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What do you call a koala who is too sweet for its own good? Diabetic
SAN DIEGO – The 14-pound patient with the deep-pile complexion was lethargic, kept drinking a lot of water, and had a glucose level in the range of 600-700 mg/dL. He was nearly comatose by the time medical staff transferred him to a specialized facility.
The diagnosis: Diabetes. The treatment: Insulin. But multiple daily skin pricks were quite a challenge for Quincy the koala. After all, he requires up to 22 hours of shut-eye each day.
What to do? The veterinary staff at the San Diego Zoo turned to the experts – an endocrinologist and a manufacturer of continuous glucose monitors. Now, Quincy has his own CGM, and a medical team that is tracking his glucose levels in real time on their smartphones.
In fact, Athena Philis-Tsimikas, MD, of the Scripps Whittier Diabetes Institute, pulls out her phone and checks on him at least a couple times a day. She also gets alerts if his blood sugar drops too quickly.
“He is definitely another one of my patients,” she said in an interview. But he’s the only one who lives in trees and enjoys a nice eucalyptus smoothie.
Humans are hardly the only mammals who get diabetes
Veterinarians are quite familiar with diabetes. A wide variety of mammals from pigs and apes to horses and dolphins can develop an equivalent of the human condition. Dogs may be prescribed daily insulin shots, and cats even develop peripheral neuropathy and retinopathy like humans with diabetes.
So it’s not entirely surprising that a team at the Los Angeles Zoo diagnosed Quincy, a 3-year-old Queensland koala, with diabetes.
Quincy’s glucose levels should have been around 80-130 mg/dL, similar to the ideal levels in humans, said San Diego Zoo senior veterinarian Cora Singleton, DVM, in an interview. But tests prompted by his symptoms showed his levels were high, she said, and they stayed that way. According to her, that suggested he wasn’t just having a one-time elevation that animals can experience when they’re stressed.
Unfortunately, there are only a few scattered reports of diabetes in koalas, and “there’s not anything documented about treating a koala over a long term,” Dr. Singleton said. “We’re in uncharted territory here.”
So the Los Angeles Zoo sent Quincy down the California coast for more specialized treatment. The San Diego Zoo’s veterinary staff took in Quincy and treated him with glucose tests and insulin shots, Dr. Singleton said. “But we were looking a way for to get more information with less disturbance to Quincy.”
Someone mentioned the idea of a sensor. “We thought, ‘What a great idea,’” Dr. Singleton said. “It would be a way for us to get a lot of information and find out how his highs and lows are related.”
That’s when the team turned to local endocrinologist Dr. Tsimikas for a helping hand.
The key to koala calming: Eucalyptus smoothies
“They did reach out to us and asked what kind of sensors might be available. We connected them to Dexcom,” a CGM company that’s based in San Diego, Dr. Tsimikas said. “We knew the newest one was coming along and suggested they place that on him as a starting point.”
On June 1, a zoo team attached a Dexcom G6 Continuous Glucose Monitoring System to the koala’s side.
“He’s doing very well. He tolerates the CGM superbly,” Dr. Singleton said. And Quincy doesn’t react when sensors are applied, she said, although it helps that he gets to enjoy a eucalyptus smoothie during the procedure. “Put that in a big syringe, and he’ll volunteer for most anything,” she said.
Obesity can trigger diabetes in mammals other than humans. Could eucalyptus overindulgence explain Quincy’s case of diabetes? Nope.
According to Dr. Tsimikas, the ingredients of the eucalyptus smoothie are just pureed eucalyptus leaves that “go down fast and easy.” These naturally have a nice mix of carbohydrates, fat, and protein to better manage the koala’s sugars and other nutritional needs. If he is dropping his blood sugar values fast, there is another dextrose drink they give him in small amounts, which contains 5-10 g carbohydrates. This is enough to help bring his glucose values back up. It is similar to the treatment recommendations provided to humans with diabetes where they are told to take 15 g of carbohydrates such as honey, hard candies, or juice to prevent a severe hypoglycemic episode.
Dr. Singleton noted that Quincy appears to have the koala equivalent is type 1 diabetes mellitus (T1DM).
Dr. Tsimikas noted “We are not finding the typical antibodies that we find in human T1DM. Quincy is showing low insulin levels, which is why it more closely resembles T1DM. We will be doing further analysis and comparisons with nondiabetic koalas in the future to see if it can be better differentiated.
While he appears to have type 1 diabetes, it’s not clear why he developed it, Dr. Singleton said.
While Quincy is only 3 years old, he’s a full-fledged adult in koala terms. Koalas typically live up to their mid-teens, she said.
This speechless patient still manages to communicate
The San Diego Zoo’s veterinary staff is monitoring Quincy and trying to understand how his glucose levels and daily insulin shots affect him. His tiny size has ruled out use of an insulin pump: Although the insulin pumps have been getting smaller and lighter, they are still too large to attach to our tiny friend. Especially since he would need both the CGM device and the pump, there is not a lot of surface area on his body for attachment of all the devices, according to Dr. Tsimikas.
Since Quincy is so tiny, insulin doses must be minuscule to avoid sending him into hypoglycemia, Dr. Tsimikas said. She said the koala’s medical team is planning to try using a NovoPen Echo injector with a half-unit of insulin.
Dr. Singleton noted that for now, “he’s maintaining his body weight, and he has days when he feels spunky. Sometimes, when he knows it’s breakfast time, and he hears his caretakers coming up the doorway with his breakfast, he’ll be very active on his perch.”
But he has sluggish days, too, when he’ll try to sleep in. Dr. Singleton keeps an eye out for grogginess and signs of weakness and hypoglycemia or hyperglycemia like “a little wobble in his step.”
“The biggest thing I’ve learned from Quincy is the value of his particular nonverbal cues,” she said. “I’m starting to understand when he feels like his sugars are a little high or a little low. I imagine that doctors and parents have the same challenges with little patients, along with figuring out how you communicate that this is supposed to help them.”
Dr. Tsimikas agreed, noting that she sees similarities between Quincy and patients who are hospitalized and can’t easily communicate. Now, “we can track the folks who are on the CGM and intervene earlier than before,” said Dr. Tsimikas, who’s part of a clinical trial team testing CGM devices in two hospitals. “It’s almost like having another vital sign.
“It is only when we have all the data on all the other factors that can influence blood sugar, such as eating patterns, insulin dose and timing, and activity level that we can more accurately adjust the medical interventions.” This requires collaboration between all the groups involved in Quincy’s care. In koalas, the collaboration is with the veterinarian, koala zookeepers, dietitian, and the technology monitoring team. Whereas, for humans, we need parents, care providers, diabetes educators, dietitians, and physicians.
It’s not clear if Quincy will need his CGM for the rest of his life. If he’s stable on a specific insulin dose, Dr. Tsimikas said, he may not need it. But it sounds like eucalyptus smoothies will always be a vital part of his regimen.
In the name of thoroughness, take note that Quincy is not the first diabetic zoo animal whose care involved physicians from Scripps. “We have had several other consultations for animals with diabetes. Nearly 25 years ago, a roller-skating chimpanzee with diabetes was brought to the Scripps Whittier Institute labs for evaluation and treatment recommendations. A few years later, one of our medical directors, Alberto Hayek, MD, advised on the care of Lune, a diabetic baboon at the San Diego Zoo, for insulin management. This time we are making house calls to the zoo to treat Quincy in his home environment. Each animal experience offers opportunities to expand our knowledge about diabetes care and exchange approaches that we might not otherwise be aware of. This has been fun and rewarding. I am looking forward to seeing further outcomes from our interactions with Quincy,” according to Dr. Tsimikas.
Dr. Tsimikas reports that her center conducts research with Dexcom and Novo Nordisk. Dr. Singleton reports no relevant disclosures.
SAN DIEGO – The 14-pound patient with the deep-pile complexion was lethargic, kept drinking a lot of water, and had a glucose level in the range of 600-700 mg/dL. He was nearly comatose by the time medical staff transferred him to a specialized facility.
The diagnosis: Diabetes. The treatment: Insulin. But multiple daily skin pricks were quite a challenge for Quincy the koala. After all, he requires up to 22 hours of shut-eye each day.
What to do? The veterinary staff at the San Diego Zoo turned to the experts – an endocrinologist and a manufacturer of continuous glucose monitors. Now, Quincy has his own CGM, and a medical team that is tracking his glucose levels in real time on their smartphones.
In fact, Athena Philis-Tsimikas, MD, of the Scripps Whittier Diabetes Institute, pulls out her phone and checks on him at least a couple times a day. She also gets alerts if his blood sugar drops too quickly.
“He is definitely another one of my patients,” she said in an interview. But he’s the only one who lives in trees and enjoys a nice eucalyptus smoothie.
Humans are hardly the only mammals who get diabetes
Veterinarians are quite familiar with diabetes. A wide variety of mammals from pigs and apes to horses and dolphins can develop an equivalent of the human condition. Dogs may be prescribed daily insulin shots, and cats even develop peripheral neuropathy and retinopathy like humans with diabetes.
So it’s not entirely surprising that a team at the Los Angeles Zoo diagnosed Quincy, a 3-year-old Queensland koala, with diabetes.
Quincy’s glucose levels should have been around 80-130 mg/dL, similar to the ideal levels in humans, said San Diego Zoo senior veterinarian Cora Singleton, DVM, in an interview. But tests prompted by his symptoms showed his levels were high, she said, and they stayed that way. According to her, that suggested he wasn’t just having a one-time elevation that animals can experience when they’re stressed.
Unfortunately, there are only a few scattered reports of diabetes in koalas, and “there’s not anything documented about treating a koala over a long term,” Dr. Singleton said. “We’re in uncharted territory here.”
So the Los Angeles Zoo sent Quincy down the California coast for more specialized treatment. The San Diego Zoo’s veterinary staff took in Quincy and treated him with glucose tests and insulin shots, Dr. Singleton said. “But we were looking a way for to get more information with less disturbance to Quincy.”
Someone mentioned the idea of a sensor. “We thought, ‘What a great idea,’” Dr. Singleton said. “It would be a way for us to get a lot of information and find out how his highs and lows are related.”
That’s when the team turned to local endocrinologist Dr. Tsimikas for a helping hand.
The key to koala calming: Eucalyptus smoothies
“They did reach out to us and asked what kind of sensors might be available. We connected them to Dexcom,” a CGM company that’s based in San Diego, Dr. Tsimikas said. “We knew the newest one was coming along and suggested they place that on him as a starting point.”
On June 1, a zoo team attached a Dexcom G6 Continuous Glucose Monitoring System to the koala’s side.
“He’s doing very well. He tolerates the CGM superbly,” Dr. Singleton said. And Quincy doesn’t react when sensors are applied, she said, although it helps that he gets to enjoy a eucalyptus smoothie during the procedure. “Put that in a big syringe, and he’ll volunteer for most anything,” she said.
Obesity can trigger diabetes in mammals other than humans. Could eucalyptus overindulgence explain Quincy’s case of diabetes? Nope.
According to Dr. Tsimikas, the ingredients of the eucalyptus smoothie are just pureed eucalyptus leaves that “go down fast and easy.” These naturally have a nice mix of carbohydrates, fat, and protein to better manage the koala’s sugars and other nutritional needs. If he is dropping his blood sugar values fast, there is another dextrose drink they give him in small amounts, which contains 5-10 g carbohydrates. This is enough to help bring his glucose values back up. It is similar to the treatment recommendations provided to humans with diabetes where they are told to take 15 g of carbohydrates such as honey, hard candies, or juice to prevent a severe hypoglycemic episode.
Dr. Singleton noted that Quincy appears to have the koala equivalent is type 1 diabetes mellitus (T1DM).
Dr. Tsimikas noted “We are not finding the typical antibodies that we find in human T1DM. Quincy is showing low insulin levels, which is why it more closely resembles T1DM. We will be doing further analysis and comparisons with nondiabetic koalas in the future to see if it can be better differentiated.
While he appears to have type 1 diabetes, it’s not clear why he developed it, Dr. Singleton said.
While Quincy is only 3 years old, he’s a full-fledged adult in koala terms. Koalas typically live up to their mid-teens, she said.
This speechless patient still manages to communicate
The San Diego Zoo’s veterinary staff is monitoring Quincy and trying to understand how his glucose levels and daily insulin shots affect him. His tiny size has ruled out use of an insulin pump: Although the insulin pumps have been getting smaller and lighter, they are still too large to attach to our tiny friend. Especially since he would need both the CGM device and the pump, there is not a lot of surface area on his body for attachment of all the devices, according to Dr. Tsimikas.
Since Quincy is so tiny, insulin doses must be minuscule to avoid sending him into hypoglycemia, Dr. Tsimikas said. She said the koala’s medical team is planning to try using a NovoPen Echo injector with a half-unit of insulin.
Dr. Singleton noted that for now, “he’s maintaining his body weight, and he has days when he feels spunky. Sometimes, when he knows it’s breakfast time, and he hears his caretakers coming up the doorway with his breakfast, he’ll be very active on his perch.”
But he has sluggish days, too, when he’ll try to sleep in. Dr. Singleton keeps an eye out for grogginess and signs of weakness and hypoglycemia or hyperglycemia like “a little wobble in his step.”
“The biggest thing I’ve learned from Quincy is the value of his particular nonverbal cues,” she said. “I’m starting to understand when he feels like his sugars are a little high or a little low. I imagine that doctors and parents have the same challenges with little patients, along with figuring out how you communicate that this is supposed to help them.”
Dr. Tsimikas agreed, noting that she sees similarities between Quincy and patients who are hospitalized and can’t easily communicate. Now, “we can track the folks who are on the CGM and intervene earlier than before,” said Dr. Tsimikas, who’s part of a clinical trial team testing CGM devices in two hospitals. “It’s almost like having another vital sign.
“It is only when we have all the data on all the other factors that can influence blood sugar, such as eating patterns, insulin dose and timing, and activity level that we can more accurately adjust the medical interventions.” This requires collaboration between all the groups involved in Quincy’s care. In koalas, the collaboration is with the veterinarian, koala zookeepers, dietitian, and the technology monitoring team. Whereas, for humans, we need parents, care providers, diabetes educators, dietitians, and physicians.
It’s not clear if Quincy will need his CGM for the rest of his life. If he’s stable on a specific insulin dose, Dr. Tsimikas said, he may not need it. But it sounds like eucalyptus smoothies will always be a vital part of his regimen.
In the name of thoroughness, take note that Quincy is not the first diabetic zoo animal whose care involved physicians from Scripps. “We have had several other consultations for animals with diabetes. Nearly 25 years ago, a roller-skating chimpanzee with diabetes was brought to the Scripps Whittier Institute labs for evaluation and treatment recommendations. A few years later, one of our medical directors, Alberto Hayek, MD, advised on the care of Lune, a diabetic baboon at the San Diego Zoo, for insulin management. This time we are making house calls to the zoo to treat Quincy in his home environment. Each animal experience offers opportunities to expand our knowledge about diabetes care and exchange approaches that we might not otherwise be aware of. This has been fun and rewarding. I am looking forward to seeing further outcomes from our interactions with Quincy,” according to Dr. Tsimikas.
Dr. Tsimikas reports that her center conducts research with Dexcom and Novo Nordisk. Dr. Singleton reports no relevant disclosures.
SAN DIEGO – The 14-pound patient with the deep-pile complexion was lethargic, kept drinking a lot of water, and had a glucose level in the range of 600-700 mg/dL. He was nearly comatose by the time medical staff transferred him to a specialized facility.
The diagnosis: Diabetes. The treatment: Insulin. But multiple daily skin pricks were quite a challenge for Quincy the koala. After all, he requires up to 22 hours of shut-eye each day.
What to do? The veterinary staff at the San Diego Zoo turned to the experts – an endocrinologist and a manufacturer of continuous glucose monitors. Now, Quincy has his own CGM, and a medical team that is tracking his glucose levels in real time on their smartphones.
In fact, Athena Philis-Tsimikas, MD, of the Scripps Whittier Diabetes Institute, pulls out her phone and checks on him at least a couple times a day. She also gets alerts if his blood sugar drops too quickly.
“He is definitely another one of my patients,” she said in an interview. But he’s the only one who lives in trees and enjoys a nice eucalyptus smoothie.
Humans are hardly the only mammals who get diabetes
Veterinarians are quite familiar with diabetes. A wide variety of mammals from pigs and apes to horses and dolphins can develop an equivalent of the human condition. Dogs may be prescribed daily insulin shots, and cats even develop peripheral neuropathy and retinopathy like humans with diabetes.
So it’s not entirely surprising that a team at the Los Angeles Zoo diagnosed Quincy, a 3-year-old Queensland koala, with diabetes.
Quincy’s glucose levels should have been around 80-130 mg/dL, similar to the ideal levels in humans, said San Diego Zoo senior veterinarian Cora Singleton, DVM, in an interview. But tests prompted by his symptoms showed his levels were high, she said, and they stayed that way. According to her, that suggested he wasn’t just having a one-time elevation that animals can experience when they’re stressed.
Unfortunately, there are only a few scattered reports of diabetes in koalas, and “there’s not anything documented about treating a koala over a long term,” Dr. Singleton said. “We’re in uncharted territory here.”
So the Los Angeles Zoo sent Quincy down the California coast for more specialized treatment. The San Diego Zoo’s veterinary staff took in Quincy and treated him with glucose tests and insulin shots, Dr. Singleton said. “But we were looking a way for to get more information with less disturbance to Quincy.”
Someone mentioned the idea of a sensor. “We thought, ‘What a great idea,’” Dr. Singleton said. “It would be a way for us to get a lot of information and find out how his highs and lows are related.”
That’s when the team turned to local endocrinologist Dr. Tsimikas for a helping hand.
The key to koala calming: Eucalyptus smoothies
“They did reach out to us and asked what kind of sensors might be available. We connected them to Dexcom,” a CGM company that’s based in San Diego, Dr. Tsimikas said. “We knew the newest one was coming along and suggested they place that on him as a starting point.”
On June 1, a zoo team attached a Dexcom G6 Continuous Glucose Monitoring System to the koala’s side.
“He’s doing very well. He tolerates the CGM superbly,” Dr. Singleton said. And Quincy doesn’t react when sensors are applied, she said, although it helps that he gets to enjoy a eucalyptus smoothie during the procedure. “Put that in a big syringe, and he’ll volunteer for most anything,” she said.
Obesity can trigger diabetes in mammals other than humans. Could eucalyptus overindulgence explain Quincy’s case of diabetes? Nope.
According to Dr. Tsimikas, the ingredients of the eucalyptus smoothie are just pureed eucalyptus leaves that “go down fast and easy.” These naturally have a nice mix of carbohydrates, fat, and protein to better manage the koala’s sugars and other nutritional needs. If he is dropping his blood sugar values fast, there is another dextrose drink they give him in small amounts, which contains 5-10 g carbohydrates. This is enough to help bring his glucose values back up. It is similar to the treatment recommendations provided to humans with diabetes where they are told to take 15 g of carbohydrates such as honey, hard candies, or juice to prevent a severe hypoglycemic episode.
Dr. Singleton noted that Quincy appears to have the koala equivalent is type 1 diabetes mellitus (T1DM).
Dr. Tsimikas noted “We are not finding the typical antibodies that we find in human T1DM. Quincy is showing low insulin levels, which is why it more closely resembles T1DM. We will be doing further analysis and comparisons with nondiabetic koalas in the future to see if it can be better differentiated.
While he appears to have type 1 diabetes, it’s not clear why he developed it, Dr. Singleton said.
While Quincy is only 3 years old, he’s a full-fledged adult in koala terms. Koalas typically live up to their mid-teens, she said.
This speechless patient still manages to communicate
The San Diego Zoo’s veterinary staff is monitoring Quincy and trying to understand how his glucose levels and daily insulin shots affect him. His tiny size has ruled out use of an insulin pump: Although the insulin pumps have been getting smaller and lighter, they are still too large to attach to our tiny friend. Especially since he would need both the CGM device and the pump, there is not a lot of surface area on his body for attachment of all the devices, according to Dr. Tsimikas.
Since Quincy is so tiny, insulin doses must be minuscule to avoid sending him into hypoglycemia, Dr. Tsimikas said. She said the koala’s medical team is planning to try using a NovoPen Echo injector with a half-unit of insulin.
Dr. Singleton noted that for now, “he’s maintaining his body weight, and he has days when he feels spunky. Sometimes, when he knows it’s breakfast time, and he hears his caretakers coming up the doorway with his breakfast, he’ll be very active on his perch.”
But he has sluggish days, too, when he’ll try to sleep in. Dr. Singleton keeps an eye out for grogginess and signs of weakness and hypoglycemia or hyperglycemia like “a little wobble in his step.”
“The biggest thing I’ve learned from Quincy is the value of his particular nonverbal cues,” she said. “I’m starting to understand when he feels like his sugars are a little high or a little low. I imagine that doctors and parents have the same challenges with little patients, along with figuring out how you communicate that this is supposed to help them.”
Dr. Tsimikas agreed, noting that she sees similarities between Quincy and patients who are hospitalized and can’t easily communicate. Now, “we can track the folks who are on the CGM and intervene earlier than before,” said Dr. Tsimikas, who’s part of a clinical trial team testing CGM devices in two hospitals. “It’s almost like having another vital sign.
“It is only when we have all the data on all the other factors that can influence blood sugar, such as eating patterns, insulin dose and timing, and activity level that we can more accurately adjust the medical interventions.” This requires collaboration between all the groups involved in Quincy’s care. In koalas, the collaboration is with the veterinarian, koala zookeepers, dietitian, and the technology monitoring team. Whereas, for humans, we need parents, care providers, diabetes educators, dietitians, and physicians.
It’s not clear if Quincy will need his CGM for the rest of his life. If he’s stable on a specific insulin dose, Dr. Tsimikas said, he may not need it. But it sounds like eucalyptus smoothies will always be a vital part of his regimen.
In the name of thoroughness, take note that Quincy is not the first diabetic zoo animal whose care involved physicians from Scripps. “We have had several other consultations for animals with diabetes. Nearly 25 years ago, a roller-skating chimpanzee with diabetes was brought to the Scripps Whittier Institute labs for evaluation and treatment recommendations. A few years later, one of our medical directors, Alberto Hayek, MD, advised on the care of Lune, a diabetic baboon at the San Diego Zoo, for insulin management. This time we are making house calls to the zoo to treat Quincy in his home environment. Each animal experience offers opportunities to expand our knowledge about diabetes care and exchange approaches that we might not otherwise be aware of. This has been fun and rewarding. I am looking forward to seeing further outcomes from our interactions with Quincy,” according to Dr. Tsimikas.
Dr. Tsimikas reports that her center conducts research with Dexcom and Novo Nordisk. Dr. Singleton reports no relevant disclosures.
Herceptin linked to doubling of HF risk in women with breast cancer
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
While trastuzumab clearly benefits patients with HER2-positive breast cancer at various stages of progression, concerns about heart failure persist. Studies have suggested that the drug doesn’t boost the risk of late cardiac events, but it’s not clear if this is due to mandated screening in these trials. The new study provides more evidence that adherence to screening guidelines is limited, and recent trials offer evidence that the general cardiac risk may be overblown. Future studies could be designed to offer insight into the wisdom of adjusting screening regimens based on stratification of risk. A meta-analysis could also be helpful, and the upcoming results of the SAFE-HEART study will provide information about the safety of anti-HER2 antibody therapy in patients with low but asymptomatic left-ventricular ejection fraction.
These comments are excerpted from a commentary by Chau T. Dang, MD, of Memorial Sloan Kettering Cancer Center, New York, and her associates (JACC: Cardiovasc Imaging. 2018 Aug;11[8]:1094-7). Most of the commentary authors report various disclosures.
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.
The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.
The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.
While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).
According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.
The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.
Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).
For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.
The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.
Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).
The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).
Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.
After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)
The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”
Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.
An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.
“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.
However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”
The researchers also noted that the findings suggest that screening has become more common in recent years.
“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”
The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.
SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.
FROM JACC: CARDIOVASCULAR IMAGING
Key clinical point: Women with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of heart failure, but most aren’t screened frequently.
Major finding: Patients who took trastuzumab were 2.01 times more likely to develop HF (HR, 95% CI, 1.72-2.36) than were those who didn’t. Of all patients who took the drug, fewer than half received recommended frequency of screening.
Study details: Analysis of 16,456 U.S. adult women with nonmetastatic breast cancer diagnosed from 2009 to 2014 and tracked through 2015. Of those, 4.2% developed HF.
Disclosures: The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors report grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors report no disclosures.
Source: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging 2018 Aug;11[8]1084-93.
Study supports meningococcal B vaccine in children with rare diseases
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
FROM PEDIATRICS
Key clinical point: The meningococcal B vaccine retained its strength in kids with two rare immunosuppressive diseases, but may be weaker in a third group.
Major finding: The vaccine’s effectiveness was roughly the same in healthy controls and in those with asplenia and splenic dysfunction, but it dipped in those with complement deficiency.
Study details: An open-label, multicenter analysis of children aged 2-17 years who received two doses over 2 months.
Disclosures: The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
Source: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
Questions abound about availability, legality of new cannabis-derived epilepsy drug
The first-ever federal approval of a marijuana-derived drug, Epidiolex (cannabidiol), comes with a cloud of complications.
Epidiolex is an oral solution of purified cannabidiol (CBD), a component of the marijuana plant that does not make people high.
According to the results of a phase 3 trial in patients with Lennox-Gastaut syndrome published earlier this year, median monthly drop seizures fell by 43.9% in a Epidiolex group compared with 21.8% in a placebo group (Lancet. 2018;391[10125]:1085-96). A 2017 study found that patients with Dravet syndrome who took the drug had fewer median convulsive seizures per month, dropping from 12.4 to 5.9, while there was barely a difference for the placebo group (N Engl J Med. 2017;376:2011-20). In both trials, patients received Epidiolex as an add-on treatment.
“There definitely are side effects such as sleepiness, abnormal liver function values, and other things that people will have to watch out for, such as interactions with other drugs,” Jacqueline A. French, MD, professor of neurology at New York University and chief scientific officer of the Epilepsy Foundation, said in an interview. “But it will definitely be a great benefit to some and a benefit to many.”
It’s not clear how the drug works, she said.
Greenwich Biosciences, the U.S. subsidiary of British drug maker GW Pharmaceuticals, plans to market Epidiolex this fall, spokesman Steve Schultz said in an interview. First, however, the U.S. Drug Enforcement Agency must reschedule the drug so it doesn’t fall under federal antimarijuana laws. It has 90 days after the FDA approval to do so, and its rescheduling is expected.
Then the focus will turn to the states, which have a crazy quilt of laws about marijuana and its medical use. “We’ve worked with the state legislators to enact laws or to modify laws to allow for our medicine to be made available,” Mr. Schultz said. “There may be one or two that we’re still working on.”
At issue: States and the District of Columbia have a wide variety of laws that appear to affect the sale of Epidiolex.
According to the website procon.org, 30 states and the District of Columbia allow medical marijuana, although the laws vary regarding what is allowed and do not address cannabis-derived pharmaceuticals.
Another 17 states have laws that address CBD specifically, often with language that allows its use to treat epilepsy in all or specific cases, according to procon.org.
In Oklahoma, an anticannabis law excludes “from the definition of marijuana ‘any federal Food and Drug Administration–approved cannabidiol drug or substance.’ ”
North Carolina attorney Rod Kight, who represents businesses in the cannabis industry, predicts that “once the federal government [via the DEA] changes the law, the states will fall in line. The only thing that would prevent them would be a lack of understanding of what’s going on.”
Meanwhile, many sellers of CBD-based products continue to promote their use as treatments for epilepsy and many other conditions.
Legal exceptions made by states for FDA-approved CBD-based drugs could affect access to unapproved CBD-based products. It’s also possible that Epidiolex could hurt sellers of cannabis products in other ways. “They’ll now have to compete with a drug made to a specific strength and purity, and that’s probably going to have some impact on their business,” William J. McNichol, adjunct professor at Rutgers Law School, Camden, N.J., said in an interview. “If you have a choice, are you going to choose aspirin I made myself in my artisan aspirin factory that the FDA never saw? Or aspirin made by Bayer?”
What’s next? For one, the FDA’s approval of Epidiolex seems likely to open the door for more cannabis-based medications. “The FDA is quite open to evaluating cannabinoid-based medicines as long as they go through their process,” said Mr. Schultz, the Greenwich Biosciences spokesman.
As for the legal front, Mr. Kight said potential changes in federal law could expand the legality of cannabis-based products by allowing them when they’re derived from “industrial hemp.” This could mean that patients with epilepsy will have more legal ways to buy CBD products.
Regardless of the legal situation, Mr. Kight said, “a physician can explain to patients across the board about how CBD might benefit them. The physician can say there are extract products that are out there and available over the counter.”
As for the maker of Epidiolex, GW Pharmaceuticals is recruiting for a phase 3 trial of a cannabinoid treatment for tuberous sclerosis complex, Mr. Schultz said. The results are due in the first half of 2019.
The company is also conducting cannabinoid research in the areas of autism and Rett syndrome, Mr. Schultz said, adding: “We also have done work in schizophrenia and in oncology and glioblastoma.”
Mr. Kight disclosed that he represents companies in the cannabis industry. Dr. French is president of the Epilepsy Study Consortium and disclosed working with multiple drug makers in the epilepsy field, including GW Pharmaceuticals. Dr. French receives fixed compensation by the consortium and is not paid by any pharmaceutical company. Mr. McNichol reported no relevant disclosures.
The first-ever federal approval of a marijuana-derived drug, Epidiolex (cannabidiol), comes with a cloud of complications.
Epidiolex is an oral solution of purified cannabidiol (CBD), a component of the marijuana plant that does not make people high.
According to the results of a phase 3 trial in patients with Lennox-Gastaut syndrome published earlier this year, median monthly drop seizures fell by 43.9% in a Epidiolex group compared with 21.8% in a placebo group (Lancet. 2018;391[10125]:1085-96). A 2017 study found that patients with Dravet syndrome who took the drug had fewer median convulsive seizures per month, dropping from 12.4 to 5.9, while there was barely a difference for the placebo group (N Engl J Med. 2017;376:2011-20). In both trials, patients received Epidiolex as an add-on treatment.
“There definitely are side effects such as sleepiness, abnormal liver function values, and other things that people will have to watch out for, such as interactions with other drugs,” Jacqueline A. French, MD, professor of neurology at New York University and chief scientific officer of the Epilepsy Foundation, said in an interview. “But it will definitely be a great benefit to some and a benefit to many.”
It’s not clear how the drug works, she said.
Greenwich Biosciences, the U.S. subsidiary of British drug maker GW Pharmaceuticals, plans to market Epidiolex this fall, spokesman Steve Schultz said in an interview. First, however, the U.S. Drug Enforcement Agency must reschedule the drug so it doesn’t fall under federal antimarijuana laws. It has 90 days after the FDA approval to do so, and its rescheduling is expected.
Then the focus will turn to the states, which have a crazy quilt of laws about marijuana and its medical use. “We’ve worked with the state legislators to enact laws or to modify laws to allow for our medicine to be made available,” Mr. Schultz said. “There may be one or two that we’re still working on.”
At issue: States and the District of Columbia have a wide variety of laws that appear to affect the sale of Epidiolex.
According to the website procon.org, 30 states and the District of Columbia allow medical marijuana, although the laws vary regarding what is allowed and do not address cannabis-derived pharmaceuticals.
Another 17 states have laws that address CBD specifically, often with language that allows its use to treat epilepsy in all or specific cases, according to procon.org.
In Oklahoma, an anticannabis law excludes “from the definition of marijuana ‘any federal Food and Drug Administration–approved cannabidiol drug or substance.’ ”
North Carolina attorney Rod Kight, who represents businesses in the cannabis industry, predicts that “once the federal government [via the DEA] changes the law, the states will fall in line. The only thing that would prevent them would be a lack of understanding of what’s going on.”
Meanwhile, many sellers of CBD-based products continue to promote their use as treatments for epilepsy and many other conditions.
Legal exceptions made by states for FDA-approved CBD-based drugs could affect access to unapproved CBD-based products. It’s also possible that Epidiolex could hurt sellers of cannabis products in other ways. “They’ll now have to compete with a drug made to a specific strength and purity, and that’s probably going to have some impact on their business,” William J. McNichol, adjunct professor at Rutgers Law School, Camden, N.J., said in an interview. “If you have a choice, are you going to choose aspirin I made myself in my artisan aspirin factory that the FDA never saw? Or aspirin made by Bayer?”
What’s next? For one, the FDA’s approval of Epidiolex seems likely to open the door for more cannabis-based medications. “The FDA is quite open to evaluating cannabinoid-based medicines as long as they go through their process,” said Mr. Schultz, the Greenwich Biosciences spokesman.
As for the legal front, Mr. Kight said potential changes in federal law could expand the legality of cannabis-based products by allowing them when they’re derived from “industrial hemp.” This could mean that patients with epilepsy will have more legal ways to buy CBD products.
Regardless of the legal situation, Mr. Kight said, “a physician can explain to patients across the board about how CBD might benefit them. The physician can say there are extract products that are out there and available over the counter.”
As for the maker of Epidiolex, GW Pharmaceuticals is recruiting for a phase 3 trial of a cannabinoid treatment for tuberous sclerosis complex, Mr. Schultz said. The results are due in the first half of 2019.
The company is also conducting cannabinoid research in the areas of autism and Rett syndrome, Mr. Schultz said, adding: “We also have done work in schizophrenia and in oncology and glioblastoma.”
Mr. Kight disclosed that he represents companies in the cannabis industry. Dr. French is president of the Epilepsy Study Consortium and disclosed working with multiple drug makers in the epilepsy field, including GW Pharmaceuticals. Dr. French receives fixed compensation by the consortium and is not paid by any pharmaceutical company. Mr. McNichol reported no relevant disclosures.
The first-ever federal approval of a marijuana-derived drug, Epidiolex (cannabidiol), comes with a cloud of complications.
Epidiolex is an oral solution of purified cannabidiol (CBD), a component of the marijuana plant that does not make people high.
According to the results of a phase 3 trial in patients with Lennox-Gastaut syndrome published earlier this year, median monthly drop seizures fell by 43.9% in a Epidiolex group compared with 21.8% in a placebo group (Lancet. 2018;391[10125]:1085-96). A 2017 study found that patients with Dravet syndrome who took the drug had fewer median convulsive seizures per month, dropping from 12.4 to 5.9, while there was barely a difference for the placebo group (N Engl J Med. 2017;376:2011-20). In both trials, patients received Epidiolex as an add-on treatment.
“There definitely are side effects such as sleepiness, abnormal liver function values, and other things that people will have to watch out for, such as interactions with other drugs,” Jacqueline A. French, MD, professor of neurology at New York University and chief scientific officer of the Epilepsy Foundation, said in an interview. “But it will definitely be a great benefit to some and a benefit to many.”
It’s not clear how the drug works, she said.
Greenwich Biosciences, the U.S. subsidiary of British drug maker GW Pharmaceuticals, plans to market Epidiolex this fall, spokesman Steve Schultz said in an interview. First, however, the U.S. Drug Enforcement Agency must reschedule the drug so it doesn’t fall under federal antimarijuana laws. It has 90 days after the FDA approval to do so, and its rescheduling is expected.
Then the focus will turn to the states, which have a crazy quilt of laws about marijuana and its medical use. “We’ve worked with the state legislators to enact laws or to modify laws to allow for our medicine to be made available,” Mr. Schultz said. “There may be one or two that we’re still working on.”
At issue: States and the District of Columbia have a wide variety of laws that appear to affect the sale of Epidiolex.
According to the website procon.org, 30 states and the District of Columbia allow medical marijuana, although the laws vary regarding what is allowed and do not address cannabis-derived pharmaceuticals.
Another 17 states have laws that address CBD specifically, often with language that allows its use to treat epilepsy in all or specific cases, according to procon.org.
In Oklahoma, an anticannabis law excludes “from the definition of marijuana ‘any federal Food and Drug Administration–approved cannabidiol drug or substance.’ ”
North Carolina attorney Rod Kight, who represents businesses in the cannabis industry, predicts that “once the federal government [via the DEA] changes the law, the states will fall in line. The only thing that would prevent them would be a lack of understanding of what’s going on.”
Meanwhile, many sellers of CBD-based products continue to promote their use as treatments for epilepsy and many other conditions.
Legal exceptions made by states for FDA-approved CBD-based drugs could affect access to unapproved CBD-based products. It’s also possible that Epidiolex could hurt sellers of cannabis products in other ways. “They’ll now have to compete with a drug made to a specific strength and purity, and that’s probably going to have some impact on their business,” William J. McNichol, adjunct professor at Rutgers Law School, Camden, N.J., said in an interview. “If you have a choice, are you going to choose aspirin I made myself in my artisan aspirin factory that the FDA never saw? Or aspirin made by Bayer?”
What’s next? For one, the FDA’s approval of Epidiolex seems likely to open the door for more cannabis-based medications. “The FDA is quite open to evaluating cannabinoid-based medicines as long as they go through their process,” said Mr. Schultz, the Greenwich Biosciences spokesman.
As for the legal front, Mr. Kight said potential changes in federal law could expand the legality of cannabis-based products by allowing them when they’re derived from “industrial hemp.” This could mean that patients with epilepsy will have more legal ways to buy CBD products.
Regardless of the legal situation, Mr. Kight said, “a physician can explain to patients across the board about how CBD might benefit them. The physician can say there are extract products that are out there and available over the counter.”
As for the maker of Epidiolex, GW Pharmaceuticals is recruiting for a phase 3 trial of a cannabinoid treatment for tuberous sclerosis complex, Mr. Schultz said. The results are due in the first half of 2019.
The company is also conducting cannabinoid research in the areas of autism and Rett syndrome, Mr. Schultz said, adding: “We also have done work in schizophrenia and in oncology and glioblastoma.”
Mr. Kight disclosed that he represents companies in the cannabis industry. Dr. French is president of the Epilepsy Study Consortium and disclosed working with multiple drug makers in the epilepsy field, including GW Pharmaceuticals. Dr. French receives fixed compensation by the consortium and is not paid by any pharmaceutical company. Mr. McNichol reported no relevant disclosures.
Omega-3 heart benefit: Just another fish tale?
There’s more evidence that the vaunted reputation of fish oil is all wet: An updated Cochrane Library review finds that boosting two components of omega-3 fats – mainly through supplements such as fish oil – has little or no impact on cardiac health or overall mortality.
“Although EPA and DHA reduce triglycerides, supplementary omega-3 fats are probably not useful for preventing or treating heart and circulatory diseases,” the researchers wrote, referring to eicosapentaenoic acid and docosahexaenoic acid, two sources of omega-3 fats in fish.
They did find signs that boosting intake of plant-based alpha-linolenic acid (ALA) “may be slightly protective for some heart and circulatory diseases.” However, they deemed the evidence to be of low quality compared with the high- to moderate-quality evidence supporting the conclusions regarding omega-3 fats from fish.
The review, led by Asmaa S. Abdelhamid, MBBCH, MSc, MD, of the University of East Anglia, was commissioned by the World Health Organization and published on July 18, 2018, in Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD003177.pub3). It updates a 2004 Cochrane Library review.
As the review notes, “there is a great deal of public belief in the cardiovascular benefits of omega-3 fats.” But research in recent years has questioned the benefits of fish oil supplementation.
For the new review, the researchers focused on studies that boosted omega-3 fat intake using EPA, DHA and ALA.
The researchers included 79 randomized controlled trials with a total of more than 112,000 adult participants. The studies examined the cardiac and circulatory system effects of greater omega-3 consumption for at least a year compared with controls. Most trials tested supplementation with capsules, but some relied on boosting intake of foods or simply making dietary recommendations.
The studies were conducted in North America, Europe, Australia, and Asia. Researchers determined that 25 trials were designed well enough to be deemed “very trustworthy.”
According to the review’s meta-analysis, increasing intake of long-chain omega-3 fatty acids (EPA and DHA) had little to no effect on all-cause mortality (relative risk, 0.98; 39 trials), cardiovascular mortality (RR, 0.95; 25 trials), cardiovascular events (RR, 0.99; 38 trials), coronary heart disease mortality (RR, 0.93; 21 trials) and arrhythmia (RR, 0.97; 28 trials), while there was a potential boost in stroke risk (RR, 1.06; 28 trials).
The investigators noted that the relative risk of coronary heart disease events fell (RR, 0.93; 28 trials), but this did not hold up after sensitivity analysis. All these trials were deemed of moderate or high quality.
As for increased ALA intake, the researchers found little or no effect on all-cause mortality (RR, 1.01; four trials) and cardiovascular mortality (RR, 0.96; four trials) or coronary heart disease events (RR, 1.00, four trials).
Although the researchers deemed the evidence on ALA to be of low quality, there’s a possible decreased risk of cardiovascular events (RR, 0.95; five trials), coronary heart disease mortality (RR, 0.95; three trials) and arrhythmia (RR, 0.79; one trial). It’s not clear if increased ALA intake affects stroke risk.
“There was no evidence that increasing LCn3 [long-chain omega-3 fatty acids] or ALA altered serious adverse events, adiposity, or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence),” the researchers wrote.
Why have some earlier studies suggested a significant effect, enough to help convince millions of Americans to add fish oil pills to their diets? “Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias,” the researchers wrote. Robert A. Vogel, MD, a cardiologist at the University of Colorado Denver who is familiar with the review findings, said in an interview that “it’s hard to recommend taking fish oil for heart disease. Even if there’s some effect, it’s got to be a very small, 5%-7% reduction at the best.
“That is not to say that there isn’t an effect on triglycerides,” he added. “[Fish oil] is an accepted way of reducing triglycerides. But you don’t reduce triglycerides to reduce heart disease. There are other risks to high triglycerides, such as pancreatitis.”
Dr. Vogel said he’s never taken fish oil supplements, but he does eat fish 5-6 times a week.
The review was funded by the University of East Anglia, Cochrane Heart Group, and the National Institute for Health Research. The review authors reported no relevant disclosures. Dr. Vogel disclosed consulting for the Pritikin Longevity Center.
SOURCE: Abdelhamid AS et al. Cochrane Database Syst Rev. 2018 Jul 18. doi: 10.1002/14651858.CD003177.pub3.
There’s more evidence that the vaunted reputation of fish oil is all wet: An updated Cochrane Library review finds that boosting two components of omega-3 fats – mainly through supplements such as fish oil – has little or no impact on cardiac health or overall mortality.
“Although EPA and DHA reduce triglycerides, supplementary omega-3 fats are probably not useful for preventing or treating heart and circulatory diseases,” the researchers wrote, referring to eicosapentaenoic acid and docosahexaenoic acid, two sources of omega-3 fats in fish.
They did find signs that boosting intake of plant-based alpha-linolenic acid (ALA) “may be slightly protective for some heart and circulatory diseases.” However, they deemed the evidence to be of low quality compared with the high- to moderate-quality evidence supporting the conclusions regarding omega-3 fats from fish.
The review, led by Asmaa S. Abdelhamid, MBBCH, MSc, MD, of the University of East Anglia, was commissioned by the World Health Organization and published on July 18, 2018, in Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD003177.pub3). It updates a 2004 Cochrane Library review.
As the review notes, “there is a great deal of public belief in the cardiovascular benefits of omega-3 fats.” But research in recent years has questioned the benefits of fish oil supplementation.
For the new review, the researchers focused on studies that boosted omega-3 fat intake using EPA, DHA and ALA.
The researchers included 79 randomized controlled trials with a total of more than 112,000 adult participants. The studies examined the cardiac and circulatory system effects of greater omega-3 consumption for at least a year compared with controls. Most trials tested supplementation with capsules, but some relied on boosting intake of foods or simply making dietary recommendations.
The studies were conducted in North America, Europe, Australia, and Asia. Researchers determined that 25 trials were designed well enough to be deemed “very trustworthy.”
According to the review’s meta-analysis, increasing intake of long-chain omega-3 fatty acids (EPA and DHA) had little to no effect on all-cause mortality (relative risk, 0.98; 39 trials), cardiovascular mortality (RR, 0.95; 25 trials), cardiovascular events (RR, 0.99; 38 trials), coronary heart disease mortality (RR, 0.93; 21 trials) and arrhythmia (RR, 0.97; 28 trials), while there was a potential boost in stroke risk (RR, 1.06; 28 trials).
The investigators noted that the relative risk of coronary heart disease events fell (RR, 0.93; 28 trials), but this did not hold up after sensitivity analysis. All these trials were deemed of moderate or high quality.
As for increased ALA intake, the researchers found little or no effect on all-cause mortality (RR, 1.01; four trials) and cardiovascular mortality (RR, 0.96; four trials) or coronary heart disease events (RR, 1.00, four trials).
Although the researchers deemed the evidence on ALA to be of low quality, there’s a possible decreased risk of cardiovascular events (RR, 0.95; five trials), coronary heart disease mortality (RR, 0.95; three trials) and arrhythmia (RR, 0.79; one trial). It’s not clear if increased ALA intake affects stroke risk.
“There was no evidence that increasing LCn3 [long-chain omega-3 fatty acids] or ALA altered serious adverse events, adiposity, or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence),” the researchers wrote.
Why have some earlier studies suggested a significant effect, enough to help convince millions of Americans to add fish oil pills to their diets? “Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias,” the researchers wrote. Robert A. Vogel, MD, a cardiologist at the University of Colorado Denver who is familiar with the review findings, said in an interview that “it’s hard to recommend taking fish oil for heart disease. Even if there’s some effect, it’s got to be a very small, 5%-7% reduction at the best.
“That is not to say that there isn’t an effect on triglycerides,” he added. “[Fish oil] is an accepted way of reducing triglycerides. But you don’t reduce triglycerides to reduce heart disease. There are other risks to high triglycerides, such as pancreatitis.”
Dr. Vogel said he’s never taken fish oil supplements, but he does eat fish 5-6 times a week.
The review was funded by the University of East Anglia, Cochrane Heart Group, and the National Institute for Health Research. The review authors reported no relevant disclosures. Dr. Vogel disclosed consulting for the Pritikin Longevity Center.
SOURCE: Abdelhamid AS et al. Cochrane Database Syst Rev. 2018 Jul 18. doi: 10.1002/14651858.CD003177.pub3.
There’s more evidence that the vaunted reputation of fish oil is all wet: An updated Cochrane Library review finds that boosting two components of omega-3 fats – mainly through supplements such as fish oil – has little or no impact on cardiac health or overall mortality.
“Although EPA and DHA reduce triglycerides, supplementary omega-3 fats are probably not useful for preventing or treating heart and circulatory diseases,” the researchers wrote, referring to eicosapentaenoic acid and docosahexaenoic acid, two sources of omega-3 fats in fish.
They did find signs that boosting intake of plant-based alpha-linolenic acid (ALA) “may be slightly protective for some heart and circulatory diseases.” However, they deemed the evidence to be of low quality compared with the high- to moderate-quality evidence supporting the conclusions regarding omega-3 fats from fish.
The review, led by Asmaa S. Abdelhamid, MBBCH, MSc, MD, of the University of East Anglia, was commissioned by the World Health Organization and published on July 18, 2018, in Cochrane Database of Systematic Reviews (doi: 10.1002/14651858.CD003177.pub3). It updates a 2004 Cochrane Library review.
As the review notes, “there is a great deal of public belief in the cardiovascular benefits of omega-3 fats.” But research in recent years has questioned the benefits of fish oil supplementation.
For the new review, the researchers focused on studies that boosted omega-3 fat intake using EPA, DHA and ALA.
The researchers included 79 randomized controlled trials with a total of more than 112,000 adult participants. The studies examined the cardiac and circulatory system effects of greater omega-3 consumption for at least a year compared with controls. Most trials tested supplementation with capsules, but some relied on boosting intake of foods or simply making dietary recommendations.
The studies were conducted in North America, Europe, Australia, and Asia. Researchers determined that 25 trials were designed well enough to be deemed “very trustworthy.”
According to the review’s meta-analysis, increasing intake of long-chain omega-3 fatty acids (EPA and DHA) had little to no effect on all-cause mortality (relative risk, 0.98; 39 trials), cardiovascular mortality (RR, 0.95; 25 trials), cardiovascular events (RR, 0.99; 38 trials), coronary heart disease mortality (RR, 0.93; 21 trials) and arrhythmia (RR, 0.97; 28 trials), while there was a potential boost in stroke risk (RR, 1.06; 28 trials).
The investigators noted that the relative risk of coronary heart disease events fell (RR, 0.93; 28 trials), but this did not hold up after sensitivity analysis. All these trials were deemed of moderate or high quality.
As for increased ALA intake, the researchers found little or no effect on all-cause mortality (RR, 1.01; four trials) and cardiovascular mortality (RR, 0.96; four trials) or coronary heart disease events (RR, 1.00, four trials).
Although the researchers deemed the evidence on ALA to be of low quality, there’s a possible decreased risk of cardiovascular events (RR, 0.95; five trials), coronary heart disease mortality (RR, 0.95; three trials) and arrhythmia (RR, 0.79; one trial). It’s not clear if increased ALA intake affects stroke risk.
“There was no evidence that increasing LCn3 [long-chain omega-3 fatty acids] or ALA altered serious adverse events, adiposity, or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence),” the researchers wrote.
Why have some earlier studies suggested a significant effect, enough to help convince millions of Americans to add fish oil pills to their diets? “Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias,” the researchers wrote. Robert A. Vogel, MD, a cardiologist at the University of Colorado Denver who is familiar with the review findings, said in an interview that “it’s hard to recommend taking fish oil for heart disease. Even if there’s some effect, it’s got to be a very small, 5%-7% reduction at the best.
“That is not to say that there isn’t an effect on triglycerides,” he added. “[Fish oil] is an accepted way of reducing triglycerides. But you don’t reduce triglycerides to reduce heart disease. There are other risks to high triglycerides, such as pancreatitis.”
Dr. Vogel said he’s never taken fish oil supplements, but he does eat fish 5-6 times a week.
The review was funded by the University of East Anglia, Cochrane Heart Group, and the National Institute for Health Research. The review authors reported no relevant disclosures. Dr. Vogel disclosed consulting for the Pritikin Longevity Center.
SOURCE: Abdelhamid AS et al. Cochrane Database Syst Rev. 2018 Jul 18. doi: 10.1002/14651858.CD003177.pub3.
FROM COCHRANE DATABASE OF SYSTEMATIC REVIEWS
Key clinical point: .
Major finding: Increased intake of fish-based omega-3 fats, mainly supplements, seems to barely affect various cardiac/circulatory outcomes. Increased intake of plant-based alpha-linolenic acid may be slightly helpful.
Study details: Review of 79 randomized controlled trials with more than 112,000 adult subjects.
Disclosures: The review was funded by the University of East Anglia, Cochrane Heart Group, and the National Institute for Health Research. The review authors reported no relevant disclosures.
Source: Abdelhamid AS et al. Cochrane Database Syst Rev. 2018 Jul 18. doi: 10.1002/14651858.CD003177.pub3.
Endocrinologists clash over routine CGM during pregnancy
ORLANDO – Diabetes and pregnancy aren’t a good mix, but what about pregnancy and continuous glucose monitors (CGMs)? In a polite but pointed debate, two endocrinologists used each other’s studies as evidence to support their opposing perspectives about routine GCM use by diabetic women during pregnancy.
“This topic shouldn’t really be debated because the evidence is clear” in favor of CGM, said Denice S. Feig, MD, MSc, FRCPC, of the University of Toronto and Mt. Sinai Hospital, also in Toronto, in a presentation at the annual scientific sessions of the American Diabetes Association.
However, Elisabeth R. Mathiesen, MD, DMSc, of Rigshospitalet in Copenhagen, rebutted. She said her own research suggests CGM use may lead to larger babies and more premature births, convincing her to “say no to uncritical use of CGM in pregnancy.”
At issue: What is the best routine treatment for diabetic women before, during, and after pregnancy? As the American Diabetes Association noted in its 2018 Standards of Medical Care in Diabetes report, “specific risks of uncontrolled diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia, among others. In addition, diabetes in pregnancy may increase the risk of obesity and type 2 diabetes [mellitus] in offspring later in life.”
In her presentation, Dr. Feig pointed to a 2017 study she led that examined the effectiveness of continuous, real-time CGM on women with type 1 diabetes mellitus who were pregnant or planning to become pregnant (Lancet. 2017 Nov 25;390(10110):2347-2359).
“The study, in effect, was two parallel, randomized trials, one in those who planned pregnancy and one in those who were pregnant,” Dr. Feig said.
Participants, aged 18-40 years, from 31 hospitals in seven European and North American nations, had to have hemoglobin A1c levels greater than or equal to 6.5% during pregnancy or greater than or equal to 7% while planning pregnancy to be included in the study.
“We had a run-in phase to make sure they were able and willing to wear the CGM. Then we had 215 women in the pregnancy arm and 110 in the prepregnancy group randomized to real-time continuous CGM or standard care,” Dr. Feig said. The study ran for 34 weeks in the pregnant patients and for 24 weeks or until conception in the other women.
According to Dr. Feig, 70% of pregnant participants used CGM devices for more than 75% of the time. Compared with the control group, HbA1c levels in those who used CGM fell by 0.19% (P = .0207). The researchers also reported that women in the CGM group spent 100 more minutes a day within the glucose target range.
No differences in outcomes such as gestational age at delivery and rate of preterm delivery was found, although incidence of large-for-gestational-age infants, hypoglycemia requiring dextrose infusion, and neonatal ICU admission were lower in the CGM group to a statistically significant degree. “The numbers needed to treat were very small at six to eight women to reduce one of these events,” said Dr. Feig, who added that the numbers suggest the potential for cost savings.
Whatever the case, she said, “what price would you place on your baby avoiding a prolonged stay in the NICU? I think [it’s] priceless.”
She added that 80% of participants reported having trouble with the devices, which she attributed to the technology being old.
As for the planned pregnancy group, the study noted that “it did not have sufficient power to detect the magnitude of differences that were significant in the pregnancy trial.”
However, Dr. Feig said the study showed a trend toward lower HbA1c levels among CGM users in this population in which “tight glycemic control is absolutely paramount,” and that other studies also provide evidence supporting CGM use through the breastfeeding period.
Dr. Feig also pointed to a similar 2013 study coauthored by Dr. Mathiesen, her debate opponent. Dr. Feig said its findings are weakened because participants used CGM intermittently. She also pointed to the low participation (64%) in CGM by women assigned to a CGM group. (Diabetes Care. 2013 Jul;36[7]:1877-83)
In that study, researchers assigned 123 Danish women with type 1 diabetes mellitus and 31 women with type 2 diabetes mellitus to use real-time CGM for 6 days at various points in pregnancy or to only engage in routine care (including self-monitored plasma glucose seven times daily).
Researchers found no difference in HbA1c levels at 33 weeks between the groups, and they found similar rates of severe hypoglycemia and perinatal outcomes such as large-for-gestational-age infants.
These results, Dr. Mathiesen said, make her skeptical of a blanket recommendation to use CGM in pregnancy. Women aren’t eager to upload their glucose readings, making it difficult for doctors to make adjustments. “My women are Vikings. They come from Denmark,” she said, but “even these women don’t upload their glucose data between visits. ... I rarely have women who upload their data and look at their curves themselves. I think that’s a major disadvantage.”
Dr. Mathiesen also pointed to Dr. Feig’s study and noted that many women used CGM less than 75% of the time. In addition, 80% reported problems with the technology. “I’ve seen lots of skin problems with sensors. One lady used CGM during pregnancy; 4 years later, during another pregnancy, she showed me the mark of her sensor.”
Finally, the cost of CGM use is high considering the ongoing expense of the devices and the nurse time needed to upload data in the clinic. “As a rough estimate, the cost of CGM use in about 20 women during their pregnancies is the cost of the salary for one nurse per year,” she said.
Dr. Feig reported speaking fees from Medtronic, which provided CGM devices at reduced cost to her trial. Dr. Mathiesen reported research funding from the Novo Nordisk Foundation and speaker fees from Novo Nordisk, Lilly, AstraZeneca, and Sanofi-Aventis.
ORLANDO – Diabetes and pregnancy aren’t a good mix, but what about pregnancy and continuous glucose monitors (CGMs)? In a polite but pointed debate, two endocrinologists used each other’s studies as evidence to support their opposing perspectives about routine GCM use by diabetic women during pregnancy.
“This topic shouldn’t really be debated because the evidence is clear” in favor of CGM, said Denice S. Feig, MD, MSc, FRCPC, of the University of Toronto and Mt. Sinai Hospital, also in Toronto, in a presentation at the annual scientific sessions of the American Diabetes Association.
However, Elisabeth R. Mathiesen, MD, DMSc, of Rigshospitalet in Copenhagen, rebutted. She said her own research suggests CGM use may lead to larger babies and more premature births, convincing her to “say no to uncritical use of CGM in pregnancy.”
At issue: What is the best routine treatment for diabetic women before, during, and after pregnancy? As the American Diabetes Association noted in its 2018 Standards of Medical Care in Diabetes report, “specific risks of uncontrolled diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia, among others. In addition, diabetes in pregnancy may increase the risk of obesity and type 2 diabetes [mellitus] in offspring later in life.”
In her presentation, Dr. Feig pointed to a 2017 study she led that examined the effectiveness of continuous, real-time CGM on women with type 1 diabetes mellitus who were pregnant or planning to become pregnant (Lancet. 2017 Nov 25;390(10110):2347-2359).
“The study, in effect, was two parallel, randomized trials, one in those who planned pregnancy and one in those who were pregnant,” Dr. Feig said.
Participants, aged 18-40 years, from 31 hospitals in seven European and North American nations, had to have hemoglobin A1c levels greater than or equal to 6.5% during pregnancy or greater than or equal to 7% while planning pregnancy to be included in the study.
“We had a run-in phase to make sure they were able and willing to wear the CGM. Then we had 215 women in the pregnancy arm and 110 in the prepregnancy group randomized to real-time continuous CGM or standard care,” Dr. Feig said. The study ran for 34 weeks in the pregnant patients and for 24 weeks or until conception in the other women.
According to Dr. Feig, 70% of pregnant participants used CGM devices for more than 75% of the time. Compared with the control group, HbA1c levels in those who used CGM fell by 0.19% (P = .0207). The researchers also reported that women in the CGM group spent 100 more minutes a day within the glucose target range.
No differences in outcomes such as gestational age at delivery and rate of preterm delivery was found, although incidence of large-for-gestational-age infants, hypoglycemia requiring dextrose infusion, and neonatal ICU admission were lower in the CGM group to a statistically significant degree. “The numbers needed to treat were very small at six to eight women to reduce one of these events,” said Dr. Feig, who added that the numbers suggest the potential for cost savings.
Whatever the case, she said, “what price would you place on your baby avoiding a prolonged stay in the NICU? I think [it’s] priceless.”
She added that 80% of participants reported having trouble with the devices, which she attributed to the technology being old.
As for the planned pregnancy group, the study noted that “it did not have sufficient power to detect the magnitude of differences that were significant in the pregnancy trial.”
However, Dr. Feig said the study showed a trend toward lower HbA1c levels among CGM users in this population in which “tight glycemic control is absolutely paramount,” and that other studies also provide evidence supporting CGM use through the breastfeeding period.
Dr. Feig also pointed to a similar 2013 study coauthored by Dr. Mathiesen, her debate opponent. Dr. Feig said its findings are weakened because participants used CGM intermittently. She also pointed to the low participation (64%) in CGM by women assigned to a CGM group. (Diabetes Care. 2013 Jul;36[7]:1877-83)
In that study, researchers assigned 123 Danish women with type 1 diabetes mellitus and 31 women with type 2 diabetes mellitus to use real-time CGM for 6 days at various points in pregnancy or to only engage in routine care (including self-monitored plasma glucose seven times daily).
Researchers found no difference in HbA1c levels at 33 weeks between the groups, and they found similar rates of severe hypoglycemia and perinatal outcomes such as large-for-gestational-age infants.
These results, Dr. Mathiesen said, make her skeptical of a blanket recommendation to use CGM in pregnancy. Women aren’t eager to upload their glucose readings, making it difficult for doctors to make adjustments. “My women are Vikings. They come from Denmark,” she said, but “even these women don’t upload their glucose data between visits. ... I rarely have women who upload their data and look at their curves themselves. I think that’s a major disadvantage.”
Dr. Mathiesen also pointed to Dr. Feig’s study and noted that many women used CGM less than 75% of the time. In addition, 80% reported problems with the technology. “I’ve seen lots of skin problems with sensors. One lady used CGM during pregnancy; 4 years later, during another pregnancy, she showed me the mark of her sensor.”
Finally, the cost of CGM use is high considering the ongoing expense of the devices and the nurse time needed to upload data in the clinic. “As a rough estimate, the cost of CGM use in about 20 women during their pregnancies is the cost of the salary for one nurse per year,” she said.
Dr. Feig reported speaking fees from Medtronic, which provided CGM devices at reduced cost to her trial. Dr. Mathiesen reported research funding from the Novo Nordisk Foundation and speaker fees from Novo Nordisk, Lilly, AstraZeneca, and Sanofi-Aventis.
ORLANDO – Diabetes and pregnancy aren’t a good mix, but what about pregnancy and continuous glucose monitors (CGMs)? In a polite but pointed debate, two endocrinologists used each other’s studies as evidence to support their opposing perspectives about routine GCM use by diabetic women during pregnancy.
“This topic shouldn’t really be debated because the evidence is clear” in favor of CGM, said Denice S. Feig, MD, MSc, FRCPC, of the University of Toronto and Mt. Sinai Hospital, also in Toronto, in a presentation at the annual scientific sessions of the American Diabetes Association.
However, Elisabeth R. Mathiesen, MD, DMSc, of Rigshospitalet in Copenhagen, rebutted. She said her own research suggests CGM use may lead to larger babies and more premature births, convincing her to “say no to uncritical use of CGM in pregnancy.”
At issue: What is the best routine treatment for diabetic women before, during, and after pregnancy? As the American Diabetes Association noted in its 2018 Standards of Medical Care in Diabetes report, “specific risks of uncontrolled diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia, among others. In addition, diabetes in pregnancy may increase the risk of obesity and type 2 diabetes [mellitus] in offspring later in life.”
In her presentation, Dr. Feig pointed to a 2017 study she led that examined the effectiveness of continuous, real-time CGM on women with type 1 diabetes mellitus who were pregnant or planning to become pregnant (Lancet. 2017 Nov 25;390(10110):2347-2359).
“The study, in effect, was two parallel, randomized trials, one in those who planned pregnancy and one in those who were pregnant,” Dr. Feig said.
Participants, aged 18-40 years, from 31 hospitals in seven European and North American nations, had to have hemoglobin A1c levels greater than or equal to 6.5% during pregnancy or greater than or equal to 7% while planning pregnancy to be included in the study.
“We had a run-in phase to make sure they were able and willing to wear the CGM. Then we had 215 women in the pregnancy arm and 110 in the prepregnancy group randomized to real-time continuous CGM or standard care,” Dr. Feig said. The study ran for 34 weeks in the pregnant patients and for 24 weeks or until conception in the other women.
According to Dr. Feig, 70% of pregnant participants used CGM devices for more than 75% of the time. Compared with the control group, HbA1c levels in those who used CGM fell by 0.19% (P = .0207). The researchers also reported that women in the CGM group spent 100 more minutes a day within the glucose target range.
No differences in outcomes such as gestational age at delivery and rate of preterm delivery was found, although incidence of large-for-gestational-age infants, hypoglycemia requiring dextrose infusion, and neonatal ICU admission were lower in the CGM group to a statistically significant degree. “The numbers needed to treat were very small at six to eight women to reduce one of these events,” said Dr. Feig, who added that the numbers suggest the potential for cost savings.
Whatever the case, she said, “what price would you place on your baby avoiding a prolonged stay in the NICU? I think [it’s] priceless.”
She added that 80% of participants reported having trouble with the devices, which she attributed to the technology being old.
As for the planned pregnancy group, the study noted that “it did not have sufficient power to detect the magnitude of differences that were significant in the pregnancy trial.”
However, Dr. Feig said the study showed a trend toward lower HbA1c levels among CGM users in this population in which “tight glycemic control is absolutely paramount,” and that other studies also provide evidence supporting CGM use through the breastfeeding period.
Dr. Feig also pointed to a similar 2013 study coauthored by Dr. Mathiesen, her debate opponent. Dr. Feig said its findings are weakened because participants used CGM intermittently. She also pointed to the low participation (64%) in CGM by women assigned to a CGM group. (Diabetes Care. 2013 Jul;36[7]:1877-83)
In that study, researchers assigned 123 Danish women with type 1 diabetes mellitus and 31 women with type 2 diabetes mellitus to use real-time CGM for 6 days at various points in pregnancy or to only engage in routine care (including self-monitored plasma glucose seven times daily).
Researchers found no difference in HbA1c levels at 33 weeks between the groups, and they found similar rates of severe hypoglycemia and perinatal outcomes such as large-for-gestational-age infants.
These results, Dr. Mathiesen said, make her skeptical of a blanket recommendation to use CGM in pregnancy. Women aren’t eager to upload their glucose readings, making it difficult for doctors to make adjustments. “My women are Vikings. They come from Denmark,” she said, but “even these women don’t upload their glucose data between visits. ... I rarely have women who upload their data and look at their curves themselves. I think that’s a major disadvantage.”
Dr. Mathiesen also pointed to Dr. Feig’s study and noted that many women used CGM less than 75% of the time. In addition, 80% reported problems with the technology. “I’ve seen lots of skin problems with sensors. One lady used CGM during pregnancy; 4 years later, during another pregnancy, she showed me the mark of her sensor.”
Finally, the cost of CGM use is high considering the ongoing expense of the devices and the nurse time needed to upload data in the clinic. “As a rough estimate, the cost of CGM use in about 20 women during their pregnancies is the cost of the salary for one nurse per year,” she said.
Dr. Feig reported speaking fees from Medtronic, which provided CGM devices at reduced cost to her trial. Dr. Mathiesen reported research funding from the Novo Nordisk Foundation and speaker fees from Novo Nordisk, Lilly, AstraZeneca, and Sanofi-Aventis.
EXPERT ANALYSIS FROM ADA 2018
Neuroimaging may often be unneeded in ED seizure treatment
Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests. 
“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”
As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”
The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.
“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”
For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)
The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.
Of the total nonindex seizures, 46% of those resulted in neuroimaging.
“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.
False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.
“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”
At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.
A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.
As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”
The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.
No study funding was reported, and the authors reported no relevant disclosures.
SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518
Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.
“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”
As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”
The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.
“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”
For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)
The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.
Of the total nonindex seizures, 46% of those resulted in neuroimaging.
“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.
False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.
“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”
At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.
A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.
As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”
The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.
No study funding was reported, and the authors reported no relevant disclosures.
SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518
Neuroimaging may be appropriate only for specific types of patients with recurrent seizures who present at emergency departments because the scans are otherwise unlikely to prompt acute changes in treatment, a new multicenter study suggests.
“Going forward, our results should help ED providers determine which patients are more likely to derive benefit from neuroimaging and which patients are not likely to benefit,” lead author Martin Salinsky, MD, of Oregon Health & Science University, Portland, said in an interview. “They can be more selective in ordering scans and reduce the total number obtained.”
As the study authors noted in their report, published July 18 in Epilepsia, “head CT is generally considered a benign procedure. However, overuse is problematic.”
The scans are costly and expose patients to radiation equivalent to 10 chest x-rays, the authors wrote. Scans can complicate care by clogging ED work flow and producing false positives, and patients often seize while undergoing scans, creating even more complications, they added.
“There is very little information in the medical literature that would help guide ED providers in their decision of whether to obtain neuroimaging on a patient who presents with a recurrent seizure,” Dr. Salinsky said. “Without this information, the tendency is to be cautious and obtain scans in more patients.”
For the study, the researchers tracked 822 consecutive ED visits for nonindex – recurrent – epileptic seizures at Oregon Health & Science University and VA Portland Health Care medical centers. (Nonindex seizures accounted for 78% of the total seizures that prompted ED care.)
The study subjects were adults treated for seizure as the main complaint. Patients who had a history of seizures but hadn’t had one for at least 5 years were excluded.
Of the total nonindex seizures, 46% of those resulted in neuroimaging.
“The overall yield of neuroimaging in this patient group was 2%-3%,” Dr. Salinsky said, referring to the percentage of patients whose scans resulted in an acute change in management.
False positives due to imaging artifacts were subsequently discovered in 3 of the 11 patients whose neuroimaging prompted an acute change in management. When the false positives were removed, the yield of acute management changes prompted by neuroimaging decreased to 2.1% overall.
“Three clinical factors – acute head trauma, prolonged alteration of consciousness, and focal neurological examination [at presentation] – were associated with an increased yield of imaging,” he said. “Absent all three factors, the yield in our patients was zero.”
At the two medical centers, the percentages of patients with acute head trauma were 10% and 15%. Prolonged alteration of consciousness occurred in 6% at both centers, and focal neurological examination at presentation was observed in 12% and 14%.
A fourth factor, presentation with status epilepticus/acute repetitive seizures, “bordered on statistical significance and might have reached significance in a larger series,” the authors wrote.
As they put it, “these results support a more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at the time of presentation. ... without specific indications, ED neuroimaging for nonindex seizures is unlikely to result in an acute change in care.”
The study authors estimated that hundreds of millions of dollars could be saved annually in the United States if neuroimaging in these ED patients could be cut in half.
No study funding was reported, and the authors reported no relevant disclosures.
SOURCE: Salinsky M et al. Epilepsia. 2018 July 18. doi: 10.1111/epi.14518
FROM EPILEPSIA
Key clinical point: In emergency departments, patients with seizure disorders and nonindex seizures may need neuroimaging only if they have acute head trauma, prolonged alteration of consciousness, or focal neurological examination at presentation.
Major finding: Absent the three factors above, neuroimaging did not prompt any acute changes in management.
Study details: Retrospective examination of 822 consecutive ED visits for nonindex seizures in patients with seizure disorders at two medical centers.
Disclosures: No study funding was reported, and the study authors reported no relevant disclosures.
Source: Salinsky M et al. Epilepsia. 2018 Jul 18. doi: 10.1111/epi.14518.
Special care advised for HIV-infected patients with diabetes
ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.
said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.
It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.
“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.
Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”
Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).
One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.
“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).
As for other diabetes management issues, Dr. Brown noted that hemoglobin A1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm3 and/or mean cell volume over 100 fL.
Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”
He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.
On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).
He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.
Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.
ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.
said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.
It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.
“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.
Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”
Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).
One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.
“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).
As for other diabetes management issues, Dr. Brown noted that hemoglobin A1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm3 and/or mean cell volume over 100 fL.
Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”
He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.
On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).
He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.
Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.
ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.
said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.
It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.
“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.
Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”
Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).
One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.
“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).
As for other diabetes management issues, Dr. Brown noted that hemoglobin A1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm3 and/or mean cell volume over 100 fL.
Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”
He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.
On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).
He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.
Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.
EXPERT ANALYSIS FROM ADA 2018
Closed-loop insulin control for T2DM is feasible in hospital setting
ORLANDO – (T2DM).
The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.
All of the subjects required subcutaneous insulin therapy.
From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).
It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.
This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.
For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.
In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).
For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).
The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.
None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.
There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)
Three patients in each group had adverse trial-related device effects.
Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.
Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.
The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.
Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.
SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018
ORLANDO – (T2DM).
The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.
All of the subjects required subcutaneous insulin therapy.
From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).
It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.
This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.
For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.
In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).
For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).
The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.
None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.
There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)
Three patients in each group had adverse trial-related device effects.
Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.
Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.
The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.
Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.
SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018
ORLANDO – (T2DM).
The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.
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For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.
All of the subjects required subcutaneous insulin therapy.
From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).
It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.
This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.
For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.
In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).
For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).
The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.
None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.
There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)
Three patients in each group had adverse trial-related device effects.
Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.
Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.
The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.
Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.
SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018
REPORTING FROM ADA 2018
Key clinical point: Use of an automated closed-loop insulin delivery system may be feasible in the noncritical hospital setting.
Major finding: In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared with 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% CI, 19-30; P less than .001).
Study details: Randomized, open-label, two-center trial of 136 inpatients with type 2 diabetes mellitus assigned to either standard subcutaneous insulin therapy or closed-loop insulin delivery for 15 days or until discharge.
Disclosures: The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission. The researchers reported no disclosures or various disclosures.
Source: Bally L et al. ADA 2018 Abstract 350-OR.
Meet the rare diabetes diagnosis that thrills patients
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
ORLANDO – Liana K. Billings, MD, an endocrinologist at the University of Chicago and the NorthShore University HealthSystem in Skokie, Ill., loves the thrill of letting patients know they have a rare kind of diabetes. “Once you do this once, you don’t want to stop,” she told colleagues in a presentation at the annual scientific sessions of the American Diabetes Association.
Yes, it’s true: There’s a diabetes diagnosis that spawns good feelings like delight and relief. The cause for celebration is a condition known as monogenetic diabetes, also known as maturity-onset diabetes of the young (MODY) if it develops after the neonatal period.
“The reason that getting a diagnosis of MODY can be a ‘good’ diagnosis is because the three most common forms of MODY have gene-specific treatments that typically improve patients’ glycemic control and are less onerous than the treatments patients were previously receiving when they were thought to have type 1 or type 2 diabetes,” explained Miriam S. Udler, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, in an interview.
Dr. Udler and Dr. Billings spoke to colleagues about monogenetic diabetes in their presentation at the ADA meeting.
Research has suggested that 1%-4% of people with diabetes have the monogenetic form, in which the condition is caused by changes in a single gene. A 2017 British study of 1,407 patients with diabetes reported that “the minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.”
The study, which tested a screening regimen, also turned up 17 new diagnoses of monogenetic diabetes among the 1,407 patients, doubling the total. The findings reflect an apparent fact about monogenetic diabetes: Physicians often don’t look for it, even though a diagnosis can be a godsend – especially for those who were previously diagnosed with type 1 or type 2 and placed on treatment regimens that are unnecessary at best and harmful at worst. (Diabetes Care. 2017 Aug;40[8]: 1017-25)
Patients with the MODY variant in the GCK gene, for example, “can generally stop all medications because they are not at risk for clinically significant complications of diabetes,” Dr. Udler said. “Patients with HNF1A and HNF4A variants can often be switched from insulin injections to ... a sulfonylurea, which is easier to take than insulin injections, and patients generally have better glycemic control after switching to pills.”
Unfortunately for doctors and patients, it can be complicated and costly to test for monogenetic diabetes. But screening tools are available to help physicians make choices about whether to launch testing in the first place, according to Dr. Udler and Dr. Billings.
There are two forms of monogenetic diabetes – neonatal diabetes, which is diagnosed by age 6-9 months, and MODY, which is typically diagnosed in those aged between 10 and 25 years, noted Dr. Billings.
Reasons to suspect MODY include early onset of diabetes (under 35 years), a family history of diabetes, a lack of obesity, and negative islet-cell antibodies, she said.
Obese patients may also have the condition: A 2017 American study of 488 overweight and obese children and adolescents diagnosed with type 2 diabetes found that 4.5% actually had monogenetic diabetes. (Genet Med. 2018 Jun;20[6]:583-90).
Once a physician suspects MODY, physicians may consult the University of Exeter’s risk calculator. It provides guidance about whether a test is a good idea. Dr. Billings cautioned, however, that the value of a calculator’s estimate of risk is not all-encompassing. “You should never use the calculator by itself as a reason to not pursue your intuition,” she said.
Dr. Udler noted that the University of Exeter calculator has important limitations, such as its reliance on specific genes, its lack of consideration of family history outside of parents, and its reliance on the experiences of white European patients.
As for tests, the University of Chicago and the University of Exeter both offer free genetic testing for neonatal diabetes, Dr. Billings said in her presentation.
Monogenetic diabetes tests in older children and adults are not free. However, Dr. Udler said the tests are often covered by insurance companies whether done for one or more genes.
At least one company offers a direct-to-consumer monogenetic diabetes test, according to Dr. Udler, but she recommended against it, especially in light of a curious online notice that says the test isn’t intended to be diagnostic. “I’m not sure what this would be useful for then,” she said.
For her part, Dr. Billings cautioned that test results may be inconclusive, and tests may offer different answers. She also recommended referring patients to genetic counseling.
Dr. Udler reported a board member/advisory panel relationship with Encompass Bioscience. Dr. Billings reported relationships with Novo Nordisk, Sanofi, and Dexcom.
EXPERT ANALYSIS FROM ADA 2018