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Early intervention key to treating substance use disorders
SAN DIEGO – Intervening early can positively affect outcomes for patients struggling with substance use disorders, regardless of their current stage of development and place in the life cycle, speaker after speaker said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
The prenatal/perinatal period represents a high-risk window for the kindling and precipitation of substance use disorders (SUDs), because of the stress of pregnancy, delivery, recovery, and the newly assumed parenting role. “Offspring who are exposed in utero have an earlier age of initiation of substance use, as well as a greater risk of substance use disorders later on in life,” said Justine Wittenaur Welsh, MD, director of the Emory Adolescent Substance Use Treatment Services, Atlanta. “We as treatment providers need to start to think about how to screen for these individuals. What types of early intervention can we provide, and how do we integrate this into our treatment planning?”
According to data on current illicit drug use among pregnant women from the Substance Abuse and Mental Health Services Administration, the risk is highest among those aged 15-17 years (14.6%), followed by those aged 18-25 years (8.6%), and 26-44 years (3.2%). “We also know that rates of substance use are higher in the first trimester, compared with the second and the third,” said Dr. Welsh, who holds a faculty position in the department of psychiatry and behavioral sciences at Emory University. “But unfortunately, a significant number of pregnant women return to substance use after they deliver. This is really important for treatment providers, to intervene early before a return to substance use. We know that improving the postnatal environment does reduce the risk of substance use, even in individuals who have in utero exposures.”
SUDs confer a host of adverse effects to both the baby and the mother. “With tobacco, although there are a significant number of poisonous chemicals in cigarettes that the baby would be exposed to, we believe it’s the carbon monoxide and the nicotine exposure that confers the most known damage,” Dr. Welsh said. In utero exposure to cigarettes increases the likelihood to initiate smoking during adolescence by twofold (Neurotoxicol Teratol. 2005;27[2]:267-77), and a dose-response relationship has been observed between prenatal smoking and psychiatric hospitalization for substance abuse in offspring (Am J Psychiatry. 2002;159[1]:48-54). In utero exposure to cigarettes also increases the risk for offspring cigarette use. “The exposure to greater than a half-pack of cigarettes per day has a 5.5-fold increased risk for early cigarette experimentation, while exposure to one pack per day or more is associated with twice the risk of developing nicotine dependence,” she said.
As for in utero alcohol exposure, consuming greater than or equal to three drinks is associated with an alcohol disorder at age 21 (odds ratio, 2.95) if the exposure occurred in early pregnancy; Arch Gen Psychiatry. 2006;63[9]:1009-16). In utero alcohol exposure also has been more predictive of adolescent alcohol use than family history. “It’s also been associated with an increased number of abuse/dependency symptoms in offspring, for nicotine, alcohol, and illicit drugs,” Dr. Welsh said. “It has also been associated with an increased risk of cigarette use and substance use disorders in offspring.”
In utero cannabis exposure has been associated with a twofold increased risk of tobacco and marijuana use later in life (Addiction 2006;101[9]:1313-22), as well as with a twofold increased risk of smoking cigarettes daily and of using marijuana during adolescence. In utero cocaine exposure has been associated with a twofold increased risk of using tobacco, a 2.2-fold increased risk of using alcohol, and a 1.8-fold risk of using marijuana, as well as a 2.1-fold increased risk of having an SUD by age 17. “Prenatal exposure and postnatal parent/caregiver cocaine use is uniquely related to teen use of cocaine at age 14,” Dr. Welsh said. “In addition, exposure in the first trimester is associated with earlier marijuana and alcohol initiation.”
Real-world barriers to SUD treatment in adolescents include a lack of coordination between treatment resources, fear of losing custody of children, shame and stigma, concerns about criminal prosecution, domestic violence, and other obstacles such as transportation, finances, and child care. Dr. Welsh pointed out that pregnant women with SUDs usually receive prenatal care and addiction treatment from different providers. “We should be thinking about an integrated treatment model to improve maternal and prenatal care for patients using substances prior to or during pregnancy,” she said. “Some sites have developed combined maternity care units as a way to reduce some of these barriers to treatment. We also need to be thinking about the infants themselves. In order to counter the drug-exposed child’s early disadvantages, service providers must be prepared to intervene early, focusing on things like nutrition, psychomotor assessments, early educational needs assessments, as well as modification of existing treatment services for people with in utero exposures. This can be a difficult population to treat.”
One resource for addressing fetal alcohol spectrum disorders that she recommended is Treatment Improvement Protocol 58, published by Substance Abuse and Mental Health Services Administration. She described one young adult with significant substance use issues who was diagnosed with fetal alcohol syndrome as a child. “This young adult didn’t know about the FAS diagnosis,” Dr. Welsh said. “I expressed to the mother that, ‘this is an ethical dilemma. I’m treating someone and I know this directly impacts my treatment planning. They have a real-world diagnosis that I feel they have a right to know about.’ It made me think: If I think it’s so important that this young adult knows the diagnosis, why are we not screening for it in our general patient populations more often?
“As child psychiatrists we often ask, ‘Were there any in utero exposures?’ When treating adults, I’m asking about family history, but I’m not asking about in utero exposures. This may not be information that they’re privy to, but it’s worth starting a conversation about.”
, a 14-session, evidence-based curriculum that addresses parenting skills, children’s social skills, and family life skills training, are among the treatment options aimed at decreasing the risk of substance use progression in offspring.
‘Adolescents indeed care about their health’
During a separate presentation, Peter Jackson, MD, a psychiatrist at the University of Vermont Medical Center, Burlington, noted that an estimated 3.4 million adolescents in the United States meet criteria for an SUD, but fewer than 10% enter treatment each year. Of those who do enter treatment, 50% relapse within 6 months.
“It’s not the same story for illicit drugs, unfortunately, and that’s largely due to marijuana,” Dr. Jackson said. He noted that adolescent cannabis use is inversely proportional to how dangerous they perceive it to be. “This is evidence that adolescents indeed care about their health,” he said. “They use when they think it’s safe, and they use less when they think it’s unsafe.” Recent Monitoring the Future data also demonstrate that e-cigarette use is outpacing cigarette use among 8th, 10th, and 12th graders, while the past-year misuse of acetaminophen/hydrocodone (Vicodin) among 12th graders has dropped dramatically in the past 5 years. So has misuse of all prescription opioids among 12th graders despite high opioid overdose rates among adults.
Adolescents are more likely to be secretive about their substance use, compared with older adults. “Also, with many substances, especially alcohol, they are more likely to use in a binge pattern,” Dr. Jackson said. “They haven’t accumulated as many negative consequences from their use, so voluntarily seeking treatment is less common than in adults. They’re most often referred through the justice department or legal channels.”
Screening instruments to consider using include the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), which has been validated as an adolescent-specific screening instrument. A score of two or more has a strong correlation with meeting criteria for an SUD. The American Academy of Pediatrics recommends the Screening, Brief Intervention, and Referral to Treatment (SBIRT), though this intervention has not been as rigorously evaluated in adolescents, compared with adults.
Dr. Jackson frowned on the notion perpetuated by some parents and caregivers that novelty seeking behavior involving alcohol and other substances is okay if it’s controlled somehow, with statements such as, “I just make sure they’ve given up their car keys and make sure it stays in my own basement. That way nobody leaves here drunk.”
“I think we can do better than that,” Dr. Jackson said.
Well-validated behavioral treatment approaches for adolescent patients include the adolescent community reinforcement approach (A-CRA); cognitive-behavioral therapy (particularly in groups); motivational enhancement therapy (MET); contingency management, and 12-step facilitation.
“Colloquially, in pop culture, we’ve been pressed on this message at times that adolescents don’t care what their parents think; they only care what their peers think,” Dr. Jackson said. “That’s not true from literature we’ve seen, so we need to put the family back in its important place.”
In a meta-analysis of promising behavioral approaches for adolescent SUD, five out of six found to have promising to excellent empirical support were family-based therapies: multidimensional family therapy, functional family therapy, multisystemic family therapy, behavioral strategic family therapy, and family behavior therapy (J Child and Adolesc Psychology. 2008;37[1]:236-59). “That’s a huge take-home point when working with adolescents: Involve the family,” Dr. Jackson said. “As providers, do we have a tendency to side only with the parent or side only with the adolescent? If we do, we should be cautious and thoughtful, because we can very effectively work with both parties. If you have an adolescent who shows up [for counseling] but then walks right out the door, you still have a parent, maybe two parents or other concerned loved ones sitting there. You still have a target for intervention.”
Even if the adolescent never returns to your office, he continued, clinicians can do an intervention with the family to statistically decrease the SUD for the adolescent. “That’s really promising,” he said. In adults, the best evidence for treatment engagement of a loved one following these family-specific interventions is for the Community Reinforcement and Family Training (CRAFT) method (64%-74%), followed by the Johnson Intervention (23%-30%) and Al-Anon/Nar-Anon facilitation (13%-29%). These interventions are being studied more specifically in adolescents and young adults.
A key tip for parents of teens coping with substance abuse is the old adage actions speak louder than words. “You can tell your child not to smoke marijuana until you’re blue in the face, but then if you go out on the back porch and smoke marijuana, that’s a really bad message for behavior change,” Dr. Jackson said. “Words also speak louder than no words. Some parents have never told their adolescent children what their opinion is, and that they’re concerned. Maybe those parents have been convinced that adolescents don’t care what they think. In fact, they do care what they think.”
Once engaged, older adults do well
Among older adults, triggers for SUDs vary considerably from that of their younger counterparts. “We tend to think of this as a population that carries a lot of wisdom and has the coping skills to deal with life,” Olivera J. Bogunovic, MD, a psychiatrist who is medical director of ambulatory services in the division of alcohol and drug abuse at McClean Hospital, Belmont, Mass., said during a separate presentation. “In fact, this is a very vulnerable population at increased risk of mood disorders. For example, many men spend their careers working 60 or 80 hours a week, then they stop working. What is there for them? They sometimes turn to substance abuse. Similarly, older women who lose a loved one may turn to drinking. There’s a lot of room for prevention. The good news is that this group of patients is very responsive to treatment. Once engaged, they do very well.”
Nicotine is the chief addictive substance affecting older adults (17%), followed by alcohol (12% in a binge capacity, dependence 1%), illicit drugs (1.8%), and medications (1.6% for pain medications and 12% on benzodiazepines). Alcohol use disorders encompass a spectrum of problems for this patient population, including at-risk drinking, problem drinking, and dependence. Presentations, complications, and consequences are wide-ranging. “We sometimes miss the symptoms of alcohol use disorders when patients present in emergency rooms,” Dr. Bogunovic said. “Unfortunately, if it’s not treated initially it results in serious medical comorbidities and complications.”
The National Institute on Drug Abuse recommends that adults consume no more than two drinks per day, but the quantity is even lower for elderly. “For men it is no more than one drink per day, while for women it’s questionable if that one drink per day is even recommended,” Dr. Bogunovic said. The prevalence of at-risk drinking among older adults ranges from 3% to 25% and the rates for problem drinking range from 2.2% to 9.6%. Alcohol dependence rates, meanwhile, range from 2% to 3% among men and less than 1% among women.
Cross-sectional data indicate a low prevalence of illicit drug use in older adults, but longitudinal data from the National Survey on Drug Abuse and others suggest an increased use of cannabis and prescription opioids. “A lot of people do not think about opioid use disorders in the elderly,” she said. “The prevalence rate in methadone clinics is less than 2%. However, with the epidemic crisis we’re seeing opioid use disorders in the elderly. What’s important to know is that they also respond to medications for treatment, more so with suboxone than with naltrexone, as we know those patients sometimes have complications that need to be treated with pain medication.”
Elderly patients constitute 13% of the population yet they account for 30% of prescriptions, mainly benzodiazepines and prescription opioids. “Two-thirds of patients who are struggling with SUDs struggled with an SUD at some point in their youth,” said Dr. Bogunovic, who holds a faculty position in the department of psychiatry at Harvard Medical School, Boston. “They continue to use for longer periods of time, with some intermittent periods of sobriety. Of those 15% who do have an alcohol use problem, they are prescribed benzodiazepines. That can be a lethal combination, because there is a combined effect of both alcohol and benzodiazepines that can result in hip fractures, subdural hematomas, and other medical comorbidity.”
Risk factors for development of alcohol use disorder in elderly include physiologic changes in the way alcohol is metabolized; gender, family history, or prior personal history of alcohol use disorder; having a concomitant psychiatric disorder; and having a chronic medical illness, such as severe arthritis. Compared with their male peers, older women generally drink less often and less heavily, but they are more likely to start drinking heavily later in life. Older men face an increased risk of alcohol-related problems tied to cumulative use over the years.
“Social factors also play a role, so it’s important to perform a skilled diagnostic interview and a psychiatric evaluation but also to evaluate the motivational stage of change, because that’s the right moment to do the intervention, knowing what the patient’s values are,” she said. Recommended screenings include the Short Michigan Alcoholism Screening Instrument–Geriatric Version (SMAST-G), the SBIRT, the CAGE-AID, and the Opioid Risk Tool. Compliance with treatment tends to be greater in older adults, compared with their younger counterparts. “They don’t like a confrontational approach, so it’s important to communicate with empathy in a straightforward manner and pay attention to what is important to patients and motivate them,” she noted. “Involve family members or other social support whenever possible.”
Relapses are common, but clinicians should encourage patients to continue treatment, “because they can do very well,” Dr. Bogunovic emphasized. “And we can offer them a good life after that.”
Dr. Welsh disclosed that she has consulted for GW Pharmaceuticals and that she has received training fees from Chestnut Health Systems. Dr. Jackson and Dr. Bogunovic reported having no financial disclosures.
SAN DIEGO – Intervening early can positively affect outcomes for patients struggling with substance use disorders, regardless of their current stage of development and place in the life cycle, speaker after speaker said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
The prenatal/perinatal period represents a high-risk window for the kindling and precipitation of substance use disorders (SUDs), because of the stress of pregnancy, delivery, recovery, and the newly assumed parenting role. “Offspring who are exposed in utero have an earlier age of initiation of substance use, as well as a greater risk of substance use disorders later on in life,” said Justine Wittenaur Welsh, MD, director of the Emory Adolescent Substance Use Treatment Services, Atlanta. “We as treatment providers need to start to think about how to screen for these individuals. What types of early intervention can we provide, and how do we integrate this into our treatment planning?”
According to data on current illicit drug use among pregnant women from the Substance Abuse and Mental Health Services Administration, the risk is highest among those aged 15-17 years (14.6%), followed by those aged 18-25 years (8.6%), and 26-44 years (3.2%). “We also know that rates of substance use are higher in the first trimester, compared with the second and the third,” said Dr. Welsh, who holds a faculty position in the department of psychiatry and behavioral sciences at Emory University. “But unfortunately, a significant number of pregnant women return to substance use after they deliver. This is really important for treatment providers, to intervene early before a return to substance use. We know that improving the postnatal environment does reduce the risk of substance use, even in individuals who have in utero exposures.”
SUDs confer a host of adverse effects to both the baby and the mother. “With tobacco, although there are a significant number of poisonous chemicals in cigarettes that the baby would be exposed to, we believe it’s the carbon monoxide and the nicotine exposure that confers the most known damage,” Dr. Welsh said. In utero exposure to cigarettes increases the likelihood to initiate smoking during adolescence by twofold (Neurotoxicol Teratol. 2005;27[2]:267-77), and a dose-response relationship has been observed between prenatal smoking and psychiatric hospitalization for substance abuse in offspring (Am J Psychiatry. 2002;159[1]:48-54). In utero exposure to cigarettes also increases the risk for offspring cigarette use. “The exposure to greater than a half-pack of cigarettes per day has a 5.5-fold increased risk for early cigarette experimentation, while exposure to one pack per day or more is associated with twice the risk of developing nicotine dependence,” she said.
As for in utero alcohol exposure, consuming greater than or equal to three drinks is associated with an alcohol disorder at age 21 (odds ratio, 2.95) if the exposure occurred in early pregnancy; Arch Gen Psychiatry. 2006;63[9]:1009-16). In utero alcohol exposure also has been more predictive of adolescent alcohol use than family history. “It’s also been associated with an increased number of abuse/dependency symptoms in offspring, for nicotine, alcohol, and illicit drugs,” Dr. Welsh said. “It has also been associated with an increased risk of cigarette use and substance use disorders in offspring.”
In utero cannabis exposure has been associated with a twofold increased risk of tobacco and marijuana use later in life (Addiction 2006;101[9]:1313-22), as well as with a twofold increased risk of smoking cigarettes daily and of using marijuana during adolescence. In utero cocaine exposure has been associated with a twofold increased risk of using tobacco, a 2.2-fold increased risk of using alcohol, and a 1.8-fold risk of using marijuana, as well as a 2.1-fold increased risk of having an SUD by age 17. “Prenatal exposure and postnatal parent/caregiver cocaine use is uniquely related to teen use of cocaine at age 14,” Dr. Welsh said. “In addition, exposure in the first trimester is associated with earlier marijuana and alcohol initiation.”
Real-world barriers to SUD treatment in adolescents include a lack of coordination between treatment resources, fear of losing custody of children, shame and stigma, concerns about criminal prosecution, domestic violence, and other obstacles such as transportation, finances, and child care. Dr. Welsh pointed out that pregnant women with SUDs usually receive prenatal care and addiction treatment from different providers. “We should be thinking about an integrated treatment model to improve maternal and prenatal care for patients using substances prior to or during pregnancy,” she said. “Some sites have developed combined maternity care units as a way to reduce some of these barriers to treatment. We also need to be thinking about the infants themselves. In order to counter the drug-exposed child’s early disadvantages, service providers must be prepared to intervene early, focusing on things like nutrition, psychomotor assessments, early educational needs assessments, as well as modification of existing treatment services for people with in utero exposures. This can be a difficult population to treat.”
One resource for addressing fetal alcohol spectrum disorders that she recommended is Treatment Improvement Protocol 58, published by Substance Abuse and Mental Health Services Administration. She described one young adult with significant substance use issues who was diagnosed with fetal alcohol syndrome as a child. “This young adult didn’t know about the FAS diagnosis,” Dr. Welsh said. “I expressed to the mother that, ‘this is an ethical dilemma. I’m treating someone and I know this directly impacts my treatment planning. They have a real-world diagnosis that I feel they have a right to know about.’ It made me think: If I think it’s so important that this young adult knows the diagnosis, why are we not screening for it in our general patient populations more often?
“As child psychiatrists we often ask, ‘Were there any in utero exposures?’ When treating adults, I’m asking about family history, but I’m not asking about in utero exposures. This may not be information that they’re privy to, but it’s worth starting a conversation about.”
, a 14-session, evidence-based curriculum that addresses parenting skills, children’s social skills, and family life skills training, are among the treatment options aimed at decreasing the risk of substance use progression in offspring.
‘Adolescents indeed care about their health’
During a separate presentation, Peter Jackson, MD, a psychiatrist at the University of Vermont Medical Center, Burlington, noted that an estimated 3.4 million adolescents in the United States meet criteria for an SUD, but fewer than 10% enter treatment each year. Of those who do enter treatment, 50% relapse within 6 months.
“It’s not the same story for illicit drugs, unfortunately, and that’s largely due to marijuana,” Dr. Jackson said. He noted that adolescent cannabis use is inversely proportional to how dangerous they perceive it to be. “This is evidence that adolescents indeed care about their health,” he said. “They use when they think it’s safe, and they use less when they think it’s unsafe.” Recent Monitoring the Future data also demonstrate that e-cigarette use is outpacing cigarette use among 8th, 10th, and 12th graders, while the past-year misuse of acetaminophen/hydrocodone (Vicodin) among 12th graders has dropped dramatically in the past 5 years. So has misuse of all prescription opioids among 12th graders despite high opioid overdose rates among adults.
Adolescents are more likely to be secretive about their substance use, compared with older adults. “Also, with many substances, especially alcohol, they are more likely to use in a binge pattern,” Dr. Jackson said. “They haven’t accumulated as many negative consequences from their use, so voluntarily seeking treatment is less common than in adults. They’re most often referred through the justice department or legal channels.”
Screening instruments to consider using include the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), which has been validated as an adolescent-specific screening instrument. A score of two or more has a strong correlation with meeting criteria for an SUD. The American Academy of Pediatrics recommends the Screening, Brief Intervention, and Referral to Treatment (SBIRT), though this intervention has not been as rigorously evaluated in adolescents, compared with adults.
Dr. Jackson frowned on the notion perpetuated by some parents and caregivers that novelty seeking behavior involving alcohol and other substances is okay if it’s controlled somehow, with statements such as, “I just make sure they’ve given up their car keys and make sure it stays in my own basement. That way nobody leaves here drunk.”
“I think we can do better than that,” Dr. Jackson said.
Well-validated behavioral treatment approaches for adolescent patients include the adolescent community reinforcement approach (A-CRA); cognitive-behavioral therapy (particularly in groups); motivational enhancement therapy (MET); contingency management, and 12-step facilitation.
“Colloquially, in pop culture, we’ve been pressed on this message at times that adolescents don’t care what their parents think; they only care what their peers think,” Dr. Jackson said. “That’s not true from literature we’ve seen, so we need to put the family back in its important place.”
In a meta-analysis of promising behavioral approaches for adolescent SUD, five out of six found to have promising to excellent empirical support were family-based therapies: multidimensional family therapy, functional family therapy, multisystemic family therapy, behavioral strategic family therapy, and family behavior therapy (J Child and Adolesc Psychology. 2008;37[1]:236-59). “That’s a huge take-home point when working with adolescents: Involve the family,” Dr. Jackson said. “As providers, do we have a tendency to side only with the parent or side only with the adolescent? If we do, we should be cautious and thoughtful, because we can very effectively work with both parties. If you have an adolescent who shows up [for counseling] but then walks right out the door, you still have a parent, maybe two parents or other concerned loved ones sitting there. You still have a target for intervention.”
Even if the adolescent never returns to your office, he continued, clinicians can do an intervention with the family to statistically decrease the SUD for the adolescent. “That’s really promising,” he said. In adults, the best evidence for treatment engagement of a loved one following these family-specific interventions is for the Community Reinforcement and Family Training (CRAFT) method (64%-74%), followed by the Johnson Intervention (23%-30%) and Al-Anon/Nar-Anon facilitation (13%-29%). These interventions are being studied more specifically in adolescents and young adults.
A key tip for parents of teens coping with substance abuse is the old adage actions speak louder than words. “You can tell your child not to smoke marijuana until you’re blue in the face, but then if you go out on the back porch and smoke marijuana, that’s a really bad message for behavior change,” Dr. Jackson said. “Words also speak louder than no words. Some parents have never told their adolescent children what their opinion is, and that they’re concerned. Maybe those parents have been convinced that adolescents don’t care what they think. In fact, they do care what they think.”
Once engaged, older adults do well
Among older adults, triggers for SUDs vary considerably from that of their younger counterparts. “We tend to think of this as a population that carries a lot of wisdom and has the coping skills to deal with life,” Olivera J. Bogunovic, MD, a psychiatrist who is medical director of ambulatory services in the division of alcohol and drug abuse at McClean Hospital, Belmont, Mass., said during a separate presentation. “In fact, this is a very vulnerable population at increased risk of mood disorders. For example, many men spend their careers working 60 or 80 hours a week, then they stop working. What is there for them? They sometimes turn to substance abuse. Similarly, older women who lose a loved one may turn to drinking. There’s a lot of room for prevention. The good news is that this group of patients is very responsive to treatment. Once engaged, they do very well.”
Nicotine is the chief addictive substance affecting older adults (17%), followed by alcohol (12% in a binge capacity, dependence 1%), illicit drugs (1.8%), and medications (1.6% for pain medications and 12% on benzodiazepines). Alcohol use disorders encompass a spectrum of problems for this patient population, including at-risk drinking, problem drinking, and dependence. Presentations, complications, and consequences are wide-ranging. “We sometimes miss the symptoms of alcohol use disorders when patients present in emergency rooms,” Dr. Bogunovic said. “Unfortunately, if it’s not treated initially it results in serious medical comorbidities and complications.”
The National Institute on Drug Abuse recommends that adults consume no more than two drinks per day, but the quantity is even lower for elderly. “For men it is no more than one drink per day, while for women it’s questionable if that one drink per day is even recommended,” Dr. Bogunovic said. The prevalence of at-risk drinking among older adults ranges from 3% to 25% and the rates for problem drinking range from 2.2% to 9.6%. Alcohol dependence rates, meanwhile, range from 2% to 3% among men and less than 1% among women.
Cross-sectional data indicate a low prevalence of illicit drug use in older adults, but longitudinal data from the National Survey on Drug Abuse and others suggest an increased use of cannabis and prescription opioids. “A lot of people do not think about opioid use disorders in the elderly,” she said. “The prevalence rate in methadone clinics is less than 2%. However, with the epidemic crisis we’re seeing opioid use disorders in the elderly. What’s important to know is that they also respond to medications for treatment, more so with suboxone than with naltrexone, as we know those patients sometimes have complications that need to be treated with pain medication.”
Elderly patients constitute 13% of the population yet they account for 30% of prescriptions, mainly benzodiazepines and prescription opioids. “Two-thirds of patients who are struggling with SUDs struggled with an SUD at some point in their youth,” said Dr. Bogunovic, who holds a faculty position in the department of psychiatry at Harvard Medical School, Boston. “They continue to use for longer periods of time, with some intermittent periods of sobriety. Of those 15% who do have an alcohol use problem, they are prescribed benzodiazepines. That can be a lethal combination, because there is a combined effect of both alcohol and benzodiazepines that can result in hip fractures, subdural hematomas, and other medical comorbidity.”
Risk factors for development of alcohol use disorder in elderly include physiologic changes in the way alcohol is metabolized; gender, family history, or prior personal history of alcohol use disorder; having a concomitant psychiatric disorder; and having a chronic medical illness, such as severe arthritis. Compared with their male peers, older women generally drink less often and less heavily, but they are more likely to start drinking heavily later in life. Older men face an increased risk of alcohol-related problems tied to cumulative use over the years.
“Social factors also play a role, so it’s important to perform a skilled diagnostic interview and a psychiatric evaluation but also to evaluate the motivational stage of change, because that’s the right moment to do the intervention, knowing what the patient’s values are,” she said. Recommended screenings include the Short Michigan Alcoholism Screening Instrument–Geriatric Version (SMAST-G), the SBIRT, the CAGE-AID, and the Opioid Risk Tool. Compliance with treatment tends to be greater in older adults, compared with their younger counterparts. “They don’t like a confrontational approach, so it’s important to communicate with empathy in a straightforward manner and pay attention to what is important to patients and motivate them,” she noted. “Involve family members or other social support whenever possible.”
Relapses are common, but clinicians should encourage patients to continue treatment, “because they can do very well,” Dr. Bogunovic emphasized. “And we can offer them a good life after that.”
Dr. Welsh disclosed that she has consulted for GW Pharmaceuticals and that she has received training fees from Chestnut Health Systems. Dr. Jackson and Dr. Bogunovic reported having no financial disclosures.
SAN DIEGO – Intervening early can positively affect outcomes for patients struggling with substance use disorders, regardless of their current stage of development and place in the life cycle, speaker after speaker said at the annual meeting and scientific symposium of the American Academy of Addiction Psychiatry.
The prenatal/perinatal period represents a high-risk window for the kindling and precipitation of substance use disorders (SUDs), because of the stress of pregnancy, delivery, recovery, and the newly assumed parenting role. “Offspring who are exposed in utero have an earlier age of initiation of substance use, as well as a greater risk of substance use disorders later on in life,” said Justine Wittenaur Welsh, MD, director of the Emory Adolescent Substance Use Treatment Services, Atlanta. “We as treatment providers need to start to think about how to screen for these individuals. What types of early intervention can we provide, and how do we integrate this into our treatment planning?”
According to data on current illicit drug use among pregnant women from the Substance Abuse and Mental Health Services Administration, the risk is highest among those aged 15-17 years (14.6%), followed by those aged 18-25 years (8.6%), and 26-44 years (3.2%). “We also know that rates of substance use are higher in the first trimester, compared with the second and the third,” said Dr. Welsh, who holds a faculty position in the department of psychiatry and behavioral sciences at Emory University. “But unfortunately, a significant number of pregnant women return to substance use after they deliver. This is really important for treatment providers, to intervene early before a return to substance use. We know that improving the postnatal environment does reduce the risk of substance use, even in individuals who have in utero exposures.”
SUDs confer a host of adverse effects to both the baby and the mother. “With tobacco, although there are a significant number of poisonous chemicals in cigarettes that the baby would be exposed to, we believe it’s the carbon monoxide and the nicotine exposure that confers the most known damage,” Dr. Welsh said. In utero exposure to cigarettes increases the likelihood to initiate smoking during adolescence by twofold (Neurotoxicol Teratol. 2005;27[2]:267-77), and a dose-response relationship has been observed between prenatal smoking and psychiatric hospitalization for substance abuse in offspring (Am J Psychiatry. 2002;159[1]:48-54). In utero exposure to cigarettes also increases the risk for offspring cigarette use. “The exposure to greater than a half-pack of cigarettes per day has a 5.5-fold increased risk for early cigarette experimentation, while exposure to one pack per day or more is associated with twice the risk of developing nicotine dependence,” she said.
As for in utero alcohol exposure, consuming greater than or equal to three drinks is associated with an alcohol disorder at age 21 (odds ratio, 2.95) if the exposure occurred in early pregnancy; Arch Gen Psychiatry. 2006;63[9]:1009-16). In utero alcohol exposure also has been more predictive of adolescent alcohol use than family history. “It’s also been associated with an increased number of abuse/dependency symptoms in offspring, for nicotine, alcohol, and illicit drugs,” Dr. Welsh said. “It has also been associated with an increased risk of cigarette use and substance use disorders in offspring.”
In utero cannabis exposure has been associated with a twofold increased risk of tobacco and marijuana use later in life (Addiction 2006;101[9]:1313-22), as well as with a twofold increased risk of smoking cigarettes daily and of using marijuana during adolescence. In utero cocaine exposure has been associated with a twofold increased risk of using tobacco, a 2.2-fold increased risk of using alcohol, and a 1.8-fold risk of using marijuana, as well as a 2.1-fold increased risk of having an SUD by age 17. “Prenatal exposure and postnatal parent/caregiver cocaine use is uniquely related to teen use of cocaine at age 14,” Dr. Welsh said. “In addition, exposure in the first trimester is associated with earlier marijuana and alcohol initiation.”
Real-world barriers to SUD treatment in adolescents include a lack of coordination between treatment resources, fear of losing custody of children, shame and stigma, concerns about criminal prosecution, domestic violence, and other obstacles such as transportation, finances, and child care. Dr. Welsh pointed out that pregnant women with SUDs usually receive prenatal care and addiction treatment from different providers. “We should be thinking about an integrated treatment model to improve maternal and prenatal care for patients using substances prior to or during pregnancy,” she said. “Some sites have developed combined maternity care units as a way to reduce some of these barriers to treatment. We also need to be thinking about the infants themselves. In order to counter the drug-exposed child’s early disadvantages, service providers must be prepared to intervene early, focusing on things like nutrition, psychomotor assessments, early educational needs assessments, as well as modification of existing treatment services for people with in utero exposures. This can be a difficult population to treat.”
One resource for addressing fetal alcohol spectrum disorders that she recommended is Treatment Improvement Protocol 58, published by Substance Abuse and Mental Health Services Administration. She described one young adult with significant substance use issues who was diagnosed with fetal alcohol syndrome as a child. “This young adult didn’t know about the FAS diagnosis,” Dr. Welsh said. “I expressed to the mother that, ‘this is an ethical dilemma. I’m treating someone and I know this directly impacts my treatment planning. They have a real-world diagnosis that I feel they have a right to know about.’ It made me think: If I think it’s so important that this young adult knows the diagnosis, why are we not screening for it in our general patient populations more often?
“As child psychiatrists we often ask, ‘Were there any in utero exposures?’ When treating adults, I’m asking about family history, but I’m not asking about in utero exposures. This may not be information that they’re privy to, but it’s worth starting a conversation about.”
, a 14-session, evidence-based curriculum that addresses parenting skills, children’s social skills, and family life skills training, are among the treatment options aimed at decreasing the risk of substance use progression in offspring.
‘Adolescents indeed care about their health’
During a separate presentation, Peter Jackson, MD, a psychiatrist at the University of Vermont Medical Center, Burlington, noted that an estimated 3.4 million adolescents in the United States meet criteria for an SUD, but fewer than 10% enter treatment each year. Of those who do enter treatment, 50% relapse within 6 months.
“It’s not the same story for illicit drugs, unfortunately, and that’s largely due to marijuana,” Dr. Jackson said. He noted that adolescent cannabis use is inversely proportional to how dangerous they perceive it to be. “This is evidence that adolescents indeed care about their health,” he said. “They use when they think it’s safe, and they use less when they think it’s unsafe.” Recent Monitoring the Future data also demonstrate that e-cigarette use is outpacing cigarette use among 8th, 10th, and 12th graders, while the past-year misuse of acetaminophen/hydrocodone (Vicodin) among 12th graders has dropped dramatically in the past 5 years. So has misuse of all prescription opioids among 12th graders despite high opioid overdose rates among adults.
Adolescents are more likely to be secretive about their substance use, compared with older adults. “Also, with many substances, especially alcohol, they are more likely to use in a binge pattern,” Dr. Jackson said. “They haven’t accumulated as many negative consequences from their use, so voluntarily seeking treatment is less common than in adults. They’re most often referred through the justice department or legal channels.”
Screening instruments to consider using include the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), which has been validated as an adolescent-specific screening instrument. A score of two or more has a strong correlation with meeting criteria for an SUD. The American Academy of Pediatrics recommends the Screening, Brief Intervention, and Referral to Treatment (SBIRT), though this intervention has not been as rigorously evaluated in adolescents, compared with adults.
Dr. Jackson frowned on the notion perpetuated by some parents and caregivers that novelty seeking behavior involving alcohol and other substances is okay if it’s controlled somehow, with statements such as, “I just make sure they’ve given up their car keys and make sure it stays in my own basement. That way nobody leaves here drunk.”
“I think we can do better than that,” Dr. Jackson said.
Well-validated behavioral treatment approaches for adolescent patients include the adolescent community reinforcement approach (A-CRA); cognitive-behavioral therapy (particularly in groups); motivational enhancement therapy (MET); contingency management, and 12-step facilitation.
“Colloquially, in pop culture, we’ve been pressed on this message at times that adolescents don’t care what their parents think; they only care what their peers think,” Dr. Jackson said. “That’s not true from literature we’ve seen, so we need to put the family back in its important place.”
In a meta-analysis of promising behavioral approaches for adolescent SUD, five out of six found to have promising to excellent empirical support were family-based therapies: multidimensional family therapy, functional family therapy, multisystemic family therapy, behavioral strategic family therapy, and family behavior therapy (J Child and Adolesc Psychology. 2008;37[1]:236-59). “That’s a huge take-home point when working with adolescents: Involve the family,” Dr. Jackson said. “As providers, do we have a tendency to side only with the parent or side only with the adolescent? If we do, we should be cautious and thoughtful, because we can very effectively work with both parties. If you have an adolescent who shows up [for counseling] but then walks right out the door, you still have a parent, maybe two parents or other concerned loved ones sitting there. You still have a target for intervention.”
Even if the adolescent never returns to your office, he continued, clinicians can do an intervention with the family to statistically decrease the SUD for the adolescent. “That’s really promising,” he said. In adults, the best evidence for treatment engagement of a loved one following these family-specific interventions is for the Community Reinforcement and Family Training (CRAFT) method (64%-74%), followed by the Johnson Intervention (23%-30%) and Al-Anon/Nar-Anon facilitation (13%-29%). These interventions are being studied more specifically in adolescents and young adults.
A key tip for parents of teens coping with substance abuse is the old adage actions speak louder than words. “You can tell your child not to smoke marijuana until you’re blue in the face, but then if you go out on the back porch and smoke marijuana, that’s a really bad message for behavior change,” Dr. Jackson said. “Words also speak louder than no words. Some parents have never told their adolescent children what their opinion is, and that they’re concerned. Maybe those parents have been convinced that adolescents don’t care what they think. In fact, they do care what they think.”
Once engaged, older adults do well
Among older adults, triggers for SUDs vary considerably from that of their younger counterparts. “We tend to think of this as a population that carries a lot of wisdom and has the coping skills to deal with life,” Olivera J. Bogunovic, MD, a psychiatrist who is medical director of ambulatory services in the division of alcohol and drug abuse at McClean Hospital, Belmont, Mass., said during a separate presentation. “In fact, this is a very vulnerable population at increased risk of mood disorders. For example, many men spend their careers working 60 or 80 hours a week, then they stop working. What is there for them? They sometimes turn to substance abuse. Similarly, older women who lose a loved one may turn to drinking. There’s a lot of room for prevention. The good news is that this group of patients is very responsive to treatment. Once engaged, they do very well.”
Nicotine is the chief addictive substance affecting older adults (17%), followed by alcohol (12% in a binge capacity, dependence 1%), illicit drugs (1.8%), and medications (1.6% for pain medications and 12% on benzodiazepines). Alcohol use disorders encompass a spectrum of problems for this patient population, including at-risk drinking, problem drinking, and dependence. Presentations, complications, and consequences are wide-ranging. “We sometimes miss the symptoms of alcohol use disorders when patients present in emergency rooms,” Dr. Bogunovic said. “Unfortunately, if it’s not treated initially it results in serious medical comorbidities and complications.”
The National Institute on Drug Abuse recommends that adults consume no more than two drinks per day, but the quantity is even lower for elderly. “For men it is no more than one drink per day, while for women it’s questionable if that one drink per day is even recommended,” Dr. Bogunovic said. The prevalence of at-risk drinking among older adults ranges from 3% to 25% and the rates for problem drinking range from 2.2% to 9.6%. Alcohol dependence rates, meanwhile, range from 2% to 3% among men and less than 1% among women.
Cross-sectional data indicate a low prevalence of illicit drug use in older adults, but longitudinal data from the National Survey on Drug Abuse and others suggest an increased use of cannabis and prescription opioids. “A lot of people do not think about opioid use disorders in the elderly,” she said. “The prevalence rate in methadone clinics is less than 2%. However, with the epidemic crisis we’re seeing opioid use disorders in the elderly. What’s important to know is that they also respond to medications for treatment, more so with suboxone than with naltrexone, as we know those patients sometimes have complications that need to be treated with pain medication.”
Elderly patients constitute 13% of the population yet they account for 30% of prescriptions, mainly benzodiazepines and prescription opioids. “Two-thirds of patients who are struggling with SUDs struggled with an SUD at some point in their youth,” said Dr. Bogunovic, who holds a faculty position in the department of psychiatry at Harvard Medical School, Boston. “They continue to use for longer periods of time, with some intermittent periods of sobriety. Of those 15% who do have an alcohol use problem, they are prescribed benzodiazepines. That can be a lethal combination, because there is a combined effect of both alcohol and benzodiazepines that can result in hip fractures, subdural hematomas, and other medical comorbidity.”
Risk factors for development of alcohol use disorder in elderly include physiologic changes in the way alcohol is metabolized; gender, family history, or prior personal history of alcohol use disorder; having a concomitant psychiatric disorder; and having a chronic medical illness, such as severe arthritis. Compared with their male peers, older women generally drink less often and less heavily, but they are more likely to start drinking heavily later in life. Older men face an increased risk of alcohol-related problems tied to cumulative use over the years.
“Social factors also play a role, so it’s important to perform a skilled diagnostic interview and a psychiatric evaluation but also to evaluate the motivational stage of change, because that’s the right moment to do the intervention, knowing what the patient’s values are,” she said. Recommended screenings include the Short Michigan Alcoholism Screening Instrument–Geriatric Version (SMAST-G), the SBIRT, the CAGE-AID, and the Opioid Risk Tool. Compliance with treatment tends to be greater in older adults, compared with their younger counterparts. “They don’t like a confrontational approach, so it’s important to communicate with empathy in a straightforward manner and pay attention to what is important to patients and motivate them,” she noted. “Involve family members or other social support whenever possible.”
Relapses are common, but clinicians should encourage patients to continue treatment, “because they can do very well,” Dr. Bogunovic emphasized. “And we can offer them a good life after that.”
Dr. Welsh disclosed that she has consulted for GW Pharmaceuticals and that she has received training fees from Chestnut Health Systems. Dr. Jackson and Dr. Bogunovic reported having no financial disclosures.
EXPERT ANALYSIS FROM AAAP
High rate of arm morbidity in young breast cancer survivors
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
SAN ANTONIO – as compared with having a sentinel lymph node biopsy (SLNB), according to new findings.
In a large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger, the incidence of arm swelling 1 year after diagnosis among women who underwent breast-conserving surgery was 6% for the SLNB group versus 24% for those who had ALND. Among patients who had a mastectomy, the rates were similar; 6% versus 23% for SLNB or ALND, respectively.
“Young breast cancer survivors report high rates of arm morbidity in the first year of follow-up,” said lead author Anne Kuijer, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston. “Axillary node dissection, increased BMI [body mass index] and socioeconomic status were all independently associated with an increased risk of arm swelling,” she said at the San Antonio Breast Cancer Symposium.
She noted that patients who received mastectomy with radiation therapy were twice as likely to have decreased range of motion at 1 year, compared with patients treated with breast-conserving treatment.
In this study, the authors evaluated the incidence of arm morbidity associated with both ALND and SLNB in patients who were enrolled in the Young Women’s Breast Cancer Study. This multicenter prospective cohort study was designed to explore biological, medical, and psychosocial issues experienced by young breast cancer patients.
Within this large cohort, 55% had undergone an SLNB only, and 41% an ALND. The remaining patients did not undergo either procedure.
The primary endpoint of this study was to examine the incidence of patient-reported arm swelling or decreased range of motion at 1 year after their breast cancer diagnosis. Patients used the Cancer Rehabilitation Evaluation System (CARES-SF) to measure their symptoms.
Overall, at 1 year, 13% of the cohort reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Several factors were associated with a higher risk of arm morbidity. Patients with a BMI of greater than 25 were more likely to report arm swelling vs. those with lower BMI (odds ratio, 1.7; P = .03) as well as have less range of motion (OR, 1.5; P = .05). Women who reported feeling financially comfortable were 40% less likely to report swelling (P = .02) and 90% less likely to report decreased range of motion (P = .67).
In addition, those who underwent ALND were 3.4 times more likely to report swelling, compared with women who had SLNB, but it was not associated with a reduction in range of motion.
One limitation of the study is that the cohort included patients who had received treatment at large cancer centers in the Northeast, suggesting that they may have been of higher socioeconomic status and may have led more active lifestyles, compared with the general population. Another limitation is that arm morbidity was self-reported and not objectively measured.
“I think our findings highlight opportunities for preoperative counseling, early referral of patients to physical therapy, and identification of resources for support of those at increased risk,” said Dr. Kuijer.
SOURCE: Kuijer et al. SABCS Abstract GS5-03
REPORTING FROM SABCS 2017
Key clinical point: A significant rate of arm swelling and decreased range of motion was seen in young breast cancer patients 1 year after undergoing surgery.
Major finding: At 1 year, 13% of a large cohort of breast cancer patients aged 40 years or younger reported arm swelling, and 40% reported decreased range of motion in the ipsilateral arm.
Data source: Large prospective cohort study that included 1,302 breast cancer patients aged 40 or younger.
Disclosures:. This study was funded by the National Institutes of Health, the Susan G. Komen Foundation, The Pink Agenda, and the Breast Cancer Research Foundation. Dr. Kuijer and her colleagues declare no conflicts of interest.
Source: Kuijer et al. SABCS 2017 Abstract GS5-03.
Rituximab may be best choice for splenic MZL
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.
Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.
The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.
Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.
“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.
Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.
However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.
“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.
Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.
Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.
Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.
The researchers reported having no relevant financial disclosures.
SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.
FROM BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
Key clinical point:
Major finding: Both splenectomy and rituximab are associated with high rates of 10-year overalls survival, but splenectomy has higher rates of surgical complications and infection.
Study details: Review article of 63 publications, mostly retrospective studies of marginal zone lymphoma.
Disclosures: The researchers reported having no relevant financial disclosures.
Source: Kalpadakis C et al. Best Pract Res Clin Haematol. 2017 Mar-Jun. doi:10.1016/j.beha.2017.10.011.
Tatiana Falcone, MD
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Andrew G. Herzog, MD
Thapanee Somboon, MD
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Justin Gover
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Surgery residents cite time challenges to robotics training
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
FROM THE AMERICAN JOURNAL OF SURGERY
Key clinical point: .
Major finding: 80% of surgical residents said that the length of time needed to complete a robotics curriculum was a barrier to doing so.
Data source: Survey of 97 general surgery residents conducted in 2014-2015 and 2016-2017.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
Source: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Optimal Duration of Antiplatelet Therapy Following Acute Coronary Syndrome
ADA guidelines embrace heart health
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity. 
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
EXPERT ANALYSIS FROM DIABETES CARE