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Fentanyl fears drive many opioid users, interviews suggest
SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”
So say opioid users who are opening up to researchers about the deadly new American drug landscape.
There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.
“When we first went into the field, there was a strong negative opinion about fentanyl. It was not wanted; it was imposed,” said Dr. Ciccarone of the University of California at San Francisco. “While there is some shift now, in which some do want or like the fentanyl, it is not strong enough to have shifted the culture. i.e., .”
But fentanyl still is rampant, often making its way to users who do not want and might be actively trying to avoid it. According to the National Institute on Drug Abuse, or NIDA, fentanyl and fentanyl analogs were linked to more than 20,000 of the more than 64,000 fatal U.S. drug overdoses in 2016.
“The risks are greater with fentanyl and not just because it is more potent than heroin,” Dr. Ciccarone said. In addition, “the form (fentanyl vs. fentanyl analogs) and purity shifts on a daily basis, and it’s mixed with heroin in varying amounts. It is these vicissitudes in fentanyl/heroin types and purities that make the street blends dangerous for overdose.”
Dr. Ciccarone and his colleagues interviewed opioid users in Baltimore; Charleston, W. Va.; Lawrence and Lowell, Mass.; and Chicago. Information about some of the interviews was published previously (Intl J Drug Policy. 2017 Aug;46;146-55).
In another study whose results were released at the CPDD conference, researchers from Dartmouth College, Hanover, N.H., interviewed 76 opioid users (91% were white, average age was 34, half were female, and almost all had a history of substance abuse treatment).
Among the other findings of the studies:
- Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
- In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
- Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”
Some say pursue fentanyl
In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”
She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”
As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
Comments from users about fentanyl
- “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
- “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”
Risk-reduction techniques embraced
- In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
- Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”
Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.
“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”
Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.
SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”
So say opioid users who are opening up to researchers about the deadly new American drug landscape.
There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.
“When we first went into the field, there was a strong negative opinion about fentanyl. It was not wanted; it was imposed,” said Dr. Ciccarone of the University of California at San Francisco. “While there is some shift now, in which some do want or like the fentanyl, it is not strong enough to have shifted the culture. i.e., .”
But fentanyl still is rampant, often making its way to users who do not want and might be actively trying to avoid it. According to the National Institute on Drug Abuse, or NIDA, fentanyl and fentanyl analogs were linked to more than 20,000 of the more than 64,000 fatal U.S. drug overdoses in 2016.
“The risks are greater with fentanyl and not just because it is more potent than heroin,” Dr. Ciccarone said. In addition, “the form (fentanyl vs. fentanyl analogs) and purity shifts on a daily basis, and it’s mixed with heroin in varying amounts. It is these vicissitudes in fentanyl/heroin types and purities that make the street blends dangerous for overdose.”
Dr. Ciccarone and his colleagues interviewed opioid users in Baltimore; Charleston, W. Va.; Lawrence and Lowell, Mass.; and Chicago. Information about some of the interviews was published previously (Intl J Drug Policy. 2017 Aug;46;146-55).
In another study whose results were released at the CPDD conference, researchers from Dartmouth College, Hanover, N.H., interviewed 76 opioid users (91% were white, average age was 34, half were female, and almost all had a history of substance abuse treatment).
Among the other findings of the studies:
- Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
- In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
- Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”
Some say pursue fentanyl
In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”
She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”
As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
Comments from users about fentanyl
- “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
- “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”
Risk-reduction techniques embraced
- In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
- Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”
Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.
“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”
Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.
SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”
So say opioid users who are opening up to researchers about the deadly new American drug landscape.
There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.
“When we first went into the field, there was a strong negative opinion about fentanyl. It was not wanted; it was imposed,” said Dr. Ciccarone of the University of California at San Francisco. “While there is some shift now, in which some do want or like the fentanyl, it is not strong enough to have shifted the culture. i.e., .”
But fentanyl still is rampant, often making its way to users who do not want and might be actively trying to avoid it. According to the National Institute on Drug Abuse, or NIDA, fentanyl and fentanyl analogs were linked to more than 20,000 of the more than 64,000 fatal U.S. drug overdoses in 2016.
“The risks are greater with fentanyl and not just because it is more potent than heroin,” Dr. Ciccarone said. In addition, “the form (fentanyl vs. fentanyl analogs) and purity shifts on a daily basis, and it’s mixed with heroin in varying amounts. It is these vicissitudes in fentanyl/heroin types and purities that make the street blends dangerous for overdose.”
Dr. Ciccarone and his colleagues interviewed opioid users in Baltimore; Charleston, W. Va.; Lawrence and Lowell, Mass.; and Chicago. Information about some of the interviews was published previously (Intl J Drug Policy. 2017 Aug;46;146-55).
In another study whose results were released at the CPDD conference, researchers from Dartmouth College, Hanover, N.H., interviewed 76 opioid users (91% were white, average age was 34, half were female, and almost all had a history of substance abuse treatment).
Among the other findings of the studies:
- Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
- In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
- Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”
Some say pursue fentanyl
In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”
She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”
As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
Comments from users about fentanyl
- “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
- “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”
Risk-reduction techniques embraced
- In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
- Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”
Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.
“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”
Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.
REPORTING FROM CPDD 2018
Daratumumab plus carfilzomib/dexamethasone effective in lenalidomide-refractory myeloma
CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.
The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.
The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.
Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”
The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.
Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.
Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.
Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.
With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.
Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.
Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.
Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.
Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.
SOURCE: Chari A et al. ASCO 2018, Abstract 8002.
CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.
The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.
The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.
Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”
The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.
Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.
Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.
Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.
With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.
Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.
Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.
Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.
Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.
SOURCE: Chari A et al. ASCO 2018, Abstract 8002.
CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.
The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.
The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.
Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”
The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.
Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.
Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.
Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.
With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.
Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.
Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.
Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.
Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.
SOURCE: Chari A et al. ASCO 2018, Abstract 8002.
REPORTING FROM ASCO 2018
Key clinical point: Daratumumab, carfilzomib, and dexamethasone (D-Kd) was safe and effective in patients with relapsed multiple myeloma, regardless of prior lenalidomide exposure.
Major finding: The 12-month rate of progression-free survival was 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.
Study details: Subgroup analysis of 85 patients in MMY1001, an open label, phase 1b study.
Disclosures: Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.
Source: Chari A et al. ASCO 2018, Abstract 8002.
Transgender men need counseling on contraceptive and reproductive choices
Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.
Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.
Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.
A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.
Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.
The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.
One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.
“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”
The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.
The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.
SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.
Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.
Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.
Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.
A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.
Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.
The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.
One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.
“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”
The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.
The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.
SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.
Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.
Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.
Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.
A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.
Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.
The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.
One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.
“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”
The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.
The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.
SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.
FROM CONTRACEPTION
Key clinical point: Transgender men need advice on reproductive and contraceptive choices.
Major finding: Half of transgender men were not asked about their fertility desires.
Study details: An online survey of 197 female-to-male transgender men.
Disclosures: The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.
Source: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.
TAVR-related stroke risk unrelated to anatomy
PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“We looked at the anatomy in great detail. I’d hoped to find a strata that was truly high risk, but there is no clear strata that is truly higher risk. So stroke remains an unpredictable event in TAVR, and in the ideal world we would use cerebroembolic protection in everyone,” said Dr. Jilaihawi, codirector of transcatheter valve therapy at New York University.
“I put it to you that, as in carotid stenting, where we routinely use cerebroembolic protection, perhaps we need to consider the same in TAVR,” the cardiologist added.
The SENTINEL trial randomized 363 patients undergoing TAVR 2:1 to the use of the Sentinel intraluminal filter device or no neuroprotection during the procedure. The use of the cerebroembolic protection device was associated with a statistically significant 63% reduction in the incidence of neurologist-adjudicated stroke within 72 hours, from 8.2% to 3.0% (J Am Coll Cardiol. 2017 Jan 31;69[4]:367-77). The device was cleared for marketing by the Food and Drug Administration in 2017 and approved by European authorities several years earlier.
A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.
“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.
Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.
He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.
There was, however, one unexpected and counterintuitive finding: The greatest stroke reduction with cerebroembolic protection was seen in patients with the least aortic valve calcium. This prompted session cochair Alain Cribier, MD, professor of medicine at the University of Rouen, France, to observe that perhaps valve repositioning is an important factor in TAVR-related strokes. After all, he noted, valve repositioning occurs more often when a patient’s valves are softer and less calcified.
“This is a very important point,” Dr. Jilaihawi responded. “I think there is an interplay between procedural aspects and the anatomy which is not completely captured in this study because we don’t know whose valve was repositioned multiple times.”
He added that the finding that TAVR-related stroke is more common in patients with less calcified aortic valves is consistent with the earlier experience in carotid stenting.
“If you look 10 years ago in the field of carotid stenting, there were a lot of analyses done which concluded that the highest-risk lesions are the least calcified lesions, even though it’s counterintuitive,” he said.
Discussant Saibal Kar, MD, director of interventional cardiac research at Cedars-Sinai Medical Center in Los Angeles, said the take-home point from the SENTINEL analysis is clear: “Cerebroembolic protection is like a seat belt: You should wear it. All patients should wear it.”
The SENTINEL trial was sponsored by Claret Medical. Dr. Jilaihawi reported receiving research grants from Abbott and Medtronic and serving as a consultant to Edwards Lifesciences and Venus Medtech.
SOURCE: Jilaihawi H. EuroPCR 2018.
PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“We looked at the anatomy in great detail. I’d hoped to find a strata that was truly high risk, but there is no clear strata that is truly higher risk. So stroke remains an unpredictable event in TAVR, and in the ideal world we would use cerebroembolic protection in everyone,” said Dr. Jilaihawi, codirector of transcatheter valve therapy at New York University.
“I put it to you that, as in carotid stenting, where we routinely use cerebroembolic protection, perhaps we need to consider the same in TAVR,” the cardiologist added.
The SENTINEL trial randomized 363 patients undergoing TAVR 2:1 to the use of the Sentinel intraluminal filter device or no neuroprotection during the procedure. The use of the cerebroembolic protection device was associated with a statistically significant 63% reduction in the incidence of neurologist-adjudicated stroke within 72 hours, from 8.2% to 3.0% (J Am Coll Cardiol. 2017 Jan 31;69[4]:367-77). The device was cleared for marketing by the Food and Drug Administration in 2017 and approved by European authorities several years earlier.
A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.
“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.
Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.
He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.
There was, however, one unexpected and counterintuitive finding: The greatest stroke reduction with cerebroembolic protection was seen in patients with the least aortic valve calcium. This prompted session cochair Alain Cribier, MD, professor of medicine at the University of Rouen, France, to observe that perhaps valve repositioning is an important factor in TAVR-related strokes. After all, he noted, valve repositioning occurs more often when a patient’s valves are softer and less calcified.
“This is a very important point,” Dr. Jilaihawi responded. “I think there is an interplay between procedural aspects and the anatomy which is not completely captured in this study because we don’t know whose valve was repositioned multiple times.”
He added that the finding that TAVR-related stroke is more common in patients with less calcified aortic valves is consistent with the earlier experience in carotid stenting.
“If you look 10 years ago in the field of carotid stenting, there were a lot of analyses done which concluded that the highest-risk lesions are the least calcified lesions, even though it’s counterintuitive,” he said.
Discussant Saibal Kar, MD, director of interventional cardiac research at Cedars-Sinai Medical Center in Los Angeles, said the take-home point from the SENTINEL analysis is clear: “Cerebroembolic protection is like a seat belt: You should wear it. All patients should wear it.”
The SENTINEL trial was sponsored by Claret Medical. Dr. Jilaihawi reported receiving research grants from Abbott and Medtronic and serving as a consultant to Edwards Lifesciences and Venus Medtech.
SOURCE: Jilaihawi H. EuroPCR 2018.
PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“We looked at the anatomy in great detail. I’d hoped to find a strata that was truly high risk, but there is no clear strata that is truly higher risk. So stroke remains an unpredictable event in TAVR, and in the ideal world we would use cerebroembolic protection in everyone,” said Dr. Jilaihawi, codirector of transcatheter valve therapy at New York University.
“I put it to you that, as in carotid stenting, where we routinely use cerebroembolic protection, perhaps we need to consider the same in TAVR,” the cardiologist added.
The SENTINEL trial randomized 363 patients undergoing TAVR 2:1 to the use of the Sentinel intraluminal filter device or no neuroprotection during the procedure. The use of the cerebroembolic protection device was associated with a statistically significant 63% reduction in the incidence of neurologist-adjudicated stroke within 72 hours, from 8.2% to 3.0% (J Am Coll Cardiol. 2017 Jan 31;69[4]:367-77). The device was cleared for marketing by the Food and Drug Administration in 2017 and approved by European authorities several years earlier.
A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.
“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.
Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.
He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.
There was, however, one unexpected and counterintuitive finding: The greatest stroke reduction with cerebroembolic protection was seen in patients with the least aortic valve calcium. This prompted session cochair Alain Cribier, MD, professor of medicine at the University of Rouen, France, to observe that perhaps valve repositioning is an important factor in TAVR-related strokes. After all, he noted, valve repositioning occurs more often when a patient’s valves are softer and less calcified.
“This is a very important point,” Dr. Jilaihawi responded. “I think there is an interplay between procedural aspects and the anatomy which is not completely captured in this study because we don’t know whose valve was repositioned multiple times.”
He added that the finding that TAVR-related stroke is more common in patients with less calcified aortic valves is consistent with the earlier experience in carotid stenting.
“If you look 10 years ago in the field of carotid stenting, there were a lot of analyses done which concluded that the highest-risk lesions are the least calcified lesions, even though it’s counterintuitive,” he said.
Discussant Saibal Kar, MD, director of interventional cardiac research at Cedars-Sinai Medical Center in Los Angeles, said the take-home point from the SENTINEL analysis is clear: “Cerebroembolic protection is like a seat belt: You should wear it. All patients should wear it.”
The SENTINEL trial was sponsored by Claret Medical. Dr. Jilaihawi reported receiving research grants from Abbott and Medtronic and serving as a consultant to Edwards Lifesciences and Venus Medtech.
SOURCE: Jilaihawi H. EuroPCR 2018.
REPORTING FROM EUROPCR 2018
Key clinical point: .
Major finding: Neither aortic arch type, root angulation, nor calcium burden identifies a subgroup of TAVR patients at higher stroke risk.
Study details: The SENTINEL trial randomized 363 TAVR patients 2:1 to the use of a cerebroembolic protection device or no neuroprotection during the procedure.
Disclosures: The SENTINEL trial was sponsored by Claret Medical. The presenter reported having no financial conflicts of interest.
Source: Jilaihawi H. EuroPCR 2018.
Disparities found in access to medication treatment for OUDs
The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.
“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.
Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.
The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.
The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.
The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)
Those trends changed by 2009. Compared with individuals living in all other types of counties, those living in counties with a lower proportion of black residents and a low poverty rate were much more likely to receive medication treatment. A similar pattern was seen among populations with a lower proportion of Hispanic residents and a low poverty rate, compared with communities with high numbers of Hispanics and not low poverty rate.
Dr. Stein and his colleagues cited several limitations. First, because the study analyzed Medicaid enrollees, it is not known how the findings might translate to uninsured or commercially insured patients. Another limitation is that the study data analyzed patients until 2009, making it difficult to generalize the findings to the population today. Finally, the researchers used a population-based approach.
Nevertheless, they said, the study advances understanding of the impact of buprenorphine on medication treatment among patients who receive Medicaid.
“At a time of intensive policymaker and regulatory efforts to increase [medication treatment] availability, of suffering from these disorders,” Dr. Stein and his colleagues wrote.
The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.
SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.
The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.
“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.
Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.
The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.
The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.
The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)
Those trends changed by 2009. Compared with individuals living in all other types of counties, those living in counties with a lower proportion of black residents and a low poverty rate were much more likely to receive medication treatment. A similar pattern was seen among populations with a lower proportion of Hispanic residents and a low poverty rate, compared with communities with high numbers of Hispanics and not low poverty rate.
Dr. Stein and his colleagues cited several limitations. First, because the study analyzed Medicaid enrollees, it is not known how the findings might translate to uninsured or commercially insured patients. Another limitation is that the study data analyzed patients until 2009, making it difficult to generalize the findings to the population today. Finally, the researchers used a population-based approach.
Nevertheless, they said, the study advances understanding of the impact of buprenorphine on medication treatment among patients who receive Medicaid.
“At a time of intensive policymaker and regulatory efforts to increase [medication treatment] availability, of suffering from these disorders,” Dr. Stein and his colleagues wrote.
The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.
SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.
The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.
“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.
Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.
The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.
The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.
The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)
Those trends changed by 2009. Compared with individuals living in all other types of counties, those living in counties with a lower proportion of black residents and a low poverty rate were much more likely to receive medication treatment. A similar pattern was seen among populations with a lower proportion of Hispanic residents and a low poverty rate, compared with communities with high numbers of Hispanics and not low poverty rate.
Dr. Stein and his colleagues cited several limitations. First, because the study analyzed Medicaid enrollees, it is not known how the findings might translate to uninsured or commercially insured patients. Another limitation is that the study data analyzed patients until 2009, making it difficult to generalize the findings to the population today. Finally, the researchers used a population-based approach.
Nevertheless, they said, the study advances understanding of the impact of buprenorphine on medication treatment among patients who receive Medicaid.
“At a time of intensive policymaker and regulatory efforts to increase [medication treatment] availability, of suffering from these disorders,” Dr. Stein and his colleagues wrote.
The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.
SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.
FROM SUBSTANCE ABUSE
Key clinical point: Medication treatment access for opioid use disorders varies greatly among Medicaid enrollees.
Major finding: Residents of counties with a lower proportion of black residents and a low poverty rate are much more likely to receive medication treatment.
Study details: An analysis of Medicaid claims from 2002 to 2009 from 14 states representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees.
Disclosures: This study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.
Source: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.
FDA reverses warning on LABA-containing asthma medications
The combination a by 17%, without increasing the risk of asthma-related intubation or death.
An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.
“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.
The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.
In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.
“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.
The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.
Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.
Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.
However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.
The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.
“… Our data provide support for the treatment guidelines of both the Global Initiative for Asthma and the Expert Panel Report 3 of the National Asthma Education and Prevention Program, which recommend the use of a low-dose glucocorticoid (step 3) and a medium-dose glucocorticoid (step 4), plus a LABA, with the caution that LABAs should not be used as monotherapy in asthma; the convenience and safety of a combination inhaler is a likely plus,” the committee wrote. “Finally, our combined analysis provides strong evidence to support the recent FDA decision to remove the boxed safety warning for combination therapy with a LABA plus an inhaled glucocorticoid for asthma treatment.”
Dr. Busse disclosed financial relationships with a number of pharmaceutical companies, including Novartis, but noted that none of them were relevant to this work.
SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.
It takes a lot for the FDA to remove a boxed warning on a product, but the data generated by these four manufacturer-led trials of long-acting beta agonists and inhaled corticosteroid combination therapy warrant the regulatory reversal, Sally Seymour, MD, and her colleagues wrote in an accompanying editorial.
“Each completed trial met the prespecified objective and demonstrated noninferiority of combination products to inhaled corticosteroids alone with respect to the composite endpoint of asthma-related death, intubation, or hospitalization.
The majority of events were asthma-related hospitalizations; there were five intubations and deaths overall,” Dr. Seymour and her colleagues wrote.
All of the studies met their primary safety objective, and faced with this – and the consistency of the results among the studies – the path was clear.
“In addition, the observed reduction in asthma exacerbations that required systemic corticosteroids demonstrates a benefit associated with combination products. On the basis of this strong and consistent evidence, we opted to remove the boxed warning right away, without convening an FDA advisory committee meeting.”
There will always be areas of uncertainty, however.
“Admittedly, the results from these trials cannot answer all questions regarding the safety of LABAs. Some uncertainties remain, and we cannot conclude that there is no increase in risk associated with combination products containing an inhaled corticosteroid and a LABA as compared with inhaled corticosteroids alone. Although the trials found that combination therapy reduces the rate of exacerbations that require the administration of systemic corticosteroids, none of them showed a decrease in asthma-related hospitalizations. People with life-threatening asthma were excluded because of safety and ethical concerns, so we don’t know whether the results can be generalized to these patients.”
Nevertheless, the evidence in favor of combination therapy was clear and compelling enough to convince a national regulatory agency to change a stance on safety.
Dr. Seymour is the acting director of the FDA’s Division of Pulmonary, Allergy, & Rheumatology Products.
It takes a lot for the FDA to remove a boxed warning on a product, but the data generated by these four manufacturer-led trials of long-acting beta agonists and inhaled corticosteroid combination therapy warrant the regulatory reversal, Sally Seymour, MD, and her colleagues wrote in an accompanying editorial.
“Each completed trial met the prespecified objective and demonstrated noninferiority of combination products to inhaled corticosteroids alone with respect to the composite endpoint of asthma-related death, intubation, or hospitalization.
The majority of events were asthma-related hospitalizations; there were five intubations and deaths overall,” Dr. Seymour and her colleagues wrote.
All of the studies met their primary safety objective, and faced with this – and the consistency of the results among the studies – the path was clear.
“In addition, the observed reduction in asthma exacerbations that required systemic corticosteroids demonstrates a benefit associated with combination products. On the basis of this strong and consistent evidence, we opted to remove the boxed warning right away, without convening an FDA advisory committee meeting.”
There will always be areas of uncertainty, however.
“Admittedly, the results from these trials cannot answer all questions regarding the safety of LABAs. Some uncertainties remain, and we cannot conclude that there is no increase in risk associated with combination products containing an inhaled corticosteroid and a LABA as compared with inhaled corticosteroids alone. Although the trials found that combination therapy reduces the rate of exacerbations that require the administration of systemic corticosteroids, none of them showed a decrease in asthma-related hospitalizations. People with life-threatening asthma were excluded because of safety and ethical concerns, so we don’t know whether the results can be generalized to these patients.”
Nevertheless, the evidence in favor of combination therapy was clear and compelling enough to convince a national regulatory agency to change a stance on safety.
Dr. Seymour is the acting director of the FDA’s Division of Pulmonary, Allergy, & Rheumatology Products.
It takes a lot for the FDA to remove a boxed warning on a product, but the data generated by these four manufacturer-led trials of long-acting beta agonists and inhaled corticosteroid combination therapy warrant the regulatory reversal, Sally Seymour, MD, and her colleagues wrote in an accompanying editorial.
“Each completed trial met the prespecified objective and demonstrated noninferiority of combination products to inhaled corticosteroids alone with respect to the composite endpoint of asthma-related death, intubation, or hospitalization.
The majority of events were asthma-related hospitalizations; there were five intubations and deaths overall,” Dr. Seymour and her colleagues wrote.
All of the studies met their primary safety objective, and faced with this – and the consistency of the results among the studies – the path was clear.
“In addition, the observed reduction in asthma exacerbations that required systemic corticosteroids demonstrates a benefit associated with combination products. On the basis of this strong and consistent evidence, we opted to remove the boxed warning right away, without convening an FDA advisory committee meeting.”
There will always be areas of uncertainty, however.
“Admittedly, the results from these trials cannot answer all questions regarding the safety of LABAs. Some uncertainties remain, and we cannot conclude that there is no increase in risk associated with combination products containing an inhaled corticosteroid and a LABA as compared with inhaled corticosteroids alone. Although the trials found that combination therapy reduces the rate of exacerbations that require the administration of systemic corticosteroids, none of them showed a decrease in asthma-related hospitalizations. People with life-threatening asthma were excluded because of safety and ethical concerns, so we don’t know whether the results can be generalized to these patients.”
Nevertheless, the evidence in favor of combination therapy was clear and compelling enough to convince a national regulatory agency to change a stance on safety.
Dr. Seymour is the acting director of the FDA’s Division of Pulmonary, Allergy, & Rheumatology Products.
The combination a by 17%, without increasing the risk of asthma-related intubation or death.
An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.
“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.
The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.
In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.
“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.
The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.
Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.
Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.
However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.
The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.
“… Our data provide support for the treatment guidelines of both the Global Initiative for Asthma and the Expert Panel Report 3 of the National Asthma Education and Prevention Program, which recommend the use of a low-dose glucocorticoid (step 3) and a medium-dose glucocorticoid (step 4), plus a LABA, with the caution that LABAs should not be used as monotherapy in asthma; the convenience and safety of a combination inhaler is a likely plus,” the committee wrote. “Finally, our combined analysis provides strong evidence to support the recent FDA decision to remove the boxed safety warning for combination therapy with a LABA plus an inhaled glucocorticoid for asthma treatment.”
Dr. Busse disclosed financial relationships with a number of pharmaceutical companies, including Novartis, but noted that none of them were relevant to this work.
SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.
The combination a by 17%, without increasing the risk of asthma-related intubation or death.
An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.
“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.
The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.
In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.
“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.
The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.
Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.
Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.
However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.
The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.
“… Our data provide support for the treatment guidelines of both the Global Initiative for Asthma and the Expert Panel Report 3 of the National Asthma Education and Prevention Program, which recommend the use of a low-dose glucocorticoid (step 3) and a medium-dose glucocorticoid (step 4), plus a LABA, with the caution that LABAs should not be used as monotherapy in asthma; the convenience and safety of a combination inhaler is a likely plus,” the committee wrote. “Finally, our combined analysis provides strong evidence to support the recent FDA decision to remove the boxed safety warning for combination therapy with a LABA plus an inhaled glucocorticoid for asthma treatment.”
Dr. Busse disclosed financial relationships with a number of pharmaceutical companies, including Novartis, but noted that none of them were relevant to this work.
SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Combination LABA/inhaled glucocorticoid products appear safe for patients with asthma.
Major finding: The products reduced the risk of an asthma exacerbation by 17%, without increasing the risk of a serious adverse outcome.
Study details: The four randomized studies comprised more than 13,000 patients.
Disclosures: The studies were sponsored by AstraZeneca, GlaxoSmithKline, Merck, and Novartis. Dr. Busse disclosed a financial relationship with Novartis, but said it was not relevant to this work.
Source: Busse WW. N Engl J Med. 2018;78:2497-505.
Death rates rising for 10- to 19-year-olds
Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.
The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.
The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.
“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.
SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.
Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.
The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.
The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.
“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.
SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.
Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.
The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.
The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.
“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.
SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.
FROM NATIONAL VITAL STATISTICS REPORTS
July 2018 Question 2
Q2. Correct Answer: A
Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.
References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.
Q2. Correct Answer: A
Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.
References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.
Q2. Correct Answer: A
Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.
References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.
A 54-year-old woman presents for management of moderately-severe ileocolonic Crohn’s disease. She has a strong family history of multiple sclerosis and recently noted some tingling in her toes for which she is undergoing neurologic evaluation. She has had two small basal cell carcinomas removed from her cheek in the last year. She received the BCG vaccine as a child and had a positive PPD skin test within the last year. Laboratory evaluation reveals HBsAg negative, anti-HBs positive, and anti-HBc positive; JC virus antibody is positive.
July 2018 Question 1
Q1. Correct Answer: A
Rationale
This patient has an idiopathic, non-NSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers.
References
1. Wong G.L.H., Wong V.W.S. Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31.
2. Laine L. Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107[3]:345-60.
Q1. Correct Answer: A
Rationale
This patient has an idiopathic, non-NSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers.
References
1. Wong G.L.H., Wong V.W.S. Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31.
2. Laine L. Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107[3]:345-60.
Q1. Correct Answer: A
Rationale
This patient has an idiopathic, non-NSAID, non-H. pylori-associated ulcer and should be on daily PPI indefinitely. These patients have a high rate of recurrent bleeding (42%) and mortality when followed prospectively without being on antisecretory therapy. Although no randomized trials have assessed the benefit of medical cotherapy in this population, antiulcer therapy seems to reduce recurrent idiopathic ulcers.
References
1. Wong G.L.H., Wong V.W.S. Chan Y., et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137:525-31.
2. Laine L. Jensen D.M. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107[3]:345-60.
A 60-year-old woman is admitted to the hospital with an upper GI bleed and found to have a gastric ulcer. Biopsies from the ulcer show no malignancy. Gastric biopsies reveal no Helicobacter pylori and stool antigen for H. pylori is also negative. The patient denies any NSAID use. She is discharged home on twice-daily PPI. Two months later, she returns for a follow-up endoscopy, and the ulcer has healed.
Navigating travel with diabetes
Travel, once reserved for wealthy vacationers and high-level executives, has become a regular experience for many people. The US Travel and Tourism Overview reported that US domestic travel climbed to more than 2.25 billion person-trips in 2017.1 The US Centers for Disease Control and Prevention (CDC) and the US Travel Association suggest that, based on this frequency and the known rate of diabetes, 17 million people with diabetes travel annually for leisure and 5.6 million for business, and these numbers are expected to increase.2
It stands to reason that as the number of people who travel continues to increase, so too will the number of patients with diabetes seeking medical travel advice. Despite resources available to travelers with diabetes, researchers at the 2016 meeting of the American Diabetes Association noted that only 30% of patients with diabetes who responded to a survey reported being satisfied with the resources available to help them manage their diabetes while traveling.2 This article discusses how clinicians can help patients manage their diabetes while traveling, address common travel questions, and prepare patients for emergencies that may arise while traveling.
PRE-TRIP PREPARATION
Provider visit before travel: Checking the bases
Advise patients to schedule an appointment 4 to 6 weeks before their trip.3 At this appointment, give the patient a healthcare provider travel letter (Figure 1) and prescriptions that the patient can hand-carry en route.3 The provider letter should state that the patient has diabetes and should list all supplies the patient needs. The letter should also include specific medications used by the patient and the devices that deliver these medications, eg, Humalog insulin and U-100 syringes4 to administer insulin, as well as any food and medication allergies.
Prescriptions should be written for patients to use in the event of an emergency during travel. Prescriptions for diabetes medications should be written with generic names to minimize confusion for those traveling internationally. Additionally, all prescriptions should provide enough medication to last throughout the trip.4
Advise patients that rules for filling prescriptions may vary between states and countries.3 Also, the strength of insulin may vary between the United States and other countries. Patients should understand that if they fill their insulin prescription in a foreign country, they may need to purchase new syringes to match the insulin dose. For example, if patients use U-100 syringes and purchase U-40 insulin, they will need to buy U-40 syringes or risk taking too little of a dose.
Remind patients that prescriptions are not necessary for all diabetes supplies but are essential for coverage by insurance companies. Blood glucose testing supplies, ketone strips, and glucose tablets may be purchased in a pharmacy without a prescription. Human insulin may also be purchased over the counter. However, oral medications, glucagon, and analog insulins require a prescription. We suggest that patients who travel have their prescriptions on file at a chain pharmacy rather than an independent one. If they are in the United States, they can go to any branch of the chain pharmacy and easily fill a prescription.
Work with the patient to compile a separate document that details the medication dosing, correction-scale instructions, carbohydrate-to-insulin ratios, and pump settings (basal rates, insulin sensitivity, active insulin time).4 Patients who use an insulin pump should record all pump settings in the event that they need to convert to insulin injections during travel.4 We suggest that all patients with an insulin pump have an alternate insulin method (eg, pens, vials) and that they carry this with them along with basal insulin in case the pump fails. This level of preparation empowers the patient to assume responsibility for his or her own care if a healthcare provider is not available during travel.
Like all travelers, patients with diabetes should confirm that their immunizations are up to date. Encourage patients to the CDC’s page (wwwnc.cdc.gov/travel) to check the list of vaccines necessary for their region of travel.4,5 Many special immunizations can be acquired only from a public health department and not from a clinician’s office.
Additionally, depending on the region of travel, prescribing antibiotics or antidiarrheal medications may be necessary to ensure patient safety and comfort. We also recommend that patients with type 1 diabetes obtain a supply of antibiotics and antidiarrheals because they can become sick quickly.
Packing with diabetes: Double is better
The American Diabetes Association recommends that patients pack at least twice the medication and blood-testing supplies they anticipate needing.3 Reinforce to patients the need to pack all medications and supplies in their carry-on bag and to keep this bag in their possession at all times to avoid damage, loss, and extreme changes in temperature and air pressure, which can adversely affect the activity and stability of insulin.
Ask patients about the activities they plan to participate in and how many days they will be traveling, and then recommend shoes that will encourage appropriate foot care.4 Patients with diabetes should choose comfort over style when selecting footwear. All new shoes should be purchased and “broken in” 2 to 3 weeks before the trip. Alternating shoes decreases the risk of blisters and calluses.4
Emergency abroad: Planning to be prepared
It is crucial to counsel patients on how to respond in an emergency.
Encourage patients with diabetes, especially those who use insulin, to obtain a medical identification bracelet, necklace, or in some cases, a tattoo, that states they use insulin and discloses any allergies.3 This ensures that emergency medical personnel will be aware of the patient’s condition when providing care. Also suggest that your patients have emergency contact information available on their person and their cell phone to expedite assistance in an emergency (Table 2).
Urge patients to determine prior to their departure if their health coverage will change once they leave the state or the country. Some insurance companies require patients to go to a specific healthcare system while others regulate the amount of time a patient can be in the hospital before being transferred home. It is important for patients to be aware of these terms in the event of hospitalization.4 Travel insurance should be considered for international travel.
AIRPORT SECURITY: WHAT TO EXPECT WITH DIABETES
The American Diabetes Association works with the US Transportation Security Administration (TSA) to ensure that passengers with diabetes have access to supplies. Travelers with diabetes are allowed to apply for an optional disability notification card, which discreetly informs officers that the passenger has a condition or device that may affect screening procedures.6
The TSA suggests that, before going through airport screening, patients with diabetes separate their diabetes supplies from their luggage and declare all items.6 Including prescription labels for medications and medical devices helps speed up the security process. Advise patients to carry glucose tablets and other solid foods for treating hypoglycemia when passing through airport security checkpoints.7
Since 2016, the TSA has allowed all diabetes-related supplies, medications, and equipment, including liquids and devices, through security after they have been screened by the x-ray scanner or by hand.7 People with diabetes are allowed to carry insulin and other liquid medications in amounts greater than 3.4 ounces (100 mLs) through airport security checkpoints.
Insulin can pass safely through x-ray scanners, but if patients are concerned, they may request that their insulin be inspected by hand.7 Patients must inform airport security of this decision before the screening process begins. A hand inspection may include swabbing for explosives.
Patients with an insulin pump and a continuous glucose monitoring device may feel uncomfortable during x-ray screening and special security screenings. Remind patients that it is TSA policy that patients do not need to disconnect their devices and can request screening by pat-down rather than x-ray scanner.6 It is the responsibility of the patient to research whether the pump can pass through x-ray scanners.
All patients have the right to request a pat-down and can opt out of passing through the x-ray scanner.6 However, patients need to inform officers about a pump before screening and must understand that the pump may be subject to further inspection. Usually, this additional inspection includes swabbing the patient’s hands to check for explosive material and a simple pat-down of the insulin pump.7
IN-FLIGHT TIPS
Time zones and insulin dosing
Diabetes management is often based on a 24-hour medication schedule. Travel can disrupt this schedule, making it challenging for patients to determine the appropriate medication adjustments. With some assistance, the patient can determine the best course of action based on the direction of travel and the number of time zones crossed.
According to Chandran and Edelman,7 medication adjustments are needed only when the patient is traveling east or west, not north or south. As time zones change, day length changes and, consequently, so does the 24-hour regimen many patients follow. As a general rule, traveling east results in a shortened day, requiring a potential reduction in insulin, while traveling west results in a longer day, possibly requiring an increase in insulin dose.7 However, this is a guideline and may not be applicable to all patients.7
Advise patients to follow local time to administer medications beginning the morning after arrival.7 It is not uncommon, due to changes in meal schedules and dosing, for patients to experience hyperglycemia during travel. They should be prepared to correct this if necessary.
Patients using insulin injections should plan to adjust to the new time zone as soon as possible. If the time change is only 1 or 2 hours, they should take their medications before departure according to their normal home time.7 Upon arrival, they should resume their insulin regimen based on the local time.
Westward travel. If the patient is traveling west with a time change of 3 or more hours, additional changes may be necessary. Advise patients to take their insulin according to their normal home time before departure. The change in dosing and schedule will depend largely on current glucose control, time of travel, and availability of food and glucose during travel. Encourage patients to discuss these matters with you in advance of any long travel.
Eastward travel. When the patient is traveling east with a time change greater than 3 hours, the day will be consequently shortened. On the day of travel, patients should take their morning dose according to home time. If they are concerned about hypoglycemia, suggest that they decrease the dose by 10%.6 On arrival, they should adhere to the new time zone and base insulin dosing on local time.
Advice for insulin pump users. Patients with an insulin pump need make only minimal changes to their dosing schedule. They should continue their routine of basal and bolus doses and change the time on their insulin pump to local time when they arrive. Insulin pump users should bring insulin and syringes as backup; in the event of pump malfunction, the patient should continue to use the same amount of bolus insulin to correct glucose readings and to cover meals.7 As for the basal dose, patients can administer a once-daily injection of long-acting insulin, which can be calculated from their pump or accessed from the list they created as part of their pre-travel preparation.7
Advice for patients on oral diabetes medications
If a patient is taking an oral medication, it is less crucial to adhere to a time schedule. In fact, in some cases it may be preferable to skip a dose and risk slight hyperglycemia for a few hours rather than take medication too close in time and risk hypoglycemia.7
Remind patients to anticipate a change in their oral medication regimen if they travel farther than 5 time zones.7 Encourage patients to research time changes and discuss the necessary changes in medication dosage on the day of travel as well as the specific aspects of their trip. A time-zone converter can be found at www.timeanddate.com.8
WHAT TO EXPECT WHILE ON LAND
Insulin 101
Storing insulin at the appropriate temperature may be a concern. Insulin should be kept between 40°F and 86°F (4°C–30°C).4 Remind patients to carry their insulin with them at all times and to not store it in a car glove compartment or backpack where it can be exposed to excessive sun. The Frio cold pack (ReadyCare, Walnut Creek, CA) is a helpful alternative to refrigeration and can be used to cool insulin when hiking or participating in activities where insulin can overheat. These cooling gel packs are activated when exposed to cold water for 5 to 7 minutes5 and are reusable.
Alert patients that insulin names and concentrations may vary among countries. Most insulins are U-100 concentration, which means that for every 1 mL of liquid there are 100 units of insulin. This is the standard insulin concentration used in the United States. There are U-200, U-300, and U-500 insulins as well. In Europe, the standard concentration is U-40 insulin. Syringe sizes are designed to accommodate either U-100 or U-40 insulin. Review these differences with patients and explain the consequences of mixing insulin concentration with syringes of different sizes. Figure 2 shows how to calculate equivalent doses.
Resort tips: Food, drinks, and excursions
A large component of travel is indulging in local cuisine. Patients with diabetes need to be aware of how different foods can affect their diabetes control. Encourage them to research the foods common to the local cuisine. Websites such as Calorie King, MyFitnessPal, Lose it!, and Nutrition Data can help identify the caloric and nutritional makeup of foods.9
Advise patients to actively monitor how their blood glucose is affected by new foods by checking blood glucose levels before and after each meal.9 Opting for vegetables and protein sources minimizes glucose fluctuations. Remind patients that drinks at resorts may contain more sugar than advertised. Patients should continue to manage their blood glucose by checking levels and by making appropriate insulin adjustments based on the readings. We often advise patients to pack a jar of peanut butter when traveling to ensure a ready source of protein.
Patients who plan to participate in physically challenging activities while travelling should inform all relevant members of the activity staff of their condition. In case of an emergency, hotel staff and guides will be better equipped to help with situations such as hypoglycemia. As noted above, patients should always carry snacks and supplies to treat hypoglycemia in case no alternative food options are available during an excursion. Also, warn patients to avoid walking barefoot. Water shoes are a good alternative to protect feet from cuts and sores.
Patients should inquire about the safety of high-elevation activities. With many glucose meters, every 1,000 feet of elevation results in a 1% to 2% underestimation of blood glucose,10 which could result in an inaccurate reading. If high-altitude activities are planned, advise patients to bring multiple meters to cross-check glucose readings in cases where inaccuracies (due to elevation) are possible.
- US Travel Association. US travel and tourism overview. www.ustravel.org/system/files/media_root/document/Research_Fact-Sheet_US-Travel-and-Tourism-Overview.pdf. Accessed June 14, 2018.
- Brunk D. Long haul travel turbulent for many with type 1 diabetes. Clinical Endocrinology News 2016. www.mdedge.com/clinicalendocrinologynews/article/109866/diabetes/long-haul-travel-turbulent-many-type-1-diabetes. Accessed June 14, 2018.
- American Diabetes Association. When you travel. www.diabetes.org/living-with-diabetes/treatment-and-care/when-you-travel.html?utm_source=DSH_BLOG&utm_medium=BlogPost&utm_content=051514-travel&utm_campaign=CON. Accessed June 14, 2018.
- Kruger DF. The Diabetes Travel Guide. How to travel with diabetes-anywhere in the world. Arlington, VA: American Diabetes Association; 2000.
- Centers for Disease Control and Prevention. Travelers’ health. wwwnc.cdc.gov/travel/. Accessed June 14, 2018.
- American Diabetes Association. What special concerns may arise? www.diabetes.org/living-with-diabetes/know-your-rights/discrimination/public-accommodations/air-travel-and-diabetes/what-special-concerns-may.html. Accessed June 14, 2018.
- Chandran M, Edelman SV. Have insulin, will fly: diabetes management during air travel and time zone adjustment strategies. Clinical Diabetes 2003; 21(2):82–85. doi:10.2337/diaclin.21.2.82
- Time and Date AS. Time zone converter. timeanddate.com. Accessed March 19, 2018.
- Joslin Diabetes Center. Diabetes and travel—10 tips for a safe trip. www.joslin.org/info/diabetes_and_travel_10_tips_for_a_safe_trip.html. Accessed June 14, 2018.
- Jendle J, Adolfsson P. Impact of high altitudes on glucose control. J Diabetes Sci Technol 2011; 5(6):1621–1622. doi:10.1177/193229681100500642
Travel, once reserved for wealthy vacationers and high-level executives, has become a regular experience for many people. The US Travel and Tourism Overview reported that US domestic travel climbed to more than 2.25 billion person-trips in 2017.1 The US Centers for Disease Control and Prevention (CDC) and the US Travel Association suggest that, based on this frequency and the known rate of diabetes, 17 million people with diabetes travel annually for leisure and 5.6 million for business, and these numbers are expected to increase.2
It stands to reason that as the number of people who travel continues to increase, so too will the number of patients with diabetes seeking medical travel advice. Despite resources available to travelers with diabetes, researchers at the 2016 meeting of the American Diabetes Association noted that only 30% of patients with diabetes who responded to a survey reported being satisfied with the resources available to help them manage their diabetes while traveling.2 This article discusses how clinicians can help patients manage their diabetes while traveling, address common travel questions, and prepare patients for emergencies that may arise while traveling.
PRE-TRIP PREPARATION
Provider visit before travel: Checking the bases
Advise patients to schedule an appointment 4 to 6 weeks before their trip.3 At this appointment, give the patient a healthcare provider travel letter (Figure 1) and prescriptions that the patient can hand-carry en route.3 The provider letter should state that the patient has diabetes and should list all supplies the patient needs. The letter should also include specific medications used by the patient and the devices that deliver these medications, eg, Humalog insulin and U-100 syringes4 to administer insulin, as well as any food and medication allergies.
Prescriptions should be written for patients to use in the event of an emergency during travel. Prescriptions for diabetes medications should be written with generic names to minimize confusion for those traveling internationally. Additionally, all prescriptions should provide enough medication to last throughout the trip.4
Advise patients that rules for filling prescriptions may vary between states and countries.3 Also, the strength of insulin may vary between the United States and other countries. Patients should understand that if they fill their insulin prescription in a foreign country, they may need to purchase new syringes to match the insulin dose. For example, if patients use U-100 syringes and purchase U-40 insulin, they will need to buy U-40 syringes or risk taking too little of a dose.
Remind patients that prescriptions are not necessary for all diabetes supplies but are essential for coverage by insurance companies. Blood glucose testing supplies, ketone strips, and glucose tablets may be purchased in a pharmacy without a prescription. Human insulin may also be purchased over the counter. However, oral medications, glucagon, and analog insulins require a prescription. We suggest that patients who travel have their prescriptions on file at a chain pharmacy rather than an independent one. If they are in the United States, they can go to any branch of the chain pharmacy and easily fill a prescription.
Work with the patient to compile a separate document that details the medication dosing, correction-scale instructions, carbohydrate-to-insulin ratios, and pump settings (basal rates, insulin sensitivity, active insulin time).4 Patients who use an insulin pump should record all pump settings in the event that they need to convert to insulin injections during travel.4 We suggest that all patients with an insulin pump have an alternate insulin method (eg, pens, vials) and that they carry this with them along with basal insulin in case the pump fails. This level of preparation empowers the patient to assume responsibility for his or her own care if a healthcare provider is not available during travel.
Like all travelers, patients with diabetes should confirm that their immunizations are up to date. Encourage patients to the CDC’s page (wwwnc.cdc.gov/travel) to check the list of vaccines necessary for their region of travel.4,5 Many special immunizations can be acquired only from a public health department and not from a clinician’s office.
Additionally, depending on the region of travel, prescribing antibiotics or antidiarrheal medications may be necessary to ensure patient safety and comfort. We also recommend that patients with type 1 diabetes obtain a supply of antibiotics and antidiarrheals because they can become sick quickly.
Packing with diabetes: Double is better
The American Diabetes Association recommends that patients pack at least twice the medication and blood-testing supplies they anticipate needing.3 Reinforce to patients the need to pack all medications and supplies in their carry-on bag and to keep this bag in their possession at all times to avoid damage, loss, and extreme changes in temperature and air pressure, which can adversely affect the activity and stability of insulin.
Ask patients about the activities they plan to participate in and how many days they will be traveling, and then recommend shoes that will encourage appropriate foot care.4 Patients with diabetes should choose comfort over style when selecting footwear. All new shoes should be purchased and “broken in” 2 to 3 weeks before the trip. Alternating shoes decreases the risk of blisters and calluses.4
Emergency abroad: Planning to be prepared
It is crucial to counsel patients on how to respond in an emergency.
Encourage patients with diabetes, especially those who use insulin, to obtain a medical identification bracelet, necklace, or in some cases, a tattoo, that states they use insulin and discloses any allergies.3 This ensures that emergency medical personnel will be aware of the patient’s condition when providing care. Also suggest that your patients have emergency contact information available on their person and their cell phone to expedite assistance in an emergency (Table 2).
Urge patients to determine prior to their departure if their health coverage will change once they leave the state or the country. Some insurance companies require patients to go to a specific healthcare system while others regulate the amount of time a patient can be in the hospital before being transferred home. It is important for patients to be aware of these terms in the event of hospitalization.4 Travel insurance should be considered for international travel.
AIRPORT SECURITY: WHAT TO EXPECT WITH DIABETES
The American Diabetes Association works with the US Transportation Security Administration (TSA) to ensure that passengers with diabetes have access to supplies. Travelers with diabetes are allowed to apply for an optional disability notification card, which discreetly informs officers that the passenger has a condition or device that may affect screening procedures.6
The TSA suggests that, before going through airport screening, patients with diabetes separate their diabetes supplies from their luggage and declare all items.6 Including prescription labels for medications and medical devices helps speed up the security process. Advise patients to carry glucose tablets and other solid foods for treating hypoglycemia when passing through airport security checkpoints.7
Since 2016, the TSA has allowed all diabetes-related supplies, medications, and equipment, including liquids and devices, through security after they have been screened by the x-ray scanner or by hand.7 People with diabetes are allowed to carry insulin and other liquid medications in amounts greater than 3.4 ounces (100 mLs) through airport security checkpoints.
Insulin can pass safely through x-ray scanners, but if patients are concerned, they may request that their insulin be inspected by hand.7 Patients must inform airport security of this decision before the screening process begins. A hand inspection may include swabbing for explosives.
Patients with an insulin pump and a continuous glucose monitoring device may feel uncomfortable during x-ray screening and special security screenings. Remind patients that it is TSA policy that patients do not need to disconnect their devices and can request screening by pat-down rather than x-ray scanner.6 It is the responsibility of the patient to research whether the pump can pass through x-ray scanners.
All patients have the right to request a pat-down and can opt out of passing through the x-ray scanner.6 However, patients need to inform officers about a pump before screening and must understand that the pump may be subject to further inspection. Usually, this additional inspection includes swabbing the patient’s hands to check for explosive material and a simple pat-down of the insulin pump.7
IN-FLIGHT TIPS
Time zones and insulin dosing
Diabetes management is often based on a 24-hour medication schedule. Travel can disrupt this schedule, making it challenging for patients to determine the appropriate medication adjustments. With some assistance, the patient can determine the best course of action based on the direction of travel and the number of time zones crossed.
According to Chandran and Edelman,7 medication adjustments are needed only when the patient is traveling east or west, not north or south. As time zones change, day length changes and, consequently, so does the 24-hour regimen many patients follow. As a general rule, traveling east results in a shortened day, requiring a potential reduction in insulin, while traveling west results in a longer day, possibly requiring an increase in insulin dose.7 However, this is a guideline and may not be applicable to all patients.7
Advise patients to follow local time to administer medications beginning the morning after arrival.7 It is not uncommon, due to changes in meal schedules and dosing, for patients to experience hyperglycemia during travel. They should be prepared to correct this if necessary.
Patients using insulin injections should plan to adjust to the new time zone as soon as possible. If the time change is only 1 or 2 hours, they should take their medications before departure according to their normal home time.7 Upon arrival, they should resume their insulin regimen based on the local time.
Westward travel. If the patient is traveling west with a time change of 3 or more hours, additional changes may be necessary. Advise patients to take their insulin according to their normal home time before departure. The change in dosing and schedule will depend largely on current glucose control, time of travel, and availability of food and glucose during travel. Encourage patients to discuss these matters with you in advance of any long travel.
Eastward travel. When the patient is traveling east with a time change greater than 3 hours, the day will be consequently shortened. On the day of travel, patients should take their morning dose according to home time. If they are concerned about hypoglycemia, suggest that they decrease the dose by 10%.6 On arrival, they should adhere to the new time zone and base insulin dosing on local time.
Advice for insulin pump users. Patients with an insulin pump need make only minimal changes to their dosing schedule. They should continue their routine of basal and bolus doses and change the time on their insulin pump to local time when they arrive. Insulin pump users should bring insulin and syringes as backup; in the event of pump malfunction, the patient should continue to use the same amount of bolus insulin to correct glucose readings and to cover meals.7 As for the basal dose, patients can administer a once-daily injection of long-acting insulin, which can be calculated from their pump or accessed from the list they created as part of their pre-travel preparation.7
Advice for patients on oral diabetes medications
If a patient is taking an oral medication, it is less crucial to adhere to a time schedule. In fact, in some cases it may be preferable to skip a dose and risk slight hyperglycemia for a few hours rather than take medication too close in time and risk hypoglycemia.7
Remind patients to anticipate a change in their oral medication regimen if they travel farther than 5 time zones.7 Encourage patients to research time changes and discuss the necessary changes in medication dosage on the day of travel as well as the specific aspects of their trip. A time-zone converter can be found at www.timeanddate.com.8
WHAT TO EXPECT WHILE ON LAND
Insulin 101
Storing insulin at the appropriate temperature may be a concern. Insulin should be kept between 40°F and 86°F (4°C–30°C).4 Remind patients to carry their insulin with them at all times and to not store it in a car glove compartment or backpack where it can be exposed to excessive sun. The Frio cold pack (ReadyCare, Walnut Creek, CA) is a helpful alternative to refrigeration and can be used to cool insulin when hiking or participating in activities where insulin can overheat. These cooling gel packs are activated when exposed to cold water for 5 to 7 minutes5 and are reusable.
Alert patients that insulin names and concentrations may vary among countries. Most insulins are U-100 concentration, which means that for every 1 mL of liquid there are 100 units of insulin. This is the standard insulin concentration used in the United States. There are U-200, U-300, and U-500 insulins as well. In Europe, the standard concentration is U-40 insulin. Syringe sizes are designed to accommodate either U-100 or U-40 insulin. Review these differences with patients and explain the consequences of mixing insulin concentration with syringes of different sizes. Figure 2 shows how to calculate equivalent doses.
Resort tips: Food, drinks, and excursions
A large component of travel is indulging in local cuisine. Patients with diabetes need to be aware of how different foods can affect their diabetes control. Encourage them to research the foods common to the local cuisine. Websites such as Calorie King, MyFitnessPal, Lose it!, and Nutrition Data can help identify the caloric and nutritional makeup of foods.9
Advise patients to actively monitor how their blood glucose is affected by new foods by checking blood glucose levels before and after each meal.9 Opting for vegetables and protein sources minimizes glucose fluctuations. Remind patients that drinks at resorts may contain more sugar than advertised. Patients should continue to manage their blood glucose by checking levels and by making appropriate insulin adjustments based on the readings. We often advise patients to pack a jar of peanut butter when traveling to ensure a ready source of protein.
Patients who plan to participate in physically challenging activities while travelling should inform all relevant members of the activity staff of their condition. In case of an emergency, hotel staff and guides will be better equipped to help with situations such as hypoglycemia. As noted above, patients should always carry snacks and supplies to treat hypoglycemia in case no alternative food options are available during an excursion. Also, warn patients to avoid walking barefoot. Water shoes are a good alternative to protect feet from cuts and sores.
Patients should inquire about the safety of high-elevation activities. With many glucose meters, every 1,000 feet of elevation results in a 1% to 2% underestimation of blood glucose,10 which could result in an inaccurate reading. If high-altitude activities are planned, advise patients to bring multiple meters to cross-check glucose readings in cases where inaccuracies (due to elevation) are possible.
Travel, once reserved for wealthy vacationers and high-level executives, has become a regular experience for many people. The US Travel and Tourism Overview reported that US domestic travel climbed to more than 2.25 billion person-trips in 2017.1 The US Centers for Disease Control and Prevention (CDC) and the US Travel Association suggest that, based on this frequency and the known rate of diabetes, 17 million people with diabetes travel annually for leisure and 5.6 million for business, and these numbers are expected to increase.2
It stands to reason that as the number of people who travel continues to increase, so too will the number of patients with diabetes seeking medical travel advice. Despite resources available to travelers with diabetes, researchers at the 2016 meeting of the American Diabetes Association noted that only 30% of patients with diabetes who responded to a survey reported being satisfied with the resources available to help them manage their diabetes while traveling.2 This article discusses how clinicians can help patients manage their diabetes while traveling, address common travel questions, and prepare patients for emergencies that may arise while traveling.
PRE-TRIP PREPARATION
Provider visit before travel: Checking the bases
Advise patients to schedule an appointment 4 to 6 weeks before their trip.3 At this appointment, give the patient a healthcare provider travel letter (Figure 1) and prescriptions that the patient can hand-carry en route.3 The provider letter should state that the patient has diabetes and should list all supplies the patient needs. The letter should also include specific medications used by the patient and the devices that deliver these medications, eg, Humalog insulin and U-100 syringes4 to administer insulin, as well as any food and medication allergies.
Prescriptions should be written for patients to use in the event of an emergency during travel. Prescriptions for diabetes medications should be written with generic names to minimize confusion for those traveling internationally. Additionally, all prescriptions should provide enough medication to last throughout the trip.4
Advise patients that rules for filling prescriptions may vary between states and countries.3 Also, the strength of insulin may vary between the United States and other countries. Patients should understand that if they fill their insulin prescription in a foreign country, they may need to purchase new syringes to match the insulin dose. For example, if patients use U-100 syringes and purchase U-40 insulin, they will need to buy U-40 syringes or risk taking too little of a dose.
Remind patients that prescriptions are not necessary for all diabetes supplies but are essential for coverage by insurance companies. Blood glucose testing supplies, ketone strips, and glucose tablets may be purchased in a pharmacy without a prescription. Human insulin may also be purchased over the counter. However, oral medications, glucagon, and analog insulins require a prescription. We suggest that patients who travel have their prescriptions on file at a chain pharmacy rather than an independent one. If they are in the United States, they can go to any branch of the chain pharmacy and easily fill a prescription.
Work with the patient to compile a separate document that details the medication dosing, correction-scale instructions, carbohydrate-to-insulin ratios, and pump settings (basal rates, insulin sensitivity, active insulin time).4 Patients who use an insulin pump should record all pump settings in the event that they need to convert to insulin injections during travel.4 We suggest that all patients with an insulin pump have an alternate insulin method (eg, pens, vials) and that they carry this with them along with basal insulin in case the pump fails. This level of preparation empowers the patient to assume responsibility for his or her own care if a healthcare provider is not available during travel.
Like all travelers, patients with diabetes should confirm that their immunizations are up to date. Encourage patients to the CDC’s page (wwwnc.cdc.gov/travel) to check the list of vaccines necessary for their region of travel.4,5 Many special immunizations can be acquired only from a public health department and not from a clinician’s office.
Additionally, depending on the region of travel, prescribing antibiotics or antidiarrheal medications may be necessary to ensure patient safety and comfort. We also recommend that patients with type 1 diabetes obtain a supply of antibiotics and antidiarrheals because they can become sick quickly.
Packing with diabetes: Double is better
The American Diabetes Association recommends that patients pack at least twice the medication and blood-testing supplies they anticipate needing.3 Reinforce to patients the need to pack all medications and supplies in their carry-on bag and to keep this bag in their possession at all times to avoid damage, loss, and extreme changes in temperature and air pressure, which can adversely affect the activity and stability of insulin.
Ask patients about the activities they plan to participate in and how many days they will be traveling, and then recommend shoes that will encourage appropriate foot care.4 Patients with diabetes should choose comfort over style when selecting footwear. All new shoes should be purchased and “broken in” 2 to 3 weeks before the trip. Alternating shoes decreases the risk of blisters and calluses.4
Emergency abroad: Planning to be prepared
It is crucial to counsel patients on how to respond in an emergency.
Encourage patients with diabetes, especially those who use insulin, to obtain a medical identification bracelet, necklace, or in some cases, a tattoo, that states they use insulin and discloses any allergies.3 This ensures that emergency medical personnel will be aware of the patient’s condition when providing care. Also suggest that your patients have emergency contact information available on their person and their cell phone to expedite assistance in an emergency (Table 2).
Urge patients to determine prior to their departure if their health coverage will change once they leave the state or the country. Some insurance companies require patients to go to a specific healthcare system while others regulate the amount of time a patient can be in the hospital before being transferred home. It is important for patients to be aware of these terms in the event of hospitalization.4 Travel insurance should be considered for international travel.
AIRPORT SECURITY: WHAT TO EXPECT WITH DIABETES
The American Diabetes Association works with the US Transportation Security Administration (TSA) to ensure that passengers with diabetes have access to supplies. Travelers with diabetes are allowed to apply for an optional disability notification card, which discreetly informs officers that the passenger has a condition or device that may affect screening procedures.6
The TSA suggests that, before going through airport screening, patients with diabetes separate their diabetes supplies from their luggage and declare all items.6 Including prescription labels for medications and medical devices helps speed up the security process. Advise patients to carry glucose tablets and other solid foods for treating hypoglycemia when passing through airport security checkpoints.7
Since 2016, the TSA has allowed all diabetes-related supplies, medications, and equipment, including liquids and devices, through security after they have been screened by the x-ray scanner or by hand.7 People with diabetes are allowed to carry insulin and other liquid medications in amounts greater than 3.4 ounces (100 mLs) through airport security checkpoints.
Insulin can pass safely through x-ray scanners, but if patients are concerned, they may request that their insulin be inspected by hand.7 Patients must inform airport security of this decision before the screening process begins. A hand inspection may include swabbing for explosives.
Patients with an insulin pump and a continuous glucose monitoring device may feel uncomfortable during x-ray screening and special security screenings. Remind patients that it is TSA policy that patients do not need to disconnect their devices and can request screening by pat-down rather than x-ray scanner.6 It is the responsibility of the patient to research whether the pump can pass through x-ray scanners.
All patients have the right to request a pat-down and can opt out of passing through the x-ray scanner.6 However, patients need to inform officers about a pump before screening and must understand that the pump may be subject to further inspection. Usually, this additional inspection includes swabbing the patient’s hands to check for explosive material and a simple pat-down of the insulin pump.7
IN-FLIGHT TIPS
Time zones and insulin dosing
Diabetes management is often based on a 24-hour medication schedule. Travel can disrupt this schedule, making it challenging for patients to determine the appropriate medication adjustments. With some assistance, the patient can determine the best course of action based on the direction of travel and the number of time zones crossed.
According to Chandran and Edelman,7 medication adjustments are needed only when the patient is traveling east or west, not north or south. As time zones change, day length changes and, consequently, so does the 24-hour regimen many patients follow. As a general rule, traveling east results in a shortened day, requiring a potential reduction in insulin, while traveling west results in a longer day, possibly requiring an increase in insulin dose.7 However, this is a guideline and may not be applicable to all patients.7
Advise patients to follow local time to administer medications beginning the morning after arrival.7 It is not uncommon, due to changes in meal schedules and dosing, for patients to experience hyperglycemia during travel. They should be prepared to correct this if necessary.
Patients using insulin injections should plan to adjust to the new time zone as soon as possible. If the time change is only 1 or 2 hours, they should take their medications before departure according to their normal home time.7 Upon arrival, they should resume their insulin regimen based on the local time.
Westward travel. If the patient is traveling west with a time change of 3 or more hours, additional changes may be necessary. Advise patients to take their insulin according to their normal home time before departure. The change in dosing and schedule will depend largely on current glucose control, time of travel, and availability of food and glucose during travel. Encourage patients to discuss these matters with you in advance of any long travel.
Eastward travel. When the patient is traveling east with a time change greater than 3 hours, the day will be consequently shortened. On the day of travel, patients should take their morning dose according to home time. If they are concerned about hypoglycemia, suggest that they decrease the dose by 10%.6 On arrival, they should adhere to the new time zone and base insulin dosing on local time.
Advice for insulin pump users. Patients with an insulin pump need make only minimal changes to their dosing schedule. They should continue their routine of basal and bolus doses and change the time on their insulin pump to local time when they arrive. Insulin pump users should bring insulin and syringes as backup; in the event of pump malfunction, the patient should continue to use the same amount of bolus insulin to correct glucose readings and to cover meals.7 As for the basal dose, patients can administer a once-daily injection of long-acting insulin, which can be calculated from their pump or accessed from the list they created as part of their pre-travel preparation.7
Advice for patients on oral diabetes medications
If a patient is taking an oral medication, it is less crucial to adhere to a time schedule. In fact, in some cases it may be preferable to skip a dose and risk slight hyperglycemia for a few hours rather than take medication too close in time and risk hypoglycemia.7
Remind patients to anticipate a change in their oral medication regimen if they travel farther than 5 time zones.7 Encourage patients to research time changes and discuss the necessary changes in medication dosage on the day of travel as well as the specific aspects of their trip. A time-zone converter can be found at www.timeanddate.com.8
WHAT TO EXPECT WHILE ON LAND
Insulin 101
Storing insulin at the appropriate temperature may be a concern. Insulin should be kept between 40°F and 86°F (4°C–30°C).4 Remind patients to carry their insulin with them at all times and to not store it in a car glove compartment or backpack where it can be exposed to excessive sun. The Frio cold pack (ReadyCare, Walnut Creek, CA) is a helpful alternative to refrigeration and can be used to cool insulin when hiking or participating in activities where insulin can overheat. These cooling gel packs are activated when exposed to cold water for 5 to 7 minutes5 and are reusable.
Alert patients that insulin names and concentrations may vary among countries. Most insulins are U-100 concentration, which means that for every 1 mL of liquid there are 100 units of insulin. This is the standard insulin concentration used in the United States. There are U-200, U-300, and U-500 insulins as well. In Europe, the standard concentration is U-40 insulin. Syringe sizes are designed to accommodate either U-100 or U-40 insulin. Review these differences with patients and explain the consequences of mixing insulin concentration with syringes of different sizes. Figure 2 shows how to calculate equivalent doses.
Resort tips: Food, drinks, and excursions
A large component of travel is indulging in local cuisine. Patients with diabetes need to be aware of how different foods can affect their diabetes control. Encourage them to research the foods common to the local cuisine. Websites such as Calorie King, MyFitnessPal, Lose it!, and Nutrition Data can help identify the caloric and nutritional makeup of foods.9
Advise patients to actively monitor how their blood glucose is affected by new foods by checking blood glucose levels before and after each meal.9 Opting for vegetables and protein sources minimizes glucose fluctuations. Remind patients that drinks at resorts may contain more sugar than advertised. Patients should continue to manage their blood glucose by checking levels and by making appropriate insulin adjustments based on the readings. We often advise patients to pack a jar of peanut butter when traveling to ensure a ready source of protein.
Patients who plan to participate in physically challenging activities while travelling should inform all relevant members of the activity staff of their condition. In case of an emergency, hotel staff and guides will be better equipped to help with situations such as hypoglycemia. As noted above, patients should always carry snacks and supplies to treat hypoglycemia in case no alternative food options are available during an excursion. Also, warn patients to avoid walking barefoot. Water shoes are a good alternative to protect feet from cuts and sores.
Patients should inquire about the safety of high-elevation activities. With many glucose meters, every 1,000 feet of elevation results in a 1% to 2% underestimation of blood glucose,10 which could result in an inaccurate reading. If high-altitude activities are planned, advise patients to bring multiple meters to cross-check glucose readings in cases where inaccuracies (due to elevation) are possible.
- US Travel Association. US travel and tourism overview. www.ustravel.org/system/files/media_root/document/Research_Fact-Sheet_US-Travel-and-Tourism-Overview.pdf. Accessed June 14, 2018.
- Brunk D. Long haul travel turbulent for many with type 1 diabetes. Clinical Endocrinology News 2016. www.mdedge.com/clinicalendocrinologynews/article/109866/diabetes/long-haul-travel-turbulent-many-type-1-diabetes. Accessed June 14, 2018.
- American Diabetes Association. When you travel. www.diabetes.org/living-with-diabetes/treatment-and-care/when-you-travel.html?utm_source=DSH_BLOG&utm_medium=BlogPost&utm_content=051514-travel&utm_campaign=CON. Accessed June 14, 2018.
- Kruger DF. The Diabetes Travel Guide. How to travel with diabetes-anywhere in the world. Arlington, VA: American Diabetes Association; 2000.
- Centers for Disease Control and Prevention. Travelers’ health. wwwnc.cdc.gov/travel/. Accessed June 14, 2018.
- American Diabetes Association. What special concerns may arise? www.diabetes.org/living-with-diabetes/know-your-rights/discrimination/public-accommodations/air-travel-and-diabetes/what-special-concerns-may.html. Accessed June 14, 2018.
- Chandran M, Edelman SV. Have insulin, will fly: diabetes management during air travel and time zone adjustment strategies. Clinical Diabetes 2003; 21(2):82–85. doi:10.2337/diaclin.21.2.82
- Time and Date AS. Time zone converter. timeanddate.com. Accessed March 19, 2018.
- Joslin Diabetes Center. Diabetes and travel—10 tips for a safe trip. www.joslin.org/info/diabetes_and_travel_10_tips_for_a_safe_trip.html. Accessed June 14, 2018.
- Jendle J, Adolfsson P. Impact of high altitudes on glucose control. J Diabetes Sci Technol 2011; 5(6):1621–1622. doi:10.1177/193229681100500642
- US Travel Association. US travel and tourism overview. www.ustravel.org/system/files/media_root/document/Research_Fact-Sheet_US-Travel-and-Tourism-Overview.pdf. Accessed June 14, 2018.
- Brunk D. Long haul travel turbulent for many with type 1 diabetes. Clinical Endocrinology News 2016. www.mdedge.com/clinicalendocrinologynews/article/109866/diabetes/long-haul-travel-turbulent-many-type-1-diabetes. Accessed June 14, 2018.
- American Diabetes Association. When you travel. www.diabetes.org/living-with-diabetes/treatment-and-care/when-you-travel.html?utm_source=DSH_BLOG&utm_medium=BlogPost&utm_content=051514-travel&utm_campaign=CON. Accessed June 14, 2018.
- Kruger DF. The Diabetes Travel Guide. How to travel with diabetes-anywhere in the world. Arlington, VA: American Diabetes Association; 2000.
- Centers for Disease Control and Prevention. Travelers’ health. wwwnc.cdc.gov/travel/. Accessed June 14, 2018.
- American Diabetes Association. What special concerns may arise? www.diabetes.org/living-with-diabetes/know-your-rights/discrimination/public-accommodations/air-travel-and-diabetes/what-special-concerns-may.html. Accessed June 14, 2018.
- Chandran M, Edelman SV. Have insulin, will fly: diabetes management during air travel and time zone adjustment strategies. Clinical Diabetes 2003; 21(2):82–85. doi:10.2337/diaclin.21.2.82
- Time and Date AS. Time zone converter. timeanddate.com. Accessed March 19, 2018.
- Joslin Diabetes Center. Diabetes and travel—10 tips for a safe trip. www.joslin.org/info/diabetes_and_travel_10_tips_for_a_safe_trip.html. Accessed June 14, 2018.
- Jendle J, Adolfsson P. Impact of high altitudes on glucose control. J Diabetes Sci Technol 2011; 5(6):1621–1622. doi:10.1177/193229681100500642
KEY POINTS
- Patients should pack all diabetes medications and supplies in a carry-on bag and keep it in their possession at all times.
- A travel letter will facilitate easy transfer through security and customs.
- Patients should always take more supplies than needed to accommodate changes in travel plans.
- If patients will cross multiple time zones during their travel, they will likely need to adjust their medication and food schedules.
