When I heard the American Academy of Pediatrics call for pediatricians to address poverty and social determinants of health, I – and maybe you, too – thought, “Great idea. But how am I, as a practicing pediatrician, supposed to help with such overwhelming and socially determined factors?”

It seems that the best way to reduce poverty, homelessness, and inadequate education is to advocate and vote to maintain or expand proven social programs. But there are also more proximal “relational” (relationship) factors we can address. The Adverse Childhood Experiences (ACE) study showed that the number of ACEs reported in their pasts by adults has a nearly linear relationship to long-term morbidities, including suicide, depression, obesity, smoking, substance abuse, heart disease, and early death. The ACE events during childhood – besides lack of food – came from the child’s relationships: abuse (emotional, physical, or sexual) and family dysfunction (mother abused; loss of a caregiver through divorce, separation, or death; household members with alcohol or substance abuse, mental illness, or time in prison).

The most important step you can take to prevent your patients from ACEs is detection. You have to ask parents, either verbally or with a screening tool about current factors that could be harmful to the child. You may think, “My patients don’t have these problems,” but abuse, intimate partner violence (IPV), depression, substance use, and loss occur in families of all kinds and means. Even the presence of food insecurity and imprisonment in some of my “put together” families has surprised me.

There are a number of tools available to screen for individual factors such as parental depression (Edinburgh Postnatal Screening, Patient Health Questionnaire-2 and -4), IPV, substance use (CRAFFT, which stands for Car, Relax, Alone, Forget, Friends, Trouble), and food insecurity. Tools covering multiple risk factors also are available on paper (Safe Environment for Every Kid [SEEK], Survey of Well-being of Young Children [SWYC]) or online (CHADIS). Rather than being overly intrusive, parents report accepting these questions as representing your caring about them as well as their child.

Coverage for screening and counseling for depression and IPV is mandated by the Affordable Care Act. As of July 2016, screening for maternal depression by pediatricians is paid for by Medicaid and many other insurers, often as part of the well-child visit, according to the Center for Medicaid and CHIP Services’ Informational Bulletin of May 11, 2016. For patient-centered medical homes, there is a mandate for referral and care coordination (AHRQ Publication No.11-M005-EF, December 2010). New value-based payment mechanisms are likely to pay you based on such screening and referral processes (e.g. New York), so we had best prepare (“Value-Based Payment Models for Medicaid Child Health Services,” Report to the Schuyler Center for Analysis and Advocacy and the United Hospital Fund, July 13, 2016).

But what to do when the screen or questions reveal a problem? Your first impulse is likely to be to refer. But unlike referrals for a physical health issue such as severe anemia for which the parent calls the hematologist immediately, in the case of these touchy, embarrassing, or emotionally charged problems, accepting help may not be so easy. It may be the financially critical partner who is the substance user or the mother herself who is too depressed to move towards help. For problems such as lack of food or the need to get a GED (general education development), the referral may be successful by supplying phone numbers. Referrals for IPV, one of the most common (greater than 29%) and damaging ACEs to the child, who is exposed to violence and often abused, have been found to mainly fail from simply making a referral.

Just as for a positive blood screen, for a referral to be effective more information is needed. In the case of a family stressor, you need to find out the nature and extent of the problem, the immediacy of the danger, and what has been done so far to reduce it. Research now shows that the most effective way to collect this information is using motivational interviewing (MI) techniques that nonjudgmentally determine not just the facts, but engage parents in weighing the pros and cons of changing the status quo, their readiness to change, the types of interventions that might be acceptable, and what would tell them that it was time to act. When using MI, you are actually doing more than making a referral, you are beginning to address the problem you uncovered.

RobertHoetink/Thinkstock

The MI process strengthens the trust in your relationship with the parent, starting with reflecting on the issue (“It sounds as though you don’t always feel safe at home”), empathizing (“That must be really scary. I am sorry you are going through that”), and assessing (“May I try to help you with this?”).

After collecting the pros and cons for making a change, either in the interview or via the screening tool SEEK Plus in CHADIS, your job is to help the parent weigh them (“On the one hand you love him and need his income, but on the other hand you are so afraid that you can’t sleep and your children are too nervous to concentrate in school.”) Then you need to elicit what would be enough to move them (“How will you know when it is time to act?”) and to assess readiness to change (“What kinds of help would you be open to?”), then offer that kind of help (“I would like to connect you to a professional who has a lot of experience helping people in your situation. Is it okay if we call her right now?”). Provide written contact information, of course, but actually assisting by calling the appropriate resource or even doing a “warm handoff” in person is more effective.

Obviously, to make an effective referral, we need resources assembled in advance for the most common issues. UnitedWay.org is a good place to include on your list.

Our job, however, is not over with an “accepted” referral. Most referrals are not kept, help is never received, and risk to the child is not averted. There are many potential barriers to families’ accessing help – time off work, money, transportation, or child care – but difficulty generating the courage to change is understandable and may resolve only gradually with your work and support. It is wise to tell the parent that “I (or someone on your staff) will check in on how this goes, okay?”

Making a follow-up appointment with you is important, even if you feel helpless to do more than refer. Why? A return visit is a chance to show that you care, to be sure they went, and to get information on the quality and appropriateness of the care provided so you can support it or refer elsewhere. Perhaps most importantly, it shows that you do not reject them for revealing what they may see as personal failure or immoral behavior so that you can continue caring for and monitoring their at-risk child.

What if they decline help, no resources are to be found, or the damage has already occurred? You still have valuable help to provide. Our goal is to ameliorate the impact of the stressors on the child now and in the future. Just as relational factors can stress the child, improving supportive relationships is key to reducing their effects. Parents with ACE risk factors are often self-absorbed in their pain, using smoking, substances, or alcohol to dampen it and moving from one troubled relationship to another in response to past trauma; thus they are emotionally unavailable to the child.

You can help them by focusing on the wonders of their child, encouraging daily individual time for play, and modeling Reach Out and Read as a supportive, calm activity they can do even when stressed. You can encourage the practice of mindfulness – an exercise of letting thoughts pass over them without judgment while breathing rhythmically – for stressed parents and school-aged children. It has been shown to be an effective intervention for recovering from past as well as current stress. Children also should receive any needed mental health care.

An emotionally available, supportive, nurturing parent is the most important protective factor for the child’s development of emotion regulation, resilience, and the ability to cope with adversity throughout their life. Referring parents to services such as home visiting, Healthy Steps, or parent-child therapy to build these skills has evidence for improving relational health. Helping the parents avoid ACEs for their children and assisting them in ameliorating them, if they occur, are important investments in long-term health that you can provide.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. Email her at [email protected].

When I heard the American Academy of Pediatrics call for pediatricians to address poverty and social determinants of health, I – and maybe you, too – thought, “Great idea. But how am I, as a practicing pediatrician, supposed to help with such overwhelming and socially determined factors?”

It seems that the best way to reduce poverty, homelessness, and inadequate education is to advocate and vote to maintain or expand proven social programs. But there are also more proximal “relational” (relationship) factors we can address. The Adverse Childhood Experiences (ACE) study showed that the number of ACEs reported in their pasts by adults has a nearly linear relationship to long-term morbidities, including suicide, depression, obesity, smoking, substance abuse, heart disease, and early death. The ACE events during childhood – besides lack of food – came from the child’s relationships: abuse (emotional, physical, or sexual) and family dysfunction (mother abused; loss of a caregiver through divorce, separation, or death; household members with alcohol or substance abuse, mental illness, or time in prison).

The most important step you can take to prevent your patients from ACEs is detection. You have to ask parents, either verbally or with a screening tool about current factors that could be harmful to the child. You may think, “My patients don’t have these problems,” but abuse, intimate partner violence (IPV), depression, substance use, and loss occur in families of all kinds and means. Even the presence of food insecurity and imprisonment in some of my “put together” families has surprised me.

There are a number of tools available to screen for individual factors such as parental depression (Edinburgh Postnatal Screening, Patient Health Questionnaire-2 and -4), IPV, substance use (CRAFFT, which stands for Car, Relax, Alone, Forget, Friends, Trouble), and food insecurity. Tools covering multiple risk factors also are available on paper (Safe Environment for Every Kid [SEEK], Survey of Well-being of Young Children [SWYC]) or online (CHADIS). Rather than being overly intrusive, parents report accepting these questions as representing your caring about them as well as their child.

Coverage for screening and counseling for depression and IPV is mandated by the Affordable Care Act. As of July 2016, screening for maternal depression by pediatricians is paid for by Medicaid and many other insurers, often as part of the well-child visit, according to the Center for Medicaid and CHIP Services’ Informational Bulletin of May 11, 2016. For patient-centered medical homes, there is a mandate for referral and care coordination (AHRQ Publication No.11-M005-EF, December 2010). New value-based payment mechanisms are likely to pay you based on such screening and referral processes (e.g. New York), so we had best prepare (“Value-Based Payment Models for Medicaid Child Health Services,” Report to the Schuyler Center for Analysis and Advocacy and the United Hospital Fund, July 13, 2016).

But what to do when the screen or questions reveal a problem? Your first impulse is likely to be to refer. But unlike referrals for a physical health issue such as severe anemia for which the parent calls the hematologist immediately, in the case of these touchy, embarrassing, or emotionally charged problems, accepting help may not be so easy. It may be the financially critical partner who is the substance user or the mother herself who is too depressed to move towards help. For problems such as lack of food or the need to get a GED (general education development), the referral may be successful by supplying phone numbers. Referrals for IPV, one of the most common (greater than 29%) and damaging ACEs to the child, who is exposed to violence and often abused, have been found to mainly fail from simply making a referral.

Just as for a positive blood screen, for a referral to be effective more information is needed. In the case of a family stressor, you need to find out the nature and extent of the problem, the immediacy of the danger, and what has been done so far to reduce it. Research now shows that the most effective way to collect this information is using motivational interviewing (MI) techniques that nonjudgmentally determine not just the facts, but engage parents in weighing the pros and cons of changing the status quo, their readiness to change, the types of interventions that might be acceptable, and what would tell them that it was time to act. When using MI, you are actually doing more than making a referral, you are beginning to address the problem you uncovered.

RobertHoetink/Thinkstock

The MI process strengthens the trust in your relationship with the parent, starting with reflecting on the issue (“It sounds as though you don’t always feel safe at home”), empathizing (“That must be really scary. I am sorry you are going through that”), and assessing (“May I try to help you with this?”).

After collecting the pros and cons for making a change, either in the interview or via the screening tool SEEK Plus in CHADIS, your job is to help the parent weigh them (“On the one hand you love him and need his income, but on the other hand you are so afraid that you can’t sleep and your children are too nervous to concentrate in school.”) Then you need to elicit what would be enough to move them (“How will you know when it is time to act?”) and to assess readiness to change (“What kinds of help would you be open to?”), then offer that kind of help (“I would like to connect you to a professional who has a lot of experience helping people in your situation. Is it okay if we call her right now?”). Provide written contact information, of course, but actually assisting by calling the appropriate resource or even doing a “warm handoff” in person is more effective.

Obviously, to make an effective referral, we need resources assembled in advance for the most common issues. UnitedWay.org is a good place to include on your list.

Our job, however, is not over with an “accepted” referral. Most referrals are not kept, help is never received, and risk to the child is not averted. There are many potential barriers to families’ accessing help – time off work, money, transportation, or child care – but difficulty generating the courage to change is understandable and may resolve only gradually with your work and support. It is wise to tell the parent that “I (or someone on your staff) will check in on how this goes, okay?”

Making a follow-up appointment with you is important, even if you feel helpless to do more than refer. Why? A return visit is a chance to show that you care, to be sure they went, and to get information on the quality and appropriateness of the care provided so you can support it or refer elsewhere. Perhaps most importantly, it shows that you do not reject them for revealing what they may see as personal failure or immoral behavior so that you can continue caring for and monitoring their at-risk child.

What if they decline help, no resources are to be found, or the damage has already occurred? You still have valuable help to provide. Our goal is to ameliorate the impact of the stressors on the child now and in the future. Just as relational factors can stress the child, improving supportive relationships is key to reducing their effects. Parents with ACE risk factors are often self-absorbed in their pain, using smoking, substances, or alcohol to dampen it and moving from one troubled relationship to another in response to past trauma; thus they are emotionally unavailable to the child.

You can help them by focusing on the wonders of their child, encouraging daily individual time for play, and modeling Reach Out and Read as a supportive, calm activity they can do even when stressed. You can encourage the practice of mindfulness – an exercise of letting thoughts pass over them without judgment while breathing rhythmically – for stressed parents and school-aged children. It has been shown to be an effective intervention for recovering from past as well as current stress. Children also should receive any needed mental health care.

An emotionally available, supportive, nurturing parent is the most important protective factor for the child’s development of emotion regulation, resilience, and the ability to cope with adversity throughout their life. Referring parents to services such as home visiting, Healthy Steps, or parent-child therapy to build these skills has evidence for improving relational health. Helping the parents avoid ACEs for their children and assisting them in ameliorating them, if they occur, are important investments in long-term health that you can provide.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. Email her at [email protected].

When I heard the American Academy of Pediatrics call for pediatricians to address poverty and social determinants of health, I – and maybe you, too – thought, “Great idea. But how am I, as a practicing pediatrician, supposed to help with such overwhelming and socially determined factors?”

It seems that the best way to reduce poverty, homelessness, and inadequate education is to advocate and vote to maintain or expand proven social programs. But there are also more proximal “relational” (relationship) factors we can address. The Adverse Childhood Experiences (ACE) study showed that the number of ACEs reported in their pasts by adults has a nearly linear relationship to long-term morbidities, including suicide, depression, obesity, smoking, substance abuse, heart disease, and early death. The ACE events during childhood – besides lack of food – came from the child’s relationships: abuse (emotional, physical, or sexual) and family dysfunction (mother abused; loss of a caregiver through divorce, separation, or death; household members with alcohol or substance abuse, mental illness, or time in prison).

The most important step you can take to prevent your patients from ACEs is detection. You have to ask parents, either verbally or with a screening tool about current factors that could be harmful to the child. You may think, “My patients don’t have these problems,” but abuse, intimate partner violence (IPV), depression, substance use, and loss occur in families of all kinds and means. Even the presence of food insecurity and imprisonment in some of my “put together” families has surprised me.

There are a number of tools available to screen for individual factors such as parental depression (Edinburgh Postnatal Screening, Patient Health Questionnaire-2 and -4), IPV, substance use (CRAFFT, which stands for Car, Relax, Alone, Forget, Friends, Trouble), and food insecurity. Tools covering multiple risk factors also are available on paper (Safe Environment for Every Kid [SEEK], Survey of Well-being of Young Children [SWYC]) or online (CHADIS). Rather than being overly intrusive, parents report accepting these questions as representing your caring about them as well as their child.

Coverage for screening and counseling for depression and IPV is mandated by the Affordable Care Act. As of July 2016, screening for maternal depression by pediatricians is paid for by Medicaid and many other insurers, often as part of the well-child visit, according to the Center for Medicaid and CHIP Services’ Informational Bulletin of May 11, 2016. For patient-centered medical homes, there is a mandate for referral and care coordination (AHRQ Publication No.11-M005-EF, December 2010). New value-based payment mechanisms are likely to pay you based on such screening and referral processes (e.g. New York), so we had best prepare (“Value-Based Payment Models for Medicaid Child Health Services,” Report to the Schuyler Center for Analysis and Advocacy and the United Hospital Fund, July 13, 2016).

But what to do when the screen or questions reveal a problem? Your first impulse is likely to be to refer. But unlike referrals for a physical health issue such as severe anemia for which the parent calls the hematologist immediately, in the case of these touchy, embarrassing, or emotionally charged problems, accepting help may not be so easy. It may be the financially critical partner who is the substance user or the mother herself who is too depressed to move towards help. For problems such as lack of food or the need to get a GED (general education development), the referral may be successful by supplying phone numbers. Referrals for IPV, one of the most common (greater than 29%) and damaging ACEs to the child, who is exposed to violence and often abused, have been found to mainly fail from simply making a referral.

Just as for a positive blood screen, for a referral to be effective more information is needed. In the case of a family stressor, you need to find out the nature and extent of the problem, the immediacy of the danger, and what has been done so far to reduce it. Research now shows that the most effective way to collect this information is using motivational interviewing (MI) techniques that nonjudgmentally determine not just the facts, but engage parents in weighing the pros and cons of changing the status quo, their readiness to change, the types of interventions that might be acceptable, and what would tell them that it was time to act. When using MI, you are actually doing more than making a referral, you are beginning to address the problem you uncovered.

RobertHoetink/Thinkstock

The MI process strengthens the trust in your relationship with the parent, starting with reflecting on the issue (“It sounds as though you don’t always feel safe at home”), empathizing (“That must be really scary. I am sorry you are going through that”), and assessing (“May I try to help you with this?”).

After collecting the pros and cons for making a change, either in the interview or via the screening tool SEEK Plus in CHADIS, your job is to help the parent weigh them (“On the one hand you love him and need his income, but on the other hand you are so afraid that you can’t sleep and your children are too nervous to concentrate in school.”) Then you need to elicit what would be enough to move them (“How will you know when it is time to act?”) and to assess readiness to change (“What kinds of help would you be open to?”), then offer that kind of help (“I would like to connect you to a professional who has a lot of experience helping people in your situation. Is it okay if we call her right now?”). Provide written contact information, of course, but actually assisting by calling the appropriate resource or even doing a “warm handoff” in person is more effective.

Obviously, to make an effective referral, we need resources assembled in advance for the most common issues. UnitedWay.org is a good place to include on your list.

Our job, however, is not over with an “accepted” referral. Most referrals are not kept, help is never received, and risk to the child is not averted. There are many potential barriers to families’ accessing help – time off work, money, transportation, or child care – but difficulty generating the courage to change is understandable and may resolve only gradually with your work and support. It is wise to tell the parent that “I (or someone on your staff) will check in on how this goes, okay?”

Making a follow-up appointment with you is important, even if you feel helpless to do more than refer. Why? A return visit is a chance to show that you care, to be sure they went, and to get information on the quality and appropriateness of the care provided so you can support it or refer elsewhere. Perhaps most importantly, it shows that you do not reject them for revealing what they may see as personal failure or immoral behavior so that you can continue caring for and monitoring their at-risk child.

What if they decline help, no resources are to be found, or the damage has already occurred? You still have valuable help to provide. Our goal is to ameliorate the impact of the stressors on the child now and in the future. Just as relational factors can stress the child, improving supportive relationships is key to reducing their effects. Parents with ACE risk factors are often self-absorbed in their pain, using smoking, substances, or alcohol to dampen it and moving from one troubled relationship to another in response to past trauma; thus they are emotionally unavailable to the child.

You can help them by focusing on the wonders of their child, encouraging daily individual time for play, and modeling Reach Out and Read as a supportive, calm activity they can do even when stressed. You can encourage the practice of mindfulness – an exercise of letting thoughts pass over them without judgment while breathing rhythmically – for stressed parents and school-aged children. It has been shown to be an effective intervention for recovering from past as well as current stress. Children also should receive any needed mental health care.

An emotionally available, supportive, nurturing parent is the most important protective factor for the child’s development of emotion regulation, resilience, and the ability to cope with adversity throughout their life. Referring parents to services such as home visiting, Healthy Steps, or parent-child therapy to build these skills has evidence for improving relational health. Helping the parents avoid ACEs for their children and assisting them in ameliorating them, if they occur, are important investments in long-term health that you can provide.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. Email her at [email protected].

TORONTO – A highly anticipated phase III trial of an anti-tau drug has posted negative topline results, conferring no cognitive or functional benefits when given in conjunction with standard-of-care Alzheimer’s disease medications.

The drug, LMTX (TauRx, Singapore), also did not slow the progression of brain atrophy on imaging in either of two doses tested, according to a company press release.

Although the study didn’t meet its clinical endpoints in the overall cohort of 891 patients with mild-moderate Alzheimer’s disease, TauRx promoted it as “promising,” based on a subgroup analysis of patients who took the drug as monotherapy. None of these patients were taking any standard-of-care Alzheimer’s medications; the press release did not say how many this group comprised. But it did imply that the group was small enough that the treatment effect was diluted in the pooled primary analysis.

In patients who took the drug as monotherapy, LMTX was associated with dose-dependent, statistically significant improvements in the Alzheimer’s Disease Assessment Scale measures of cognition (ADAS-cog) and Alzheimer’s Disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL). The drug was also associated with a slowing of brain ventricular expansion, compared with controls, suggesting that it could be preserving brain mass.

ADAS-cog scores for patients taking LMTX monotherapy 75 mg twice a day declined 6.3 points less than did controls, indicating preserved cognition. Those taking LMTX monotherapy 125 mg twice a day declined 5.8 points less than did controls. On the ADCS-ADL, patients taking 75 mg twice a day scored 6.5 points higher than controls, indicating better function, and those taking 125 mg twice a day scored 6.9 points higher.

Lateral ventricular volume expansion on MRI was significantly less than that seen in controls. For those taking 75 mg twice a day, ventricular expansion was reduced by 38%, and for those taking 125 mg twice a day, expansion was reduced by 33%.

This indicates a decrease in the rate of brain atrophy, the press release said, and the finding was “confirmed by corresponding increases in the whole-brain volumes in the same patient groups.”

The press release also said that the imaging findings offer physiologic confirmation of the cognitive and functional findings. “This is the first treatment in which a clinical effect has been supported by evidence in delay of progression in brain atrophy shown by MRI scans.”

The missing number of patients who took LMTX monotherapy is key, however, in determining whether the positive effects in that group are real or a chance finding, according to Richard J. Caselli, MD, associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic, Scottsdale, Ariz.

“Were the monotherapy results a fluke that washed out with bigger numbers or a meaningful effect? That needs to be clarified,” he said when asked to comment on the study. “Smaller ‘N’ trials can have skewed results due to random chances that mean nothing, and that is my fear. It’s unproven at this point but the burden of proof will rest on the investigators to replicate the positive outcome.”

The finding of a positive signal in monotherapy only is puzzling and also demands an explanation, said Michael Wolfe, PhD, a professor of neurology at Harvard University, Boston.

LMTX is a purified form of the dye methylene blue. Its method of action in preventing or dissolving tau tangles is not fully elucidated. A 2013 paper in a German chemistry journal, Angewandte Chemie, suggested that it works through oxidation to maintain the tau protein as a monomer, which prevents aggregation into filaments. There is no reason to think this pathway could intersect or interfere with any of the standard-of-care Alzheimer’s medications.

“There’s nothing obvious that comes to mind regarding interaction,” between the drug classes, Dr. Wolfe said in an interview. “We can’t say anything about this mechanistically. Any explanation here is just hand waving, I think.”

Dean Hartley, PhD, director of science initiatives at the Alzheimer’s Association, commented on the trial in a video interview at the Alzheimer’s Association International Conference 2016.

Neither Dr. Caselli nor Dr. Wolfe had relevant disclosures.

[email protected]

On Twitter @alz_gal

TORONTO – A highly anticipated phase III trial of an anti-tau drug has posted negative topline results, conferring no cognitive or functional benefits when given in conjunction with standard-of-care Alzheimer’s disease medications.

The drug, LMTX (TauRx, Singapore), also did not slow the progression of brain atrophy on imaging in either of two doses tested, according to a company press release.

Although the study didn’t meet its clinical endpoints in the overall cohort of 891 patients with mild-moderate Alzheimer’s disease, TauRx promoted it as “promising,” based on a subgroup analysis of patients who took the drug as monotherapy. None of these patients were taking any standard-of-care Alzheimer’s medications; the press release did not say how many this group comprised. But it did imply that the group was small enough that the treatment effect was diluted in the pooled primary analysis.

In patients who took the drug as monotherapy, LMTX was associated with dose-dependent, statistically significant improvements in the Alzheimer’s Disease Assessment Scale measures of cognition (ADAS-cog) and Alzheimer’s Disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL). The drug was also associated with a slowing of brain ventricular expansion, compared with controls, suggesting that it could be preserving brain mass.

ADAS-cog scores for patients taking LMTX monotherapy 75 mg twice a day declined 6.3 points less than did controls, indicating preserved cognition. Those taking LMTX monotherapy 125 mg twice a day declined 5.8 points less than did controls. On the ADCS-ADL, patients taking 75 mg twice a day scored 6.5 points higher than controls, indicating better function, and those taking 125 mg twice a day scored 6.9 points higher.

Lateral ventricular volume expansion on MRI was significantly less than that seen in controls. For those taking 75 mg twice a day, ventricular expansion was reduced by 38%, and for those taking 125 mg twice a day, expansion was reduced by 33%.

This indicates a decrease in the rate of brain atrophy, the press release said, and the finding was “confirmed by corresponding increases in the whole-brain volumes in the same patient groups.”

The press release also said that the imaging findings offer physiologic confirmation of the cognitive and functional findings. “This is the first treatment in which a clinical effect has been supported by evidence in delay of progression in brain atrophy shown by MRI scans.”

The missing number of patients who took LMTX monotherapy is key, however, in determining whether the positive effects in that group are real or a chance finding, according to Richard J. Caselli, MD, associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic, Scottsdale, Ariz.

“Were the monotherapy results a fluke that washed out with bigger numbers or a meaningful effect? That needs to be clarified,” he said when asked to comment on the study. “Smaller ‘N’ trials can have skewed results due to random chances that mean nothing, and that is my fear. It’s unproven at this point but the burden of proof will rest on the investigators to replicate the positive outcome.”

The finding of a positive signal in monotherapy only is puzzling and also demands an explanation, said Michael Wolfe, PhD, a professor of neurology at Harvard University, Boston.

LMTX is a purified form of the dye methylene blue. Its method of action in preventing or dissolving tau tangles is not fully elucidated. A 2013 paper in a German chemistry journal, Angewandte Chemie, suggested that it works through oxidation to maintain the tau protein as a monomer, which prevents aggregation into filaments. There is no reason to think this pathway could intersect or interfere with any of the standard-of-care Alzheimer’s medications.

“There’s nothing obvious that comes to mind regarding interaction,” between the drug classes, Dr. Wolfe said in an interview. “We can’t say anything about this mechanistically. Any explanation here is just hand waving, I think.”

Dean Hartley, PhD, director of science initiatives at the Alzheimer’s Association, commented on the trial in a video interview at the Alzheimer’s Association International Conference 2016.

Neither Dr. Caselli nor Dr. Wolfe had relevant disclosures.

[email protected]

On Twitter @alz_gal

TORONTO – A highly anticipated phase III trial of an anti-tau drug has posted negative topline results, conferring no cognitive or functional benefits when given in conjunction with standard-of-care Alzheimer’s disease medications.

The drug, LMTX (TauRx, Singapore), also did not slow the progression of brain atrophy on imaging in either of two doses tested, according to a company press release.

Although the study didn’t meet its clinical endpoints in the overall cohort of 891 patients with mild-moderate Alzheimer’s disease, TauRx promoted it as “promising,” based on a subgroup analysis of patients who took the drug as monotherapy. None of these patients were taking any standard-of-care Alzheimer’s medications; the press release did not say how many this group comprised. But it did imply that the group was small enough that the treatment effect was diluted in the pooled primary analysis.

In patients who took the drug as monotherapy, LMTX was associated with dose-dependent, statistically significant improvements in the Alzheimer’s Disease Assessment Scale measures of cognition (ADAS-cog) and Alzheimer’s Disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL). The drug was also associated with a slowing of brain ventricular expansion, compared with controls, suggesting that it could be preserving brain mass.

ADAS-cog scores for patients taking LMTX monotherapy 75 mg twice a day declined 6.3 points less than did controls, indicating preserved cognition. Those taking LMTX monotherapy 125 mg twice a day declined 5.8 points less than did controls. On the ADCS-ADL, patients taking 75 mg twice a day scored 6.5 points higher than controls, indicating better function, and those taking 125 mg twice a day scored 6.9 points higher.

Lateral ventricular volume expansion on MRI was significantly less than that seen in controls. For those taking 75 mg twice a day, ventricular expansion was reduced by 38%, and for those taking 125 mg twice a day, expansion was reduced by 33%.

This indicates a decrease in the rate of brain atrophy, the press release said, and the finding was “confirmed by corresponding increases in the whole-brain volumes in the same patient groups.”

The press release also said that the imaging findings offer physiologic confirmation of the cognitive and functional findings. “This is the first treatment in which a clinical effect has been supported by evidence in delay of progression in brain atrophy shown by MRI scans.”

The missing number of patients who took LMTX monotherapy is key, however, in determining whether the positive effects in that group are real or a chance finding, according to Richard J. Caselli, MD, associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic, Scottsdale, Ariz.

“Were the monotherapy results a fluke that washed out with bigger numbers or a meaningful effect? That needs to be clarified,” he said when asked to comment on the study. “Smaller ‘N’ trials can have skewed results due to random chances that mean nothing, and that is my fear. It’s unproven at this point but the burden of proof will rest on the investigators to replicate the positive outcome.”

The finding of a positive signal in monotherapy only is puzzling and also demands an explanation, said Michael Wolfe, PhD, a professor of neurology at Harvard University, Boston.

LMTX is a purified form of the dye methylene blue. Its method of action in preventing or dissolving tau tangles is not fully elucidated. A 2013 paper in a German chemistry journal, Angewandte Chemie, suggested that it works through oxidation to maintain the tau protein as a monomer, which prevents aggregation into filaments. There is no reason to think this pathway could intersect or interfere with any of the standard-of-care Alzheimer’s medications.

“There’s nothing obvious that comes to mind regarding interaction,” between the drug classes, Dr. Wolfe said in an interview. “We can’t say anything about this mechanistically. Any explanation here is just hand waving, I think.”

Dean Hartley, PhD, director of science initiatives at the Alzheimer’s Association, commented on the trial in a video interview at the Alzheimer’s Association International Conference 2016.

Neither Dr. Caselli nor Dr. Wolfe had relevant disclosures.

[email protected]

On Twitter @alz_gal

In the era where obesity is the No. 1 health crisis affecting people of all ages, physicians are often faced with questions regarding restricted diets or a patient may report that they are “vegetarian” in their history. Although new trendy diets appear all the time, “vegetarian inclined” diets are among the most common. A study conducted in 2008 identified that approximately 10% of Americans age 18 and older consumed a vegetarian diet.¹ It is important to know the basics so that you can offer some guidance and look for possible deficiencies that may result from an altered diet.

Studies show that children who follow a vegetarian diet have normal growth and development but tend to be leaner than their omnivore counterparts.² A healthy diet consumed in childhood lessens the risk for chronic diseases and promotes optimal growth and development. But altered or restricted diets in adolescents can be tricky because teens are actively growing and therefore usually need greater amounts of vital nutrients. So guidance is important to avoid common mistakes.

The simplest way to remember what is appropriate in a vegetarian diet is the restriction on intake of any food that once had a mother and a father. The vegetarian diet is further divided based on what it includes or excludes. Although the below list is not complete, it outlines the more common vegetarian diets:

• Vegan. This diet restricts intake of any animal product.

• Macrobiotics. This diet consists of whole grain, brown rice, fruits, and vegetables, and restricts intake of white meat or fish to twice a week.

• Lacto-vegetarian. This diet is one which allows milk products.

• Ovo vegetarian. – This diet allows eggs, but no meat, dairy, or fish.

• Pescitarian. This diet restricts meats, dairy, and eggs, but allows fish.

• Semi-vegetarian. This diet just restricts eating meat.

It is important to encourage anyone wishing to follow a vegetarian diet to fully research and understand what it entails. Health.gov under “dietary guidelines 2015-2020” is a wonderful reference to help understand how much of vital nutrients should be consumed to promote healthy eating habits and prevent deficiencies.

The key nutrients to discuss with patients are intake of protein, iron, calcium, vitamin B₁₂, and vitamin D. Inadequate or incorrect intake can lead to deficiency of the vital nutrients that likely will result in disease.

Protein is a necessary nutrient because it provides the essential amino acids necessary for growth and repair. When animal protein breaks down, it provides all of the essential amino acids, unlike plant protein which can be deficient in some of the amino acids. Because each source of plant protein varies in the amino acid it is deficient in, it is important to have a mixed source of protein to ensure adequate intake. The soy bean has comparable amounts of protein to animal protein. Other sources of protein are legumes, grain, cereal, eggs, nuts, Greek yogurt, cottage cheese, but these are less digestible so greater consumption is needed to meet the daily requirements. Deficiency in protein can result in impaired growth.

Iron that is obtained from animals or meat sources has heme component, which makes it easier to absorb. Iron obtained from plants does not contain heme component and therefore is more difficult to absorb. Ascorbic acid (vitamin C) helps nonheme iron to be absorbed, but must be taken with an iron source to be effective. Therefore, vitamin C–containing foods such as fruits and vegetables should be consumed at every meal to assist in iron absorption. Deficiency in iron can lead to anemia and reduced energy.

Calcium is an important nutrient for bone formation, and deficiency can lead to increased risk for fracture and osteoporosis later in life. Its excretion and absorption can be affected by other nutrients, such as iron and zinc, present during digestion. Milk and dairy products are the most common source for calcium intake, but there are other calcium sources such as kale, broccoli, and food fortified with calcium such as cereal and orange juice. These foods can be better sources of calcium than supplements because they allow for better absorption.

Vitamin D is needed for calcium and phosphorus absorption, which is important for proper bone formation. Vitamin D is found in dairy products, fortified food and beverages, and exposure to the sun. Those living in colder climates and of darker pigmentation are at greater risk of deficiency so supplementation is usually necessary. Deficiency of vitamin D can lead to rickets.

Vitamin B₁₂ is found in meat, fish, and dairy products, but not in plants. Intake of B₁₂ is likely to be deficient in vegans because they do not consume most of those sources. Vegans are at a significant risk of vitamin B₁₂ deficiency³ which can lead to macrocytosis, anemia, and decreased energy.

Educating families on healthy eating is essential at any visit. A good understanding of the possible deficiencies that can occur with restricted diets will allow for proper guidance and avoidable diseases.

References

1. Stahler C. “How Many Youth Are Vegetarian? The Vegetarian Resource Group Asks in a 2010 National Poll.”

2. Pediatrics. 1989 Sep;84(3):475-81.

3. J Am Diet Assoc. 2003 Jun;103(6):771-5.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

In the era where obesity is the No. 1 health crisis affecting people of all ages, physicians are often faced with questions regarding restricted diets or a patient may report that they are “vegetarian” in their history. Although new trendy diets appear all the time, “vegetarian inclined” diets are among the most common. A study conducted in 2008 identified that approximately 10% of Americans age 18 and older consumed a vegetarian diet.¹ It is important to know the basics so that you can offer some guidance and look for possible deficiencies that may result from an altered diet.

Studies show that children who follow a vegetarian diet have normal growth and development but tend to be leaner than their omnivore counterparts.² A healthy diet consumed in childhood lessens the risk for chronic diseases and promotes optimal growth and development. But altered or restricted diets in adolescents can be tricky because teens are actively growing and therefore usually need greater amounts of vital nutrients. So guidance is important to avoid common mistakes.

The simplest way to remember what is appropriate in a vegetarian diet is the restriction on intake of any food that once had a mother and a father. The vegetarian diet is further divided based on what it includes or excludes. Although the below list is not complete, it outlines the more common vegetarian diets:

• Vegan. This diet restricts intake of any animal product.

• Macrobiotics. This diet consists of whole grain, brown rice, fruits, and vegetables, and restricts intake of white meat or fish to twice a week.

• Lacto-vegetarian. This diet is one which allows milk products.

• Ovo vegetarian. – This diet allows eggs, but no meat, dairy, or fish.

• Pescitarian. This diet restricts meats, dairy, and eggs, but allows fish.

• Semi-vegetarian. This diet just restricts eating meat.

It is important to encourage anyone wishing to follow a vegetarian diet to fully research and understand what it entails. Health.gov under “dietary guidelines 2015-2020” is a wonderful reference to help understand how much of vital nutrients should be consumed to promote healthy eating habits and prevent deficiencies.

The key nutrients to discuss with patients are intake of protein, iron, calcium, vitamin B₁₂, and vitamin D. Inadequate or incorrect intake can lead to deficiency of the vital nutrients that likely will result in disease.

Protein is a necessary nutrient because it provides the essential amino acids necessary for growth and repair. When animal protein breaks down, it provides all of the essential amino acids, unlike plant protein which can be deficient in some of the amino acids. Because each source of plant protein varies in the amino acid it is deficient in, it is important to have a mixed source of protein to ensure adequate intake. The soy bean has comparable amounts of protein to animal protein. Other sources of protein are legumes, grain, cereal, eggs, nuts, Greek yogurt, cottage cheese, but these are less digestible so greater consumption is needed to meet the daily requirements. Deficiency in protein can result in impaired growth.

Iron that is obtained from animals or meat sources has heme component, which makes it easier to absorb. Iron obtained from plants does not contain heme component and therefore is more difficult to absorb. Ascorbic acid (vitamin C) helps nonheme iron to be absorbed, but must be taken with an iron source to be effective. Therefore, vitamin C–containing foods such as fruits and vegetables should be consumed at every meal to assist in iron absorption. Deficiency in iron can lead to anemia and reduced energy.

Calcium is an important nutrient for bone formation, and deficiency can lead to increased risk for fracture and osteoporosis later in life. Its excretion and absorption can be affected by other nutrients, such as iron and zinc, present during digestion. Milk and dairy products are the most common source for calcium intake, but there are other calcium sources such as kale, broccoli, and food fortified with calcium such as cereal and orange juice. These foods can be better sources of calcium than supplements because they allow for better absorption.

Vitamin D is needed for calcium and phosphorus absorption, which is important for proper bone formation. Vitamin D is found in dairy products, fortified food and beverages, and exposure to the sun. Those living in colder climates and of darker pigmentation are at greater risk of deficiency so supplementation is usually necessary. Deficiency of vitamin D can lead to rickets.

Vitamin B₁₂ is found in meat, fish, and dairy products, but not in plants. Intake of B₁₂ is likely to be deficient in vegans because they do not consume most of those sources. Vegans are at a significant risk of vitamin B₁₂ deficiency³ which can lead to macrocytosis, anemia, and decreased energy.

Educating families on healthy eating is essential at any visit. A good understanding of the possible deficiencies that can occur with restricted diets will allow for proper guidance and avoidable diseases.

References

1. Stahler C. “How Many Youth Are Vegetarian? The Vegetarian Resource Group Asks in a 2010 National Poll.”

2. Pediatrics. 1989 Sep;84(3):475-81.

3. J Am Diet Assoc. 2003 Jun;103(6):771-5.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

In the era where obesity is the No. 1 health crisis affecting people of all ages, physicians are often faced with questions regarding restricted diets or a patient may report that they are “vegetarian” in their history. Although new trendy diets appear all the time, “vegetarian inclined” diets are among the most common. A study conducted in 2008 identified that approximately 10% of Americans age 18 and older consumed a vegetarian diet.¹ It is important to know the basics so that you can offer some guidance and look for possible deficiencies that may result from an altered diet.

Studies show that children who follow a vegetarian diet have normal growth and development but tend to be leaner than their omnivore counterparts.² A healthy diet consumed in childhood lessens the risk for chronic diseases and promotes optimal growth and development. But altered or restricted diets in adolescents can be tricky because teens are actively growing and therefore usually need greater amounts of vital nutrients. So guidance is important to avoid common mistakes.

The simplest way to remember what is appropriate in a vegetarian diet is the restriction on intake of any food that once had a mother and a father. The vegetarian diet is further divided based on what it includes or excludes. Although the below list is not complete, it outlines the more common vegetarian diets:

• Vegan. This diet restricts intake of any animal product.

• Macrobiotics. This diet consists of whole grain, brown rice, fruits, and vegetables, and restricts intake of white meat or fish to twice a week.

• Lacto-vegetarian. This diet is one which allows milk products.

• Ovo vegetarian. – This diet allows eggs, but no meat, dairy, or fish.

• Pescitarian. This diet restricts meats, dairy, and eggs, but allows fish.

• Semi-vegetarian. This diet just restricts eating meat.

It is important to encourage anyone wishing to follow a vegetarian diet to fully research and understand what it entails. Health.gov under “dietary guidelines 2015-2020” is a wonderful reference to help understand how much of vital nutrients should be consumed to promote healthy eating habits and prevent deficiencies.

The key nutrients to discuss with patients are intake of protein, iron, calcium, vitamin B₁₂, and vitamin D. Inadequate or incorrect intake can lead to deficiency of the vital nutrients that likely will result in disease.

Protein is a necessary nutrient because it provides the essential amino acids necessary for growth and repair. When animal protein breaks down, it provides all of the essential amino acids, unlike plant protein which can be deficient in some of the amino acids. Because each source of plant protein varies in the amino acid it is deficient in, it is important to have a mixed source of protein to ensure adequate intake. The soy bean has comparable amounts of protein to animal protein. Other sources of protein are legumes, grain, cereal, eggs, nuts, Greek yogurt, cottage cheese, but these are less digestible so greater consumption is needed to meet the daily requirements. Deficiency in protein can result in impaired growth.

Iron that is obtained from animals or meat sources has heme component, which makes it easier to absorb. Iron obtained from plants does not contain heme component and therefore is more difficult to absorb. Ascorbic acid (vitamin C) helps nonheme iron to be absorbed, but must be taken with an iron source to be effective. Therefore, vitamin C–containing foods such as fruits and vegetables should be consumed at every meal to assist in iron absorption. Deficiency in iron can lead to anemia and reduced energy.

Calcium is an important nutrient for bone formation, and deficiency can lead to increased risk for fracture and osteoporosis later in life. Its excretion and absorption can be affected by other nutrients, such as iron and zinc, present during digestion. Milk and dairy products are the most common source for calcium intake, but there are other calcium sources such as kale, broccoli, and food fortified with calcium such as cereal and orange juice. These foods can be better sources of calcium than supplements because they allow for better absorption.

Vitamin D is needed for calcium and phosphorus absorption, which is important for proper bone formation. Vitamin D is found in dairy products, fortified food and beverages, and exposure to the sun. Those living in colder climates and of darker pigmentation are at greater risk of deficiency so supplementation is usually necessary. Deficiency of vitamin D can lead to rickets.

Vitamin B₁₂ is found in meat, fish, and dairy products, but not in plants. Intake of B₁₂ is likely to be deficient in vegans because they do not consume most of those sources. Vegans are at a significant risk of vitamin B₁₂ deficiency³ which can lead to macrocytosis, anemia, and decreased energy.

Educating families on healthy eating is essential at any visit. A good understanding of the possible deficiencies that can occur with restricted diets will allow for proper guidance and avoidable diseases.

References

1. Stahler C. “How Many Youth Are Vegetarian? The Vegetarian Resource Group Asks in a 2010 National Poll.”

2. Pediatrics. 1989 Sep;84(3):475-81.

3. J Am Diet Assoc. 2003 Jun;103(6):771-5.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.