Kari Oakes

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

WASHINGTON – Can early family interventions help children with sickle cell disease (SCD) stay on track for normal cognitive development?

Given the stakes – even young children with SCD have a high risk of ischemic cerebral insults, with significant downstream cognitive deficits – these interventions are sorely needed, said Allison King, MD, PhD, of Washington University, St. Louis.

Speaking at the annual meeting of the Foundation for Sickle Cell Disease Research, Dr. King shared her institution’s suite of interventions, which are aimed at giving infants and toddlers early home enrichment through parent education and engagement.

Dr. King reviewed some of the factors that are known to be associated with intelligence quotient (IQ) changes in individuals with SCD. The single largest impact comes with an overt stroke, which drops IQ by an average 10 points. A “silent” subclinical stroke is associated with a mean 5-point decrease, while hypoxemia is associated with diminution in IQ of about 0.75 points.

On the other hand, having a parent with at least some college education is associated with a robust 6-point boost in IQ, Dr. King said.

Even if the disease results in a mean 5-point drop in IQ for the national population of children with SCD, this would result in the bell curve of intellectual ability for this cohort shifting significantly to the left, Dr. King said. Instead of 6 million children with SCD falling into the “intellectually disabled” category of those with IQs less than 70, the number would climb to 9.4 million, a 57% increase.

Cognitive impairment can be evident by the toddler years. Across the literature, 46%-58% of young children with SCD have been found to have risk for developmental delay or to show frank delay by 12-36 months of age, Dr. King said. Factors associated with risk of delay include low hemoglobin level, disease phenotype, positive transcranial Doppler findings, and – importantly – parental education, income, and perceived helplessness.

Dr. King and her collaborators have tackled the home environment to address some of these potentially remediable social factors. They hypothesized that a parent education program that boosts the quality of parent-child interactions would help children with SCD have better developmental outcomes.

She and her colleagues designed a prospective single-arm pilot study that enrolled children with SCD from birth to 36 months of age, along with a parent or caregiver (Pediatr Blood Cancer. 2016 Dec;63[12]:2131-8).

Over a period of continuous enrollment of up to 2 years, the families received a monthly visit from a home educator. During these visits, the educators delivered a validated “Born to Learn” curriculum that uses a parents-as-teachers model.

Of the 35 children, 15 (43%) were female. At enrollment, the children were a mean 5 months of age and their primary caregiver was a mean 25 years old. The children’s mean age of exit from the study was 26 months. Most patients had either the HbSS (46%) or the HbSC (43%) phenotype. At enrollment, the mean peripheral oxygen saturation was 100%, and hematocrit was a mean 27.9%.

“The parenting intervention improved cognition and language,” Dr. King said, especially in the domains of cognitive performance and expressive language, which both saw significant age-normed score improvements over the course of the study (P = .016 and .002, respectively).

Among the pre- and poststudy measures that were used was the Home Observation for Measurement of Environment tool, said Dr. King. This observer-completed scale measures parent/caregiver responsivity, acceptance, and organization. Also, the parent’s level of organization and involvement is assessed, as are available learning materials and variety of resources and enrichment.

Scores improved here, too, particularly in the domains of organization and the amount of learning materials available at home (P less than .05 for both). There was a numeric improvement in the overall score, but the figure wasn’t statistically significant.

Dr. King used recent research to bring home the importance of early intervention to support cognitive development in children with SCD. A recent meta-analysis found that 50.3% of SCD patients will have had a silent brain infarct by 30 years of age (Blood. 2016 Apr 21;127[16]:2038-40). The same publication, she said, cited work that found a prevalence of silent infarcts ranging from more than 25% by the age of 5 years to 19%-28% at 8 years.

But “parent education impacts IQ more than silent infarcts,” she said. In her work, the highest predicted IQs are seen in young patients with no infarcts and whose parents have had some college education. Perhaps surprisingly, she said, the next highest IQ tier consists of patients who have detectable infarcts, but whose parents have had at least some college education. These patients’ predicted IQs were higher than those who had no infarcts but whose parents had no more than a high school education, as well as children with the double hit of an infarct and parents with no college education.

Putting these puzzle pieces together matters for long-term outcomes, Dr. King said. Socioeconomic status is the strongest predictor of grade retention for children with SCD, with the poorest quartile in a study of 536 pediatric SCD patients having an odds ratio of 6.4 for grade retention, compared with the highest quartile (P = .001). Notably, children in the lowest quartile lived in homes where the per capita income was less than $3,000 (Am J Hematol. 2014;89[10]:e188-92). This highlights the “abject poverty” many of these families face, Dr. King said.

Children in this poorest quartile, especially boys, fared poorly going forward. “By age 15, 65% of poor males with sickle cell anemia fail a grade,” Dr. King said. The frequent absenteeism occasioned by hospital stays, clinic visits, and days at home with pain mount to an average of 15-22 missed school days annually, she said, adding that “absenteeism is an important predictor of dropout.”

These trends are brought forward into the workplace, with adults who have SCD being less likely to be employed if their IQs are lower. The association is particularly strong for processing speed, according to one study (J Clin Exp Neuropsychol. 2016 Aug;38[6]:661-71).

Dr. King outlined some concrete steps that those caring for children with SCD can take to maximize their chances for school success, acknowledging that time and resource constraints will vary by practice setting. These include completing an in-clinic educational inventory, asking about recent school performance, and if indicated, referring for neuropsychology evaluation to be shared with the school.

Physicians also can work to engage institutional resources for advocacy and communication with the school.

Parents can be encouraged to request a 504 plan, a federally mandated set of accommodations. For children with SCD, these might include setting up tutoring for periods when the child is homebound, allowing a water bottle and frequent bathroom breaks since hydration is critical for children with SCD, and allowing extra time for testing if processing speed is an issue.

An additional education step is the individualized education plan, or IEP, which can include instruction in smaller groups or teaching that’s modified for special learning needs; alternative methods of assessments; and, for older children, consideration of a vocational education path to complete high school.

Dr. King reported having no conflicts of interest.
 

[email protected]

BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.

“Abnormal bone metabolism is a feature of both obesity and gastric bypass surgery,” said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.

It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.

With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.

After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).

A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.

HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.

A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.

All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.

Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).

Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.

Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.

Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.

However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).

Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.

How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.

All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.

Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.

[email protected]

BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.

“Abnormal bone metabolism is a feature of both obesity and gastric bypass surgery,” said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.

It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.

With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.

After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).

A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.

HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.

A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.

All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.

Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).

Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.

Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.

Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.

However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).

Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.

How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.

All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.

Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.

[email protected]

BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.

“Abnormal bone metabolism is a feature of both obesity and gastric bypass surgery,” said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.

It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.

With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.

After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).

A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.

HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.

A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.

All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.

Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).

Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.

Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.

Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.

However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).

Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.

How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.

All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.

Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.

[email protected]

BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

[email protected]

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

[email protected]

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

[email protected]

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

[email protected]

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

[email protected]

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

[email protected]

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

BOSTON – Semaglutide was effective in treating type 2 diabetes mellitus among all racial and ethnic subgroups studied in a series of clinical trials; the efficacy did not come at the cost of frequent hypoglycemia or other serious adverse events, according to a pooled subgroup analysis of the SUSTAIN trials.

The trials investigated the safety and efficacy of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the treatment of T2DM. Cyrus V. Desouza, MBBS, presented results of a post hoc analysis of racial and ethnic subgroups, drawing on SUSTAIN trials 1-5 and 7 (SUSTAIN 6 had a different design, focusing on cardiovascular outcomes).

“The trials incorporated patients on the whole spectrum of diabetes, starting from people who are newly diagnosed ... all the way to patients who were on a combination of oral antidiabetic drugs plus insulin,” Dr. Desouza explained in an interview at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists.

The mean time since diagnosis in the SUSTAIN trials varied from 4.2 years in SUSTAIN 1 to 13.3 years in SUSTAIN 5. Dr. Desouza and his colleagues pooled data from the six trials to conduct the subgroup analyses.

Patients in the intervention arms of all trials received once weekly subcutaneous semaglutide, at a dose of either 0.5 mg or 1.0 mg, according to Dr. Desouza, professor of diabetes, endocrinology, and metabolism and Schultz Professor of Diabetes Research, Diabetes, Endocrinology, and Metabolism at the University of Nebraska, Lincoln.

In all, data from 3,066 patients were available. In the racial analysis, 982 low- and 1,328 high-dose semaglutide recipients were white, 243 and 232 were Asian, 82 and 124 were African American, and 25 and 50 identified as “other,” respectively.

An analysis by ethnicity found that 208 low- and 324 high-dose recipients were Hispanic.

At baseline in all trials, mean hemoglobin A_1c levels were similar, ranging from 8% to 8.4%; weights at baseline were a mean 89.6 kg to 96.2 kg across the trials.

The range of reductions in HbA_1c was similar across racial and ethnic groups. “If you look at the proportion of patients who actually achieved an A_1c below 7[%], it’s pretty impressive – it’s between 70% to 80%.” Between 50% and 60% of patients reached an HbA_1c less than 6.5%, said Dr. Desouza.

Looking at the data another way, 62.2%-72.4% of patients saw an HbA_1c reduction of at least 1% on low-dose semaglutide; the range across ethnicities was 74.2%-87.1% on high-dose semaglutide. Dr. Desouza said that the sample sizes weren’t large enough to calculate statistical significance for these subgroup differences.

“But I think what is impressive is that over 50% of patients in all the races and ethnicities were able to achieve a 5% body weight loss, which is metabolically significant in terms of improving outcomes,” he said. “I think that’s a really important fact.” A smaller proportion – around 20% – lost at least 10% of body weight, mostly on high-dose semaglutide.

Severe hypoglycemia, as defined by American Diabetes Association classification, was very rare across trials, except that 4.7% of African Americans saw this adverse event on high-dose semaglutide. Incidence in other subgroups, at either dose, ranged from 0% to 2.4%.

Otherwise, the medication was generally well tolerated, though gastrointestinal side effects were seen. “Asian people have a little higher GI side effects – up to 50% of Asians did develop GI side effects, and between 10% and 13% of Asians had to stop medication due to side effects,” said Dr. Desouza. “So I think that would be the one caveat in terms of tolerance that we did learn.”

The SUSTAIN trials were sponsored by Novo Nordisk. Dr. Desouza has received consulting fees for Novo Nordisk and has received grant support from several other pharmaceutical companies. Two coauthors are Novo Nordisk employees.

[email protected]

SOURCE: Desouza C et al. AACE 2018, Abstract 298

AUSTIN, TEX. – A first look at the timing of neonatal deaths showed an association with weekend deliveries in one Texas county. However, birth weight and ethnicity attenuated the association, according to a recent study. Higher hospital volumes were associated with lower risk of neonatal deaths.

The retrospective, population-based cohort study, presented during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, used data from birth certificates and infant death certificates in the state of Texas. The investigators, said Elizabeth Restrepo, PhD, chose to examine data from Tarrant County, Tex., which has historically had persistently high infant mortality rates; in 2013, she said, the infant mortality rate in that county was 7.11/1,000 births – the highest in the state for that year.

The first question Dr. Restrepo and her colleagues at Texas Women’s University, Denton, wanted to answer was whether there was an association between the risk of neonatal mortality and the day of the week of the birth. For this and the study’s other research questions, she and her colleagues looked at 2012 data, matching 32,140 birth certificate records with 92 infant death certificates.

The investigators found an independent association between the risk of neonatal death and whether the birth happened on a weekday (Monday at 7:00 a.m. through Friday at 6:59 p.m.), or on a weekend (Friday at 7:00 p.m. through Monday at 6:59 a.m.). However, once birth weight and ethnicity were controlled in the statistical analysis, the association was not statistically significant despite an odds ratio of 1.44 (95% confidence interval, 0.911-2.27; P = .119).

“Births in the 12 hospitals studied appear to have been organized to take place more frequently on the working weekday rather than weekend days,” wrote Dr. Restrepo and her colleagues in the poster accompanying the presentation. Although the study wasn’t designed to answer this particular question, Dr. Restrepo said in discussion during the poster session that planned deliveries, such as inductions and cesarean deliveries, are likely to happen during the week, while the case mix is wider on weekends. Patient characteristics, as well as staffing patterns, may come into play.

The researchers also asked whether birth volume at a given institution increases the odds of neonatal death on weekends. Here, they found a significant inverse relationship between hospital birth volume and neonatal deaths (r = –0.021; P less than .001). With each additional increase of 1% in the weekday birth rate, the odds of neonatal death dropped by approximately 7.4%.

Examining the Tarrant County data further, Dr. Restrepo and her colleagues found that the hospitals with higher birth volumes had a more even distribution of births across the days of the week, with resulting lower concentrations of births during the week (r = –.394; P less than .001).

[email protected]

SOURCE: Restrepo E et al. ACOG 2018, Abstract 22R.

AUSTIN, TEX. – A first look at the timing of neonatal deaths showed an association with weekend deliveries in one Texas county. However, birth weight and ethnicity attenuated the association, according to a recent study. Higher hospital volumes were associated with lower risk of neonatal deaths.

The retrospective, population-based cohort study, presented during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, used data from birth certificates and infant death certificates in the state of Texas. The investigators, said Elizabeth Restrepo, PhD, chose to examine data from Tarrant County, Tex., which has historically had persistently high infant mortality rates; in 2013, she said, the infant mortality rate in that county was 7.11/1,000 births – the highest in the state for that year.

The first question Dr. Restrepo and her colleagues at Texas Women’s University, Denton, wanted to answer was whether there was an association between the risk of neonatal mortality and the day of the week of the birth. For this and the study’s other research questions, she and her colleagues looked at 2012 data, matching 32,140 birth certificate records with 92 infant death certificates.

The investigators found an independent association between the risk of neonatal death and whether the birth happened on a weekday (Monday at 7:00 a.m. through Friday at 6:59 p.m.), or on a weekend (Friday at 7:00 p.m. through Monday at 6:59 a.m.). However, once birth weight and ethnicity were controlled in the statistical analysis, the association was not statistically significant despite an odds ratio of 1.44 (95% confidence interval, 0.911-2.27; P = .119).

“Births in the 12 hospitals studied appear to have been organized to take place more frequently on the working weekday rather than weekend days,” wrote Dr. Restrepo and her colleagues in the poster accompanying the presentation. Although the study wasn’t designed to answer this particular question, Dr. Restrepo said in discussion during the poster session that planned deliveries, such as inductions and cesarean deliveries, are likely to happen during the week, while the case mix is wider on weekends. Patient characteristics, as well as staffing patterns, may come into play.

The researchers also asked whether birth volume at a given institution increases the odds of neonatal death on weekends. Here, they found a significant inverse relationship between hospital birth volume and neonatal deaths (r = –0.021; P less than .001). With each additional increase of 1% in the weekday birth rate, the odds of neonatal death dropped by approximately 7.4%.

Examining the Tarrant County data further, Dr. Restrepo and her colleagues found that the hospitals with higher birth volumes had a more even distribution of births across the days of the week, with resulting lower concentrations of births during the week (r = –.394; P less than .001).

[email protected]

SOURCE: Restrepo E et al. ACOG 2018, Abstract 22R.

AUSTIN, TEX. – A first look at the timing of neonatal deaths showed an association with weekend deliveries in one Texas county. However, birth weight and ethnicity attenuated the association, according to a recent study. Higher hospital volumes were associated with lower risk of neonatal deaths.

The retrospective, population-based cohort study, presented during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, used data from birth certificates and infant death certificates in the state of Texas. The investigators, said Elizabeth Restrepo, PhD, chose to examine data from Tarrant County, Tex., which has historically had persistently high infant mortality rates; in 2013, she said, the infant mortality rate in that county was 7.11/1,000 births – the highest in the state for that year.

The first question Dr. Restrepo and her colleagues at Texas Women’s University, Denton, wanted to answer was whether there was an association between the risk of neonatal mortality and the day of the week of the birth. For this and the study’s other research questions, she and her colleagues looked at 2012 data, matching 32,140 birth certificate records with 92 infant death certificates.

The investigators found an independent association between the risk of neonatal death and whether the birth happened on a weekday (Monday at 7:00 a.m. through Friday at 6:59 p.m.), or on a weekend (Friday at 7:00 p.m. through Monday at 6:59 a.m.). However, once birth weight and ethnicity were controlled in the statistical analysis, the association was not statistically significant despite an odds ratio of 1.44 (95% confidence interval, 0.911-2.27; P = .119).

“Births in the 12 hospitals studied appear to have been organized to take place more frequently on the working weekday rather than weekend days,” wrote Dr. Restrepo and her colleagues in the poster accompanying the presentation. Although the study wasn’t designed to answer this particular question, Dr. Restrepo said in discussion during the poster session that planned deliveries, such as inductions and cesarean deliveries, are likely to happen during the week, while the case mix is wider on weekends. Patient characteristics, as well as staffing patterns, may come into play.

The researchers also asked whether birth volume at a given institution increases the odds of neonatal death on weekends. Here, they found a significant inverse relationship between hospital birth volume and neonatal deaths (r = –0.021; P less than .001). With each additional increase of 1% in the weekday birth rate, the odds of neonatal death dropped by approximately 7.4%.

Examining the Tarrant County data further, Dr. Restrepo and her colleagues found that the hospitals with higher birth volumes had a more even distribution of births across the days of the week, with resulting lower concentrations of births during the week (r = –.394; P less than .001).

[email protected]

SOURCE: Restrepo E et al. ACOG 2018, Abstract 22R.

ORLANDO – When is it rational to consider de-escalating, or even stopping, antibiotics for septic patients, and how will patients’ future health be affected by antibiotic use during critical illnesses?

According to Jennifer Hanrahan, DO, of Case Western Reserve University, Cleveland, locating the tipping point between optimal care for the individual patient in sepsis, and the importance of antibiotic stewardship is a balancing act. It’s a process guided by laboratory findings, by knowledge of local pathogens and patterns of antimicrobial resistance, and also by clinical judgment, she said at the annual meeting of the Society of Hospital Medicine.

By all means, begin antibiotics for patients with sepsis, Dr. Hanrahan, also medical director of infection prevention at MetroHealth Medical Center, Cleveland, told attendees at a pre-course at HM18. “Prompt initiation of antibiotics for sepsis is critical, and appropriate use of antibiotics decreases mortality.” However, she noted, de-escalation of antibiotics also decreases mortality.

“What is antibiotic stewardship? Most of us think of this as the microbial stewardship police calling to ask you, ‘Why are you using this antibiotic?’’ she said. “It’s really the right antibiotic, for the right diagnosis, for the appropriate duration.”

Of course, Dr. Hanrahan said, any medication is associated with potential adverse events, and antibiotics are no different. “Almost one-third of antibiotics given are either unnecessary or inappropriate,” she said.

Antimicrobial resistance is a very serious public health threat, Dr. Hanrahan affirmed. “Antibiotic use is the most important modifiable factor related to development of antibiotic resistance. With regard to multidrug resistant [MDR] gram negatives, we are running out of antibiotics” to treat these organisms, she said, noting that “Many antibiotics to treat MDRs are “astronomically expensive – and that’s a really big problem.”

It’s important to remember that, when antibiotics are prescribed, “You’re affecting the microbiome not just of that patient, but of those around them,” as resistance factors are potentially spread from one individual’s microbiome to their friends, family, and other contacts, Dr. Hanrahan said.

The later risk of sepsis has also shown to be elevated for individuals who have received high-risk antibiotics such as fluoroquinolones, third- and fourth-generation cephalosporins, beta-lactamase inhibitor formulations, vancomycin, and carbapenems – many of which are also used to treat sepsis. All of these antibiotics kill anaerobic bacteria, Dr. Hanrahan said, and “when you kill anaerobes you do a lot of bad things to people.”
 

Identifying the pathogens

There are already many frightening players in the antibiotic-resistant landscape. Among them are carbapenem-resistant Enterobacteriaceae, increasingly common in health care settings. Unfortunately, with methicillin-resistant Staphylococcus aureus (MRSA), “we’ve lost the battle,” Dr. Hanrahan said.

Acinetobacter is another increasing threat, she said, as is Candida auris, which has caused large outbreaks in Europe. Because it’s resistant to azole antifungals, once C. auris comes to U.S. hospitals, “You’re going to have a really big problem,” she said. Finally, multidrug resistant and extremely drug resistant Pseudomonas species are being encountered with increasing frequency.

And, of course, Clostridium difficile infections continue to ravage older populations. “One in 11 people aged 65 or older will die from C. diff infections,” said Dr. Hanrahan.

For all of these bacteria, she said, “I can’t tell you what antibiotics to use because you have to know what the organisms are in your hospital.” A good resource for tracking local resistance patterns is the information provided by the Centers for Disease Control and Prevention, including interactive maps showing health care–associated infections, as well as HealthMap ResistanceOpen, which maps antibiotic resistance alerts across the United States. The CDC also offers training on antibiotic stewardship; Dr. Hanrahan said the several hours she spent completing the training were well spent.

After a broad-spectrum antibiotic is initiated for sepsis, Dr. Hanrahan said that the next infectious disease–related steps should focus on identifying pathogens so antimicrobial therapy can be tailored or scaled back appropriately. In many cases, this will mean obtaining blood cultures – ideally, two sets from two separate sites. It’s no longer thought necessary to separate the blood draws by 20 minutes, or to try to time the draw during a febrile episode, she said.

What is important is to make sure that you’re not treating contamination or colonization – “Treat only clinically significant infections,” Dr. Hanrahan said. A common red herring, especially among elderly individuals coming from assisted living or in patients with indwelling urinary catheters, is a positive urine culture in the absence of signs or symptoms of urinary tract infection. Think twice about whether this truly represents a source of infection, she said. “Don’t treat asymptomatic bacteriuria.”

In order to avoid “chasing contamination,” do not obtain the blood culture samples from a venipuncture site. “Contamination is twice as likely when drawing from a venipuncture site,” Dr. Hanrahan noted. “When possible you should avoid this.”

It’s also important to remember that 10% of fever in hospitalized individuals is from a noninfectious source. “Take a careful history, and do a physical exam to help distinguish infections from other causes of fever,” said Dr. Hanrahan.

Additional investigations to consider in highly immunocompromised patients might include both mycobacterial and fungal cultures, although these studies are otherwise generally low yield. And, she said, “Don’t send catheter-tip cultures – it’s pointless, and it really doesn’t add much information.”

Good clinical judgment still goes a long way toward guiding therapy. “If a patient is stable and it’s not clear whether an antibiotic is needed, consider waiting and re-evaluating later,” Dr. Hanrahan said.

Generally, duration of treatment should also be clinically based. “Stop antibiotics as soon as possible, and remove catheters as soon as possible,” Dr. Hanrahan said, adding that few infections really warrant treatment for a fixed amount of time. These include meningitis, endocarditis, tuberculosis, and many cases of osteomyelitis.

Similarly, when a patient who had been ill now looks well, feels well, and is stable or improving, there’s usually no need for repeat blood cultures, Dr. Hanrahan said. Still, a cautious balance is where most clinicians will wind up.

“I learned a long time ago that I have to do the things that let me go home and sleep at night,” she concluded.

Dr. Hanrahan reported having been a consultant for Gilead, Astellas, and Cempra.

ORLANDO – When is it rational to consider de-escalating, or even stopping, antibiotics for septic patients, and how will patients’ future health be affected by antibiotic use during critical illnesses?

According to Jennifer Hanrahan, DO, of Case Western Reserve University, Cleveland, locating the tipping point between optimal care for the individual patient in sepsis, and the importance of antibiotic stewardship is a balancing act. It’s a process guided by laboratory findings, by knowledge of local pathogens and patterns of antimicrobial resistance, and also by clinical judgment, she said at the annual meeting of the Society of Hospital Medicine.

By all means, begin antibiotics for patients with sepsis, Dr. Hanrahan, also medical director of infection prevention at MetroHealth Medical Center, Cleveland, told attendees at a pre-course at HM18. “Prompt initiation of antibiotics for sepsis is critical, and appropriate use of antibiotics decreases mortality.” However, she noted, de-escalation of antibiotics also decreases mortality.

“What is antibiotic stewardship? Most of us think of this as the microbial stewardship police calling to ask you, ‘Why are you using this antibiotic?’’ she said. “It’s really the right antibiotic, for the right diagnosis, for the appropriate duration.”

Of course, Dr. Hanrahan said, any medication is associated with potential adverse events, and antibiotics are no different. “Almost one-third of antibiotics given are either unnecessary or inappropriate,” she said.

Antimicrobial resistance is a very serious public health threat, Dr. Hanrahan affirmed. “Antibiotic use is the most important modifiable factor related to development of antibiotic resistance. With regard to multidrug resistant [MDR] gram negatives, we are running out of antibiotics” to treat these organisms, she said, noting that “Many antibiotics to treat MDRs are “astronomically expensive – and that’s a really big problem.”

It’s important to remember that, when antibiotics are prescribed, “You’re affecting the microbiome not just of that patient, but of those around them,” as resistance factors are potentially spread from one individual’s microbiome to their friends, family, and other contacts, Dr. Hanrahan said.

The later risk of sepsis has also shown to be elevated for individuals who have received high-risk antibiotics such as fluoroquinolones, third- and fourth-generation cephalosporins, beta-lactamase inhibitor formulations, vancomycin, and carbapenems – many of which are also used to treat sepsis. All of these antibiotics kill anaerobic bacteria, Dr. Hanrahan said, and “when you kill anaerobes you do a lot of bad things to people.”
 

Identifying the pathogens

There are already many frightening players in the antibiotic-resistant landscape. Among them are carbapenem-resistant Enterobacteriaceae, increasingly common in health care settings. Unfortunately, with methicillin-resistant Staphylococcus aureus (MRSA), “we’ve lost the battle,” Dr. Hanrahan said.

Acinetobacter is another increasing threat, she said, as is Candida auris, which has caused large outbreaks in Europe. Because it’s resistant to azole antifungals, once C. auris comes to U.S. hospitals, “You’re going to have a really big problem,” she said. Finally, multidrug resistant and extremely drug resistant Pseudomonas species are being encountered with increasing frequency.

And, of course, Clostridium difficile infections continue to ravage older populations. “One in 11 people aged 65 or older will die from C. diff infections,” said Dr. Hanrahan.

For all of these bacteria, she said, “I can’t tell you what antibiotics to use because you have to know what the organisms are in your hospital.” A good resource for tracking local resistance patterns is the information provided by the Centers for Disease Control and Prevention, including interactive maps showing health care–associated infections, as well as HealthMap ResistanceOpen, which maps antibiotic resistance alerts across the United States. The CDC also offers training on antibiotic stewardship; Dr. Hanrahan said the several hours she spent completing the training were well spent.

After a broad-spectrum antibiotic is initiated for sepsis, Dr. Hanrahan said that the next infectious disease–related steps should focus on identifying pathogens so antimicrobial therapy can be tailored or scaled back appropriately. In many cases, this will mean obtaining blood cultures – ideally, two sets from two separate sites. It’s no longer thought necessary to separate the blood draws by 20 minutes, or to try to time the draw during a febrile episode, she said.

What is important is to make sure that you’re not treating contamination or colonization – “Treat only clinically significant infections,” Dr. Hanrahan said. A common red herring, especially among elderly individuals coming from assisted living or in patients with indwelling urinary catheters, is a positive urine culture in the absence of signs or symptoms of urinary tract infection. Think twice about whether this truly represents a source of infection, she said. “Don’t treat asymptomatic bacteriuria.”

In order to avoid “chasing contamination,” do not obtain the blood culture samples from a venipuncture site. “Contamination is twice as likely when drawing from a venipuncture site,” Dr. Hanrahan noted. “When possible you should avoid this.”

It’s also important to remember that 10% of fever in hospitalized individuals is from a noninfectious source. “Take a careful history, and do a physical exam to help distinguish infections from other causes of fever,” said Dr. Hanrahan.

Additional investigations to consider in highly immunocompromised patients might include both mycobacterial and fungal cultures, although these studies are otherwise generally low yield. And, she said, “Don’t send catheter-tip cultures – it’s pointless, and it really doesn’t add much information.”

Good clinical judgment still goes a long way toward guiding therapy. “If a patient is stable and it’s not clear whether an antibiotic is needed, consider waiting and re-evaluating later,” Dr. Hanrahan said.

Generally, duration of treatment should also be clinically based. “Stop antibiotics as soon as possible, and remove catheters as soon as possible,” Dr. Hanrahan said, adding that few infections really warrant treatment for a fixed amount of time. These include meningitis, endocarditis, tuberculosis, and many cases of osteomyelitis.

Similarly, when a patient who had been ill now looks well, feels well, and is stable or improving, there’s usually no need for repeat blood cultures, Dr. Hanrahan said. Still, a cautious balance is where most clinicians will wind up.

“I learned a long time ago that I have to do the things that let me go home and sleep at night,” she concluded.

Dr. Hanrahan reported having been a consultant for Gilead, Astellas, and Cempra.

ORLANDO – When is it rational to consider de-escalating, or even stopping, antibiotics for septic patients, and how will patients’ future health be affected by antibiotic use during critical illnesses?

According to Jennifer Hanrahan, DO, of Case Western Reserve University, Cleveland, locating the tipping point between optimal care for the individual patient in sepsis, and the importance of antibiotic stewardship is a balancing act. It’s a process guided by laboratory findings, by knowledge of local pathogens and patterns of antimicrobial resistance, and also by clinical judgment, she said at the annual meeting of the Society of Hospital Medicine.

By all means, begin antibiotics for patients with sepsis, Dr. Hanrahan, also medical director of infection prevention at MetroHealth Medical Center, Cleveland, told attendees at a pre-course at HM18. “Prompt initiation of antibiotics for sepsis is critical, and appropriate use of antibiotics decreases mortality.” However, she noted, de-escalation of antibiotics also decreases mortality.

“What is antibiotic stewardship? Most of us think of this as the microbial stewardship police calling to ask you, ‘Why are you using this antibiotic?’’ she said. “It’s really the right antibiotic, for the right diagnosis, for the appropriate duration.”

Of course, Dr. Hanrahan said, any medication is associated with potential adverse events, and antibiotics are no different. “Almost one-third of antibiotics given are either unnecessary or inappropriate,” she said.

Antimicrobial resistance is a very serious public health threat, Dr. Hanrahan affirmed. “Antibiotic use is the most important modifiable factor related to development of antibiotic resistance. With regard to multidrug resistant [MDR] gram negatives, we are running out of antibiotics” to treat these organisms, she said, noting that “Many antibiotics to treat MDRs are “astronomically expensive – and that’s a really big problem.”

It’s important to remember that, when antibiotics are prescribed, “You’re affecting the microbiome not just of that patient, but of those around them,” as resistance factors are potentially spread from one individual’s microbiome to their friends, family, and other contacts, Dr. Hanrahan said.

The later risk of sepsis has also shown to be elevated for individuals who have received high-risk antibiotics such as fluoroquinolones, third- and fourth-generation cephalosporins, beta-lactamase inhibitor formulations, vancomycin, and carbapenems – many of which are also used to treat sepsis. All of these antibiotics kill anaerobic bacteria, Dr. Hanrahan said, and “when you kill anaerobes you do a lot of bad things to people.”
 

Identifying the pathogens

There are already many frightening players in the antibiotic-resistant landscape. Among them are carbapenem-resistant Enterobacteriaceae, increasingly common in health care settings. Unfortunately, with methicillin-resistant Staphylococcus aureus (MRSA), “we’ve lost the battle,” Dr. Hanrahan said.

Acinetobacter is another increasing threat, she said, as is Candida auris, which has caused large outbreaks in Europe. Because it’s resistant to azole antifungals, once C. auris comes to U.S. hospitals, “You’re going to have a really big problem,” she said. Finally, multidrug resistant and extremely drug resistant Pseudomonas species are being encountered with increasing frequency.

And, of course, Clostridium difficile infections continue to ravage older populations. “One in 11 people aged 65 or older will die from C. diff infections,” said Dr. Hanrahan.

For all of these bacteria, she said, “I can’t tell you what antibiotics to use because you have to know what the organisms are in your hospital.” A good resource for tracking local resistance patterns is the information provided by the Centers for Disease Control and Prevention, including interactive maps showing health care–associated infections, as well as HealthMap ResistanceOpen, which maps antibiotic resistance alerts across the United States. The CDC also offers training on antibiotic stewardship; Dr. Hanrahan said the several hours she spent completing the training were well spent.

After a broad-spectrum antibiotic is initiated for sepsis, Dr. Hanrahan said that the next infectious disease–related steps should focus on identifying pathogens so antimicrobial therapy can be tailored or scaled back appropriately. In many cases, this will mean obtaining blood cultures – ideally, two sets from two separate sites. It’s no longer thought necessary to separate the blood draws by 20 minutes, or to try to time the draw during a febrile episode, she said.

What is important is to make sure that you’re not treating contamination or colonization – “Treat only clinically significant infections,” Dr. Hanrahan said. A common red herring, especially among elderly individuals coming from assisted living or in patients with indwelling urinary catheters, is a positive urine culture in the absence of signs or symptoms of urinary tract infection. Think twice about whether this truly represents a source of infection, she said. “Don’t treat asymptomatic bacteriuria.”

In order to avoid “chasing contamination,” do not obtain the blood culture samples from a venipuncture site. “Contamination is twice as likely when drawing from a venipuncture site,” Dr. Hanrahan noted. “When possible you should avoid this.”

It’s also important to remember that 10% of fever in hospitalized individuals is from a noninfectious source. “Take a careful history, and do a physical exam to help distinguish infections from other causes of fever,” said Dr. Hanrahan.

Additional investigations to consider in highly immunocompromised patients might include both mycobacterial and fungal cultures, although these studies are otherwise generally low yield. And, she said, “Don’t send catheter-tip cultures – it’s pointless, and it really doesn’t add much information.”

Good clinical judgment still goes a long way toward guiding therapy. “If a patient is stable and it’s not clear whether an antibiotic is needed, consider waiting and re-evaluating later,” Dr. Hanrahan said.

Generally, duration of treatment should also be clinically based. “Stop antibiotics as soon as possible, and remove catheters as soon as possible,” Dr. Hanrahan said, adding that few infections really warrant treatment for a fixed amount of time. These include meningitis, endocarditis, tuberculosis, and many cases of osteomyelitis.

Similarly, when a patient who had been ill now looks well, feels well, and is stable or improving, there’s usually no need for repeat blood cultures, Dr. Hanrahan said. Still, a cautious balance is where most clinicians will wind up.

“I learned a long time ago that I have to do the things that let me go home and sleep at night,” she concluded.

Dr. Hanrahan reported having been a consultant for Gilead, Astellas, and Cempra.

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

[email protected]

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

[email protected]

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

[email protected]

BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.

However, clinicians should be alert for the greater potential for gastrointestinal upset in older patients with higher doses of GLP-1 receptor agonists, said the study’s first author, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.

The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.

Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).

“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.

Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.

The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.

[email protected]

SOURCE: Aroda V et al. AACE 2018. Abstract 245.

BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.

However, clinicians should be alert for the greater potential for gastrointestinal upset in older patients with higher doses of GLP-1 receptor agonists, said the study’s first author, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.

The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.

Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).

“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.

Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.

The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.

[email protected]

SOURCE: Aroda V et al. AACE 2018. Abstract 245.

BOSTON – Efficacy and safety of two glucagonlike peptide 1 (GLP-1) receptor agonists in type 2 diabetes mellitus were similar between older and younger adults, according to a post hoc analysis of the SUSTAIN 7 clinical trial data.

However, clinicians should be alert for the greater potential for gastrointestinal upset in older patients with higher doses of GLP-1 receptor agonists, said the study’s first author, Vanita Aroda, MD, associate director for clinical diabetes research at Brigham and Women’s Hospital, Boston.

The SUSTAIN 7 trial compared low-dose semaglutide (0.5 mg) with low-dose dulaglutide (0.75 mg), and high-dose semaglutide (1.0 mg) with high-dose dulaglutide (1.5 mg) as add-on therapy to metformin for adults with type 2 diabetes. All medications were given as once-weekly subcutaneous injections.

Dr. Aroda and her collaborators performed a subgroup analysis of the SUSTAIN 7 data that compared 260 patients aged 65 years and older (mean, 69.3 years) with 939 patients younger than 65 years (mean, 51.9 years).

“What we found is that the efficacy results … were similar to what we saw in the general population. We did not lose the efficacy in the older adult population,” said Dr. Aroda in an interview at the annual meeting of the American Association for Clinical Endocrinology.

Weight loss was similar in older and younger patients, though there was “maybe a tiny bit more in the older adults,” said Dr. Aroda: Older participants had a 4.4-kg reduction in weight, compared with 4.9-kg reduction in the younger population, on low-dose semaglutide. For low-dose dulaglutide, losses were an average 2.6 kg in the elderly versus 2.2 kg in the younger participants.

The higher doses of each resulted in greater weight loss, up to a mean 6.7 kg in elderly participants on high-dose semaglutide, with the same marginally greater losses seen in older participants.

[email protected]

SOURCE: Aroda V et al. AACE 2018. Abstract 245.

BOSTON – Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

[email protected]

SOURCE: Weaver K et al. AACE 2018, Abstract 210.

BOSTON – Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

[email protected]

SOURCE: Weaver K et al. AACE 2018, Abstract 210.

BOSTON – Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

[email protected]

SOURCE: Weaver K et al. AACE 2018, Abstract 210.