Some people with fibromyalgia report subjective diurnal variation in cognitive function, so Dr. Kratz and her coauthors were interested in tracking performance on the ambulatory cognitive tasks over the course of the day. “Diurnal patterns and associations between objective/subjective functioning were similar across the groups,” said the authors, with no hallmark diurnal pattern for the participants with fibromyalgia. Generally, participants in both groups had the highest subjective and objective levels of performance in the morning, a dip at the first reporting time, and a gradual recovery to a level somewhat below the first morning test point by the end of the day.
Dr. Kratz and her colleagues found that in both groups, “significant associations were observed between within-person momentary changes in subjective cognitive functioning and processing speed.” This association did not hold true for working memory, however.
The findings were overall generally consistent with lab-based testing of cognitive function in individuals living with fibromyalgia, the authors said.
Dr. Kratz and her colleagues reported no outside sources of funding, and reported no conflicts of interest.
SOURCE: Kratz A et al. APS 2019, Poster 117.
REPORTING FROM APS 2019
Geroscience brings bench science to the real-world problems of aging
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
REPORTING FROM ENDO 2019
Intermittent, but prolonged, calorie restriction may improve metabolic markers
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
REPORTING FROM ENDO 2019
Oxytocin dampens the brain’s food-related reward circuitry
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
REPORTING FROM ENDO 2019
Nasal testosterone gel preserves fertility in men with hypogonadism
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
REPORTING FROM ENDO 2019
NIH’s HEAL initiative seeks coordinated effort to tackle pain, addiction
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
REPORTING FROM APS 2019
In sickle cell disease, opioid prescribing starts early, study finds
MILWAUKEE – A new study of for them.
The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.
Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.
Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.
Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.
For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.
There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.
Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.
Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.
Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.
Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”
“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.
The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”
There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”
Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.
The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.
SOURCE: Crego, N. et al. APS 2019.
MILWAUKEE – A new study of for them.
The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.
Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.
Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.
Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.
For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.
There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.
Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.
Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.
Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.
Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”
“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.
The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”
There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”
Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.
The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.
SOURCE: Crego, N. et al. APS 2019.
MILWAUKEE – A new study of for them.
The Medicaid claims database analysis looked at a one-year snapshot of prescriptions filled for a variety of opioids among children and young adults in North Carolina, said Nancy Crego, PhD, in an interview at a poster session of the scientific meeting of the American Pain Society.
Dr. Crego and her colleagues at Duke University School of Nursing, Durham, N.C., studied 1,560 children and young adults aged 0-22 years with sickle cell disease who received Medicaid; in all, 586 (38%) had an opioid prescription filled during the year-long study period.
Among adolescents and young adults with sickle cell disease, outpatient opioid prescriptions were common, with increasing prescription fills seen through the middle years and young adulthood. “Opioid prescription claims were prevalent across all age groups,” wrote Dr. Crego and her associates.
Though 20% of preschoolers (87 of 428) had had a prescription filled for opioids, the rates of opioid prescribing increased with age. Of adolescents aged 15-18 years, 54% (154 of 284) had filled an opioid prescription, as had 50% (110 of 221) of those aged 19-22 years.
For the 366 school-aged children aged 6-10 years, 117 (32%) had an opioid prescription filled. The number of prescriptions filled per patient on an annual basis for this age group ranged from one to 10.
There was a wide variation in the number of prescriptions filled in all other age groups over the study period as well. For school-aged children, the range was 1 to 10, and 1 to 18 for middle schoolers aged 11-14 years. Adolescents filled from 1-30 prescriptions, and for young adults, the range was 1-24.
Though the rates of opioid prescribing increased with age, the number of doses per prescription actually fell throughout the adolescent and young adult years. In an interview at the poster presentation, Dr. Crego speculated that this decrease observed with increasing age might reflect provider concern about opioid misuse and diversion, though the study methodology didn’t allow them to examine this.
Dr. Crego said that she was surprised by the high numbers of children who were receiving opioid prescriptions in the preschool years. “I wonder what their parents are being taught about how to administer these medications” to this very young age group, she commented.
Opioids included in the claims database analysis included morphine, hydromorphone, hydrocodone, oxycodone, oxymorphone, methadone, fentanyl, codeine, and tramadol.
Children with sickle cell disease are exposed to opioids in early childhood,” Dr. Crego and her colleagues wrote in the poster, but they acknowledged that “it is unknown if this early exposure increases the risk of opioid misuse later in life in this population ... Prescribers should incorporate continuous assessments for potential misuse and abuse in all age groups.”
“Most of the data that we have on opioid prescription claims in children usually exclude chronically ill children; they’re almost all of acutely ill children, and quite a bit of it is on postoperative care,” Dr. Crego said. The current study captures early-life prescribing “for somebody who’s going to be on opioids for a lot of their life,” she noted.
The studies of opioids used for acute pain, she said, showed that parents would often “administer opioids for inappropriate indications.” She is now conducting a qualitative study investigating pharmacologic and non-pharmacologic pain interventions for children with sickle cell disease. She’s also investigating how parents decide to administer opioids: “What did they see in their child that would prompt them to give an opioid versus giving another type of analgesic?”
There are some limitations to working with a claims database, acknowledged Dr. Crego: “We don’t know about their actual use, because we don’t know how often they are taking it, but we know it’s a filled opioid prescription.”
Dr. Crego said that more work is needed to examine how parents administer opioids to their children with sickle cell disease, and to learn more about what parents are told – and what they understand – about how their child’s pain should be managed. Also, she added, more research is needed on non-pharmacologic pain management for pediatric patients with sickle cell disease.
The study was funded by the Agency for Healthcare Research and Quality. Dr. Crego and her coauthors reported no conflicts of interest.
SOURCE: Crego, N. et al. APS 2019.
REPORTING FROM APS 2019
Addressing anxiety helps youth with functional abdominal pain disorders
MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.
A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.
The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.
Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).
The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.
The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.
Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.
Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.
With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.
“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”
The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.
At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).
In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.
A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”
Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”
Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”
Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.
The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.
[email protected]
SOURCE: Cunningham N. et al. APS 2019.
MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.
A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.
The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.
Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).
The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.
The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.
Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.
Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.
With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.
“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”
The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.
At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).
In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.
A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”
Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”
Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”
Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.
The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.
[email protected]
SOURCE: Cunningham N. et al. APS 2019.
MILWAUKEE – A stepped-care approach to youth with functional abdominal pain disorders may be effective in targeting those with comorbid anxiety, according to ongoing research.
A study of 79 pediatric patients with a functional abdominal pain disorder (FAPD) and co-occurring anxiety found that those who received cognitive behavioral therapy (CBT) that included a component to address anxiety had less functional disability and anxiety than those who received treatment as usual. Pain scores also dropped, though the difference was not statistically significant.
The patients, aged 9-14 years and mostly white and female, were randomized to treatment allocation. Functional disability scores were significantly lower post-treatment for those who received the stepped therapy compared with the treatment as usual group (P less than .05, Cohen’s D = .49). This indicates a moderate effect size, said Natoshia Cunningham, PhD, speaking at the scientific meeting of the American Pain Society.
Mean scores on an anxiety rating scale also dropped below the threshold for clinical anxiety for those receiving the stepped therapy; on average, the treatment as usual group still scored above the clinical anxiety threshold after treatment (P for difference = .05).
The study, part of ongoing research, tests a hybrid online intervention, dubbed Aim to Decrease Anxiety and Pain Treatment, or ADAPT. The ADAPT program includes some common elements of CBT for anxiety that were not previously included in the pediatric pain CBT in use for the FAPD patients, she said.
The hybrid program began with two in-person sessions, each lasting one hour. These were followed by up to four web-based sessions. Patients viewed videos, read some material online, and complete activities with follow-up assessments. The web-based component was structured so that providers can see how patients fare on assessments – and even see which activities had been opened or completed. This, said Dr. Cunningham, allowed the treating provider to tailor what’s addressed in the associated weekly phone checks that accompany the online content.
Parents were also given practical, evidence-based advice to help manage their child’s FAPD. These include encouraging children to be independent in pain management, stopping “status checks,” encouraging normal school and social activities, and avoiding special privileges when pain interferes with activities.
Overall, up to 40% of pediatric functional abdominal pain patients may not respond to CBT, the most efficacious treatment known, said Dr. Cunningham, a pediatric psychologist at the University of Cincinnati. Her research indicates that comorbid anxiety may predict poor response, and that addressing anxiety improves pain and disability in this complex, common disorder.
With a brief psychosocial screening that identifies patients with anxiety, Dr. Cunningham and her colleagues can implement the targeted, partially web-based therapy strategy that tackles anxiety along with CBT for functional abdominal pain.
“Anxiety is common and related to poor outcomes,” noted Dr. Cunningham, She added that overall, half or more of individuals with chronic pain also have anxiety. Among children with FAPD, “Clinical anxiety predicts disability and poor treatment response.”
The first step, she said, was identifying the patients with FAPD who had anxiety, including those with subclinical anxiety.
At intake, children coming to the Cincinnati Children’s Hospital’s gastroenterology clinic complete anxiety screening via the Screen for Child Anxiety Related Emotional Disorders (SCARED) (Depress Anxiety. 2000;12[2]:85-91). Disability and pain are assessed by the Functional Disability Inventory and the Numeric Rating Scale (J Pediatr Psychol. 1991 Feb;16[1]:39-58).
In earlier research, Dr. Cunningham and her collaborators found a significant association between anxiety and both higher pain levels and more disability. And, clinically significant anxiety was more likely among the FAPD patients with persistent disability after six months of treatment.
A surprising finding from the screenings, said Dr. Cunningham, is that youth endorsed more anxiety symptoms in self-assessment than their parents observed. “Children are often their own best informants of their internalizing symptoms,” she said. “Not only do their parents not notice it, it may not be obvious to their providers, either.”
Since many children with FAPD have anxiety, the next question was “How do we better enhance their treatments?” she continued. To answer that question, she took one step back: “How do these youth respond to our current best practice?”
Looking at Cincinnati Children’s patients with FAPD who did – or did not – have anxiety, Dr. Cunningham found that “those who have clinical levels of anxiety don’t respond as well to CBT.” Pain-directed therapy alone, she said, “is insufficient to treat these patients.”
Together with brief screening, stepped therapy delivered via ADAPT offers promise to boost the efficacy of FAPD treatment, perhaps even in a primary care setting, said Dr. Cunningham. She and her collaborators are continuing to study comorbid anxiety and pain in youth; current work is using functional magnetic resonance imaging to examine cognitive and affective changes in patients receiving the ADAPT intervention.
The study was funded by the American Pain Society Sharon S. Keller Chronic Pain Research Grant, Cincinnati Children’s Hospital, and the National Institutes of Health. Dr. Cunningham reported no relevant conflicts of interest.
[email protected]
SOURCE: Cunningham N. et al. APS 2019.
REPORTING FROM APS 2019
In obesity-related asthma, a new hormonal target
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
REPORTING FROM ENDO 2019
