SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).

grandeduc/Thinkstock

ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).

“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”

In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).

There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.

Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.

“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.

The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.

SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.

SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).

grandeduc/Thinkstock

ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).

“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”

In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).

There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.

Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.

“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.

The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.

SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.

SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).

grandeduc/Thinkstock

ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).

“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”

In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).

There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.

Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.

“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.

The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.

SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.

Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.

It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.

Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”²

The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.

After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.^3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.

At a larger level, we are unsure that the newer psychotropics are particularly better than older ones. The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.⁵ Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.⁶ As famously described in the CATIE trial⁷ of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis⁸ did not find significant differences among antipsychotics’ efficacy.

A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9

The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,¹⁰ and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.¹¹

We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.

However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?

A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.



Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
 

References

1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.

2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.

3. Am J Emerg Med. 2016 Feb;34(2):133-9.

4. Eur Psychiatry. 2018 Feb;48:6-12.

5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.

6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.

7. N Engl J Med. 2005 Sep 22;353(12):1209-23.

8. Am J Psychiatry. 2017. 174(10):927-42.

9. Lancet. 2018 Apr 7. 391(10128):P1357-66.

10. BMJ. 2009.339;b2880.

11. https://breggin.com/.

Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.

It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.

Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”²

The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.

After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.^3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.

At a larger level, we are unsure that the newer psychotropics are particularly better than older ones. The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.⁵ Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.⁶ As famously described in the CATIE trial⁷ of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis⁸ did not find significant differences among antipsychotics’ efficacy.

A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9

The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,¹⁰ and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.¹¹

We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.

However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?

A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.



Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
 

References

1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.

2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.

3. Am J Emerg Med. 2016 Feb;34(2):133-9.

4. Eur Psychiatry. 2018 Feb;48:6-12.

5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.

6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.

7. N Engl J Med. 2005 Sep 22;353(12):1209-23.

8. Am J Psychiatry. 2017. 174(10):927-42.

9. Lancet. 2018 Apr 7. 391(10128):P1357-66.

10. BMJ. 2009.339;b2880.

11. https://breggin.com/.

Since the biological revolution in psychiatry, with the introduction of chlorpromazine in the 1950s,1 psychiatrists have been introduced to the economic questions inherent in the tension between funding psychotropic medications for the treatment of mental illness versus funding psychosocial interventions. Of course, our natural inclination is to advocate for all available treatments for our patients, but the economic realities of medical care – especially government-subsidized or regulated medical care – force us to weigh the relative advantages of these treatments and to promote our patients’ interests with a wise allocation of limited resources.

It has become common practice for the American Psychiatric Association to advocate for additional funds for both research into mental illness as well as treatment. The promotion of mental health parity and the demonization of prior authorizations are examples of our natural priorities in the debates over funding for medical care. A bias has played out in the national conversation about medical care in general regarding the right to said care, but economists understand that medical care is a limited resource and, as such, treating it as a “right,” per se, does not make sense: One has to make hard decisions about its allocation or simply leave it to the free market to make said decisions.

Recently, the government has proposed to eliminate certain psychotropic medications from their protected status within Medicare Part D. Those medications include all drugs labeled as antidepressants, antipsychotics, and anticonvulsants. As expected, the APA’s medical director has written a formal statement opposing the proposal. His statement includes warnings about suicides and overwhelmed emergency departments. He compared the mental health situation in the United States to a crisis. He described the availability of expensive and new psychotropics to be “lifesaving.”²

The goals of the APA and its leaders are honorable. We are inspired by the dedication that some psychiatrists have to advocate for us all as well as for our patients. However, we are concerned that unfounded claims are being made. We are even more troubled when those claims promote the interests of a fallible pharmaceutical industry, an industry that has opened up our field to extensive critical scrutiny over the past few years. We wonder whether a brief examination of the scientific evidence warrants the statements made by the APA.

After reviewing clinical textbooks and search engines, we were not able to find reliable and convincing evidence that newer psychotropics reduce emergency department stays or that lengths of stay in the hospital correlate with the use of newer agents. We have actually not even heard of that claim made before in any serious forum. Reviews of predictors of length of stay in psychiatric hospitals have typically included demographic factors, diagnostic factors, logistical factors such as time of day, and social factors, such as insurance status and homelessness.^3,4 We found no review mentioning the use of patented drugs as a predictor of shorter stays.

At a larger level, we are unsure that the newer psychotropics are particularly better than older ones. The Food and Drug Administration approves psychiatric medications based on superiority to placebo and not superiority to existing – and usually much cheaper – medications. Our subscription to Epocrates informs us that a 1-month supply of once-a-day brand-name Abilify, Invega, or Latuda is more than $1,000.⁵ Alternatively, a 1-month supply of generic olanzapine, risperidone, or quetiapine is available for $4 at Walmart.⁶ As famously described in the CATIE trial⁷ of patients with schizophrenia, newer antipsychotics are not particularly better than older ones. In addition, a more recent meta-analysis⁸ did not find significant differences among antipsychotics’ efficacy.

A similar analysis can be made of antidepressants without addressing debates surrounding the effectiveness of antidepressants as a class and the value of psychological interventions over chemical ones. Reviews of the literature do not suggest that newer antidepressants are more effective than older ones. A recent meta-analysis of antidepressant efficacy did not find significant differences among antidepressants and, when looking at trends, amitriptyline, a much older antidepressant, was most effective.9

The most surprising part of the APA medical director’s statement was the claim of reduced suicidality. While lithium and clozapine have some evidence for reducing the risk of suicide, the evidence that antidepressants reduce suicide is equivocal. Quite the contrary, some evidence exists that antidepressants may increase the risk of suicide,¹⁰ and we are not aware of evidence suggesting that any newer agents can reduce suicide at any higher rate. One psychiatrist has even made a career out of testifying that antidepressants increase impulsivity and suicide.¹¹

We are not politicians, and we trust the APA to have good intentions with a desire to help patients suffering from mental illness. We understand the need to advocate for any measure that provides additional resources for the treatment of mental illness. We have no doubt that a publicly funded and appropriately regulated mental health system is a wise goal from both an ethical as well as a societal perspective. The APA has an imperative to advocate for our patients with the goal to improve our society.

However, we are concerned when our field makes unfounded claims. Advocating that insurance companies and the government provide most psychotropics without prior authorization and without discrimination does not appear to be based on scientific evidence and has serious economic implications that are not being weighed in a transparent manner. Whatever funding levels the APA recommends for the treatment of mental illness, said treatments will remain a limited resource, and then it becomes a question not just of ethics but of economics. What combination of resources produce the most benefit for the most people in question? Would the increased cost of a newer psychotropic be better spent on a system with more elaborate psychosocial interventions? In making this argument, does one risk repeating the historical blunder made when, in the 1960s, long-term psychiatric hospitals were closed with the intention of replacing their costs with outpatient treatments that then never materialized?

A review of the literature does not support the claim that newer psychotropic agents are more effective from either a clinical or an economic perspective. Cost-saving measures are ethical and possibly beneficial if they permit a more justifiable allocation of resources.



Dr. Lehman is an associate professor of psychiatry at the University of California, San Diego. He is codirector of all acute and intensive psychiatric treatment at the Veterans Affairs Medical Center in San Diego, where he practices clinical psychiatry. He is also the course director for the UCSD third-year medical student psychiatry clerkship. Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. Among his writings is Chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Cham, Switzerland: Springer, 2019).
 

References

1. Ann Med Psychol (Paris). 1952 Jun;110(2 1):112-7.

2. https://psychnews.psychiatryonline.org/doi/10.1176/appi.pn.2019.3b26.

3. Am J Emerg Med. 2016 Feb;34(2):133-9.

4. Eur Psychiatry. 2018 Feb;48:6-12.

5. https://online.epocrates.com/drugs. Retrieved March 3, 2019.

6. https://www.walmart.com/cp/$4-prescriptions/1078664. Retrieved March 27, 2019.

7. N Engl J Med. 2005 Sep 22;353(12):1209-23.

8. Am J Psychiatry. 2017. 174(10):927-42.

9. Lancet. 2018 Apr 7. 391(10128):P1357-66.

10. BMJ. 2009.339;b2880.

11. https://breggin.com/.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?

Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.

Study Design: Randomized, open-label, multicenter pilot trial.

Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.

Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.

Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.

Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.

Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?

Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.

Study Design: Randomized, open-label, multicenter pilot trial.

Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.

Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.

Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.

Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.

Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: Is an oral direct factor Xa inhibitor an effective alternative to low-molecular-weight heparin (LMWH) in treating cancer related venous thromboembolism (VTE)?

Background: LMWH has been the standard of care for treatment in patients with VTE and cancer. A newer class of drug, the direct factor Xa inhibitors, have been shown to be noninferior to vitamin K antagonists (VKAs) in treatment of VTE in noncancer patients, but little is known about their use in patients with cancer.

Study Design: Randomized, open-label, multicenter pilot trial.

Setting: United Kingdom; patients were recruited through the Clinical Trials Unit at the University of Warwick, Coventry.

Synopsis: The authors randomly assigned 406 cancer patients with diagnosed VTE either to the LMWH group or to the oral direct factor Xa inhibitor group to evaluate the primary endpoint of VTE reoccurrence and secondary endpoints of major bleeding or clinically relevant but not major bleeding (CRNMB). Rivaroxaban was noninferior to dalteparin in preventing VTE reoccurrence, with a 6-month VTE reoccurrence rate for dalteparin of 11% (95% confidence interval, 7%-16%) and a reoccurrence rate of 6% for rivaroxaban (95% CI, 2%-9%). Rates of major bleeding events were similar, although patients with esophageal or gastroesophageal cancers tended to experience more major bleeds with rivaroxaban than with dalteparin (4 of 11 vs. 1 of 19). CRNMB was 4% for dalteparin and 13% for rivaroxaban (hazard ratio, 3.76; 95% CI, 1.64-8.69). Limitations include slow recruitment, high mortality rate, and the treatment length being only 6 months.

Bottom line: In this small study, rivaroxaban was equally effective at reducing the rate of reoccurrence of cancer related VTE at 6 months but had higher rates of CRNMB. Patients with GI cancers may be at higher risk for major GI bleeding with rivaroxaban.

Citation: Young AM et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36(20):2017-23.

Dr. Marten is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

During 1995-2015, there was a 92% increase in the rate of foreign-body ingestions among children younger than 6 years – from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R² = 0.90; P less than .001) – according to an analysis in Pediatrics.

Deepak Sethi/iStock/Getty Images

The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.

The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).

The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.

The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.

Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.

SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.

During 1995-2015, there was a 92% increase in the rate of foreign-body ingestions among children younger than 6 years – from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R² = 0.90; P less than .001) – according to an analysis in Pediatrics.

Deepak Sethi/iStock/Getty Images

The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.

The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).

The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.

The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.

Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.

SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.

During 1995-2015, there was a 92% increase in the rate of foreign-body ingestions among children younger than 6 years – from an estimated 9 cases per 10,000 children to 18 cases per 10,000 (R² = 0.90; P less than .001) – according to an analysis in Pediatrics.

Deepak Sethi/iStock/Getty Images

The analysis was conducted by Danielle Orsagh-Yentis, MD, of Vanderbilt University, Nashville, Tenn., and her colleagues. They estimated that, during the study period, 759,074 children younger than 6 years of age were evaluated in U.S. EDs for suspected or confirmed foreign-body ingestions. These estimates were based on data for 29,893 actual cases taken from the National Electronic Injury Surveillance System (NEISS), which represents about 100 hospitals. Each case in this system is given a sample weight by the Consumer Product Safety Commission using a validated method, and the estimates are based on this weighting.

The analysis showed that children aged 1 year (21%) and boys (53%) were the most likely to ingest foreign bodies. Coins were the most frequently ingested objects, at 62%. Among cases which had the location noted (59%), most ingestions occurred in the home (97%).

The authors noted that, although batteries and magnets represented only 7% and 2% of all cases, respectively, “they can both enact considerable damage when ingested.” For example, despite being only the fourth mostly likely object to be ingested, batteries were the second mostly likely to be implicated among hospitalized patients.

The authors noted that the NEISS captures patients in the ED only; the total number of foreign-body ingestions, then, was likely underestimated. Despite this, the authors felt the long study period and large sample were strengths of their analysis.

Dr. Orsagh-Yentis and her associates disclosed no potential conflicts of interest.

SOURCE: Orsagh-Yentis D et al. Pediatrics. 2019 Apr 12. doi: 10.1542/peds.2018-1988.

PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.

Andrew S. Bowser/MDedge News

This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.

“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.

“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.

As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.

“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.

The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.

Dr. Paauw further supported his suggestions by describing two relevant studies.

In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.

In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.

Dr. Paauw had no relevant disclosures.

SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.

PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.

Andrew S. Bowser/MDedge News

This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.

“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.

“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.

As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.

“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.

The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.

Dr. Paauw further supported his suggestions by describing two relevant studies.

In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.

In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.

Dr. Paauw had no relevant disclosures.

SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.

PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.

Andrew S. Bowser/MDedge News

This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.

“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.

“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.

As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.

“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.

The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.

Dr. Paauw further supported his suggestions by describing two relevant studies.

In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.

In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.

Dr. Paauw had no relevant disclosures.

SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.

The Food and Drug Administration has issued a safety labeling change for flibanserin (Addyi), a treatment for premenopausal women with acquired, generalized hypoactive sexual desire disorder, according to a press release issued April 11 by the agency. The warning now says women should avoid consuming alcohol within 2 hours of taking flibanserin to avoid possible instances of severe hypotension and syncope. Previously, the warning said women should abstain from alcohol entirely.

According to the release, the manufacturer, Sprout, had hoped the FDA would remove the boxed warning and contraindication entirely. However, based on a review of two postmarket research studies, the agency chose to order these modifications to the warnings instead.

The first postmarket study was missing information related to participants’ blood pressure, which FDA officials thought was critical in determining risk; it appeared that this resulted from safety precautions built into the trial. The concern was that not only did this absent information provide further evidence of an interaction but that women at home would not have the benefit of these safety precautions and could suffer serious outcomes, including falls, accidents, and bodily harm. The other postmarketing trial showed that delaying administration of flibanserin until at least 2 hours after consuming alcohol reduced the risk of serious hypotension and syncope.

It is recommended that flibanserin be taken at bedtime because of risks associated with hypotension and syncope, as well as risks associated with central nervous system depression (such as sleepiness). Furthermore, patients are encouraged to discontinue treatment with flibanserin if their hypoactive sexual desire disorder does not improve after 8 weeks. The most common adverse reactions include dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth.

Full prescribing information is available on the FDA website, as is the full release regarding these safety label modifications.

[email protected]

The Food and Drug Administration has issued a safety labeling change for flibanserin (Addyi), a treatment for premenopausal women with acquired, generalized hypoactive sexual desire disorder, according to a press release issued April 11 by the agency. The warning now says women should avoid consuming alcohol within 2 hours of taking flibanserin to avoid possible instances of severe hypotension and syncope. Previously, the warning said women should abstain from alcohol entirely.

According to the release, the manufacturer, Sprout, had hoped the FDA would remove the boxed warning and contraindication entirely. However, based on a review of two postmarket research studies, the agency chose to order these modifications to the warnings instead.

The first postmarket study was missing information related to participants’ blood pressure, which FDA officials thought was critical in determining risk; it appeared that this resulted from safety precautions built into the trial. The concern was that not only did this absent information provide further evidence of an interaction but that women at home would not have the benefit of these safety precautions and could suffer serious outcomes, including falls, accidents, and bodily harm. The other postmarketing trial showed that delaying administration of flibanserin until at least 2 hours after consuming alcohol reduced the risk of serious hypotension and syncope.

It is recommended that flibanserin be taken at bedtime because of risks associated with hypotension and syncope, as well as risks associated with central nervous system depression (such as sleepiness). Furthermore, patients are encouraged to discontinue treatment with flibanserin if their hypoactive sexual desire disorder does not improve after 8 weeks. The most common adverse reactions include dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth.

Full prescribing information is available on the FDA website, as is the full release regarding these safety label modifications.

[email protected]

The Food and Drug Administration has issued a safety labeling change for flibanserin (Addyi), a treatment for premenopausal women with acquired, generalized hypoactive sexual desire disorder, according to a press release issued April 11 by the agency. The warning now says women should avoid consuming alcohol within 2 hours of taking flibanserin to avoid possible instances of severe hypotension and syncope. Previously, the warning said women should abstain from alcohol entirely.

According to the release, the manufacturer, Sprout, had hoped the FDA would remove the boxed warning and contraindication entirely. However, based on a review of two postmarket research studies, the agency chose to order these modifications to the warnings instead.

The first postmarket study was missing information related to participants’ blood pressure, which FDA officials thought was critical in determining risk; it appeared that this resulted from safety precautions built into the trial. The concern was that not only did this absent information provide further evidence of an interaction but that women at home would not have the benefit of these safety precautions and could suffer serious outcomes, including falls, accidents, and bodily harm. The other postmarketing trial showed that delaying administration of flibanserin until at least 2 hours after consuming alcohol reduced the risk of serious hypotension and syncope.

It is recommended that flibanserin be taken at bedtime because of risks associated with hypotension and syncope, as well as risks associated with central nervous system depression (such as sleepiness). Furthermore, patients are encouraged to discontinue treatment with flibanserin if their hypoactive sexual desire disorder does not improve after 8 weeks. The most common adverse reactions include dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth.

Full prescribing information is available on the FDA website, as is the full release regarding these safety label modifications.

[email protected]

As Democratic presidential primary candidates try to walk a political tightrope between the party’s progressive and center-left wings, they face increasing pressure to outline the details of their health reform proposals.

On April 10, Sen. Bernie Sanders (I-Vt.) reaffirmed his stance by reintroducing a Medicare-for-all bill, the idea that fueled his 2016 presidential run.

As with its previous iterations, Sen. Sanders’s latest bill would establish a national single-payer Medicare system with vastly expanded benefits, prohibit private plans from competing with Medicare, and eliminate cost sharing. New in this version is a universal provision for long-term care in home and community settings (but Medicaid would continue to cover institutional care).

Already, it has an impressive list of Senate cosponsors – including Sen. Sanders’s rivals for the Democratic presidential nomination, Cory Booker (D-N.J.), Kirsten Gillibrand (D-N.Y.), Kamala Harris (D-Calif.), and Elizabeth Warren (D-Mass.).

But many of the candidates – even official Medicare-for-all cosponsors – are at the same time edging toward a more incremental approach, called “Medicare for America.” Proponents argue it could deliver better health care to Americans while avoiding political, budgetary, and legal objections.

It comes as politicians tread carefully over the political land mines a Medicare-for-all endorsement could unleash, while seeking to capitalize on a growing appetite for health reform.

During the 2018 midterm election campaigns, some congressional candidates talked about allowing people older than 55 years to join Medicare, or allowing people younger than 65 years to buy into it if they choose (the “public option”). Many aren’t eager to face the industry opposition that a full-on Medicare expansion would surely trigger.

From the consumer perspective, sweeping reform poses a risk. Despite Medicare’s popularity with its beneficiaries, the majority of Americans express satisfaction with their health care, and many are nervous about giving up private options. Also, many analysts are worried that a generous Medicare-for-all plan that promises everything would break the bank without any patient payments.

That tension is pushing a number of candidates toward the emerging Medicare for America option. The bill was introduced last December to little fanfare by two Democrats, Rep. Rosa DeLauro of Connecticut and Rep. Jan Schakowsky of Illinois. It hasn’t been reintroduced in the new Congress.

This proposed system would guarantee universal coverage, but leaves job-based insurance available for those who want it. Unlike Medicare-for-all, though, it preserves premiums and deductibles, so beneficiaries would still have to pay some out-of-pocket costs. It allows private insurers to operate Medicare plans as well, a system called Medicare Advantage that covers about a third of the program’s beneficiaries currently, and which would be outlawed under Medicare-for-all.

“Before policies get defined, what you see is people endorsing a plan that is a little, perhaps, less subject to early attack,” said Celinda Lake, a Democratic pollster. “A lot of candidates feel if they endorse a plan that leaves some private insurance, they get more time to say what their ideas are about.”

Medicare for America got its first high-profile endorsement from former Texas Rep. Beto O’Rourke, who launched his own 2020 bid in mid-March. Other candidates – including Sen. Warren, Sen. Gillibrand, and Pete Buttigieg, the mayor of South Bend, Ind. – have tiptoed toward it without making any endorsements, suggesting they back Medicare-for-all in theory but also support a system that retains private insurance, at least temporarily.

Such an approach is perhaps unsurprising. Polling indicates voters want strong health reform. Candidates, election experts say, need something powerful to deliver.

Improving the Affordable Care Act, an idea backed by Sen. Amy Klobuchar (D-Minn.) who is running in the presidential primary’s moderate lane, may not suffice.

“The ACA is popular at the 50% level, but it’s not energetic. It doesn’t get people who really like it,” said Bob Blendon, a political analyst at the Harvard T.H. Chan School of Public Health. “What they’re looking for is something that is exciting but isn’t threatening.”

Both Medicare-for-all and Medicare for America, experts noted, offer something that presidential candidates can campaign on and a health alternative that at first blush sounds appealing to many. But the latter could skirt some potential obstacles.

Approval for Medicare-for-all drops when people learn that, under such a program, they would likely lose their current health plan (even if the government-offered plan could theoretically provide more generous coverage).

The cost-sharing element of Medicare for America, meanwhile, would ostensibly quiet some of the concerns about paying for Medicare’s expansion, though critics on the left worry it would mean some people would still be unable to afford care.

This also tracks with recent polling suggesting that, while Medicare-for-all support can be swayed, voters of all political stripes favor some sort of way to extend optional Medicare coverage, without necessarily eliminating the private industry altogether.

Employers would have to offer plans that were at least as generous as the government program, or direct employees to Medicare. Employers who stop offering health benefits would have to pay a Medicare payroll tax.

For now, most candidates are still avoiding a concrete stance on Medicare for America. Despite signs of interest, the campaigns of Mr. Buttigieg, Sen. Gillibrand, and Sen. Warren all declined to directly answer questions about whether they endorse Medicare for America. The campaigns of other Democratic candidates in the race – Sen. Harris, Sen. Klobuchar, Sen. Booker, and former Housing and Urban Development Secretary Julian Castro and Washington Gov. Jay Inslee – similarly declined to comment.

Reading between the lines, though, their promises to achieve universal health care by expanding Medicare – while retaining private insurance – leaves them few options besides something like Medicare for America, argued one of its main architects.

“There are variations besides this particular plan, but once you start to actually dig into this, if you want universal coverage you’re going to have to do the kinds of things” spelled out in Medicare for America, argued Jacob Hacker, a political scientist at Yale University, who played a lead role in devising this proposal.

Still, though, it has prompted objections from both the left and the right.

On the far left, the cost sharing is a dominant concern. (Under Medicare for America, an individual would have a $3,500 out-of-pocket limit; a family would have a $5,000 limit. Premiums would be capped at almost 10% of a household’s income.) Those critics also say the plan’s accommodations to private insurance limit the government’s ability to negotiate lower prices.

Conservatives repeat many of the arguments levied against Medicare-for-all – too expensive and too disruptive.

Hospitals, insurance, drugmakers, and doctors, who have already mobilized against Medicare-for-all, also can be expected to make just as strong a showing against Medicare for America, political analysts said. More Medicare means less revenue for the medical industry.

Said David Blumenthal of the Commonwealth Fund: “The fact of expanded Medicare will be the focus of attacks.”
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

As Democratic presidential primary candidates try to walk a political tightrope between the party’s progressive and center-left wings, they face increasing pressure to outline the details of their health reform proposals.

On April 10, Sen. Bernie Sanders (I-Vt.) reaffirmed his stance by reintroducing a Medicare-for-all bill, the idea that fueled his 2016 presidential run.

As with its previous iterations, Sen. Sanders’s latest bill would establish a national single-payer Medicare system with vastly expanded benefits, prohibit private plans from competing with Medicare, and eliminate cost sharing. New in this version is a universal provision for long-term care in home and community settings (but Medicaid would continue to cover institutional care).

Already, it has an impressive list of Senate cosponsors – including Sen. Sanders’s rivals for the Democratic presidential nomination, Cory Booker (D-N.J.), Kirsten Gillibrand (D-N.Y.), Kamala Harris (D-Calif.), and Elizabeth Warren (D-Mass.).

But many of the candidates – even official Medicare-for-all cosponsors – are at the same time edging toward a more incremental approach, called “Medicare for America.” Proponents argue it could deliver better health care to Americans while avoiding political, budgetary, and legal objections.

It comes as politicians tread carefully over the political land mines a Medicare-for-all endorsement could unleash, while seeking to capitalize on a growing appetite for health reform.

During the 2018 midterm election campaigns, some congressional candidates talked about allowing people older than 55 years to join Medicare, or allowing people younger than 65 years to buy into it if they choose (the “public option”). Many aren’t eager to face the industry opposition that a full-on Medicare expansion would surely trigger.

From the consumer perspective, sweeping reform poses a risk. Despite Medicare’s popularity with its beneficiaries, the majority of Americans express satisfaction with their health care, and many are nervous about giving up private options. Also, many analysts are worried that a generous Medicare-for-all plan that promises everything would break the bank without any patient payments.

That tension is pushing a number of candidates toward the emerging Medicare for America option. The bill was introduced last December to little fanfare by two Democrats, Rep. Rosa DeLauro of Connecticut and Rep. Jan Schakowsky of Illinois. It hasn’t been reintroduced in the new Congress.

This proposed system would guarantee universal coverage, but leaves job-based insurance available for those who want it. Unlike Medicare-for-all, though, it preserves premiums and deductibles, so beneficiaries would still have to pay some out-of-pocket costs. It allows private insurers to operate Medicare plans as well, a system called Medicare Advantage that covers about a third of the program’s beneficiaries currently, and which would be outlawed under Medicare-for-all.

“Before policies get defined, what you see is people endorsing a plan that is a little, perhaps, less subject to early attack,” said Celinda Lake, a Democratic pollster. “A lot of candidates feel if they endorse a plan that leaves some private insurance, they get more time to say what their ideas are about.”

Medicare for America got its first high-profile endorsement from former Texas Rep. Beto O’Rourke, who launched his own 2020 bid in mid-March. Other candidates – including Sen. Warren, Sen. Gillibrand, and Pete Buttigieg, the mayor of South Bend, Ind. – have tiptoed toward it without making any endorsements, suggesting they back Medicare-for-all in theory but also support a system that retains private insurance, at least temporarily.

Such an approach is perhaps unsurprising. Polling indicates voters want strong health reform. Candidates, election experts say, need something powerful to deliver.

Improving the Affordable Care Act, an idea backed by Sen. Amy Klobuchar (D-Minn.) who is running in the presidential primary’s moderate lane, may not suffice.

“The ACA is popular at the 50% level, but it’s not energetic. It doesn’t get people who really like it,” said Bob Blendon, a political analyst at the Harvard T.H. Chan School of Public Health. “What they’re looking for is something that is exciting but isn’t threatening.”

Both Medicare-for-all and Medicare for America, experts noted, offer something that presidential candidates can campaign on and a health alternative that at first blush sounds appealing to many. But the latter could skirt some potential obstacles.

Approval for Medicare-for-all drops when people learn that, under such a program, they would likely lose their current health plan (even if the government-offered plan could theoretically provide more generous coverage).

The cost-sharing element of Medicare for America, meanwhile, would ostensibly quiet some of the concerns about paying for Medicare’s expansion, though critics on the left worry it would mean some people would still be unable to afford care.

This also tracks with recent polling suggesting that, while Medicare-for-all support can be swayed, voters of all political stripes favor some sort of way to extend optional Medicare coverage, without necessarily eliminating the private industry altogether.

Employers would have to offer plans that were at least as generous as the government program, or direct employees to Medicare. Employers who stop offering health benefits would have to pay a Medicare payroll tax.

For now, most candidates are still avoiding a concrete stance on Medicare for America. Despite signs of interest, the campaigns of Mr. Buttigieg, Sen. Gillibrand, and Sen. Warren all declined to directly answer questions about whether they endorse Medicare for America. The campaigns of other Democratic candidates in the race – Sen. Harris, Sen. Klobuchar, Sen. Booker, and former Housing and Urban Development Secretary Julian Castro and Washington Gov. Jay Inslee – similarly declined to comment.

Reading between the lines, though, their promises to achieve universal health care by expanding Medicare – while retaining private insurance – leaves them few options besides something like Medicare for America, argued one of its main architects.

“There are variations besides this particular plan, but once you start to actually dig into this, if you want universal coverage you’re going to have to do the kinds of things” spelled out in Medicare for America, argued Jacob Hacker, a political scientist at Yale University, who played a lead role in devising this proposal.

Still, though, it has prompted objections from both the left and the right.

On the far left, the cost sharing is a dominant concern. (Under Medicare for America, an individual would have a $3,500 out-of-pocket limit; a family would have a $5,000 limit. Premiums would be capped at almost 10% of a household’s income.) Those critics also say the plan’s accommodations to private insurance limit the government’s ability to negotiate lower prices.

Conservatives repeat many of the arguments levied against Medicare-for-all – too expensive and too disruptive.

Hospitals, insurance, drugmakers, and doctors, who have already mobilized against Medicare-for-all, also can be expected to make just as strong a showing against Medicare for America, political analysts said. More Medicare means less revenue for the medical industry.

Said David Blumenthal of the Commonwealth Fund: “The fact of expanded Medicare will be the focus of attacks.”
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

As Democratic presidential primary candidates try to walk a political tightrope between the party’s progressive and center-left wings, they face increasing pressure to outline the details of their health reform proposals.

On April 10, Sen. Bernie Sanders (I-Vt.) reaffirmed his stance by reintroducing a Medicare-for-all bill, the idea that fueled his 2016 presidential run.

As with its previous iterations, Sen. Sanders’s latest bill would establish a national single-payer Medicare system with vastly expanded benefits, prohibit private plans from competing with Medicare, and eliminate cost sharing. New in this version is a universal provision for long-term care in home and community settings (but Medicaid would continue to cover institutional care).

Already, it has an impressive list of Senate cosponsors – including Sen. Sanders’s rivals for the Democratic presidential nomination, Cory Booker (D-N.J.), Kirsten Gillibrand (D-N.Y.), Kamala Harris (D-Calif.), and Elizabeth Warren (D-Mass.).

But many of the candidates – even official Medicare-for-all cosponsors – are at the same time edging toward a more incremental approach, called “Medicare for America.” Proponents argue it could deliver better health care to Americans while avoiding political, budgetary, and legal objections.

It comes as politicians tread carefully over the political land mines a Medicare-for-all endorsement could unleash, while seeking to capitalize on a growing appetite for health reform.

During the 2018 midterm election campaigns, some congressional candidates talked about allowing people older than 55 years to join Medicare, or allowing people younger than 65 years to buy into it if they choose (the “public option”). Many aren’t eager to face the industry opposition that a full-on Medicare expansion would surely trigger.

From the consumer perspective, sweeping reform poses a risk. Despite Medicare’s popularity with its beneficiaries, the majority of Americans express satisfaction with their health care, and many are nervous about giving up private options. Also, many analysts are worried that a generous Medicare-for-all plan that promises everything would break the bank without any patient payments.

That tension is pushing a number of candidates toward the emerging Medicare for America option. The bill was introduced last December to little fanfare by two Democrats, Rep. Rosa DeLauro of Connecticut and Rep. Jan Schakowsky of Illinois. It hasn’t been reintroduced in the new Congress.

This proposed system would guarantee universal coverage, but leaves job-based insurance available for those who want it. Unlike Medicare-for-all, though, it preserves premiums and deductibles, so beneficiaries would still have to pay some out-of-pocket costs. It allows private insurers to operate Medicare plans as well, a system called Medicare Advantage that covers about a third of the program’s beneficiaries currently, and which would be outlawed under Medicare-for-all.

“Before policies get defined, what you see is people endorsing a plan that is a little, perhaps, less subject to early attack,” said Celinda Lake, a Democratic pollster. “A lot of candidates feel if they endorse a plan that leaves some private insurance, they get more time to say what their ideas are about.”

Medicare for America got its first high-profile endorsement from former Texas Rep. Beto O’Rourke, who launched his own 2020 bid in mid-March. Other candidates – including Sen. Warren, Sen. Gillibrand, and Pete Buttigieg, the mayor of South Bend, Ind. – have tiptoed toward it without making any endorsements, suggesting they back Medicare-for-all in theory but also support a system that retains private insurance, at least temporarily.

Such an approach is perhaps unsurprising. Polling indicates voters want strong health reform. Candidates, election experts say, need something powerful to deliver.

Improving the Affordable Care Act, an idea backed by Sen. Amy Klobuchar (D-Minn.) who is running in the presidential primary’s moderate lane, may not suffice.

“The ACA is popular at the 50% level, but it’s not energetic. It doesn’t get people who really like it,” said Bob Blendon, a political analyst at the Harvard T.H. Chan School of Public Health. “What they’re looking for is something that is exciting but isn’t threatening.”

Both Medicare-for-all and Medicare for America, experts noted, offer something that presidential candidates can campaign on and a health alternative that at first blush sounds appealing to many. But the latter could skirt some potential obstacles.

Approval for Medicare-for-all drops when people learn that, under such a program, they would likely lose their current health plan (even if the government-offered plan could theoretically provide more generous coverage).

The cost-sharing element of Medicare for America, meanwhile, would ostensibly quiet some of the concerns about paying for Medicare’s expansion, though critics on the left worry it would mean some people would still be unable to afford care.

This also tracks with recent polling suggesting that, while Medicare-for-all support can be swayed, voters of all political stripes favor some sort of way to extend optional Medicare coverage, without necessarily eliminating the private industry altogether.

Employers would have to offer plans that were at least as generous as the government program, or direct employees to Medicare. Employers who stop offering health benefits would have to pay a Medicare payroll tax.

For now, most candidates are still avoiding a concrete stance on Medicare for America. Despite signs of interest, the campaigns of Mr. Buttigieg, Sen. Gillibrand, and Sen. Warren all declined to directly answer questions about whether they endorse Medicare for America. The campaigns of other Democratic candidates in the race – Sen. Harris, Sen. Klobuchar, Sen. Booker, and former Housing and Urban Development Secretary Julian Castro and Washington Gov. Jay Inslee – similarly declined to comment.

Reading between the lines, though, their promises to achieve universal health care by expanding Medicare – while retaining private insurance – leaves them few options besides something like Medicare for America, argued one of its main architects.

“There are variations besides this particular plan, but once you start to actually dig into this, if you want universal coverage you’re going to have to do the kinds of things” spelled out in Medicare for America, argued Jacob Hacker, a political scientist at Yale University, who played a lead role in devising this proposal.

Still, though, it has prompted objections from both the left and the right.

On the far left, the cost sharing is a dominant concern. (Under Medicare for America, an individual would have a $3,500 out-of-pocket limit; a family would have a $5,000 limit. Premiums would be capped at almost 10% of a household’s income.) Those critics also say the plan’s accommodations to private insurance limit the government’s ability to negotiate lower prices.

Conservatives repeat many of the arguments levied against Medicare-for-all – too expensive and too disruptive.

Hospitals, insurance, drugmakers, and doctors, who have already mobilized against Medicare-for-all, also can be expected to make just as strong a showing against Medicare for America, political analysts said. More Medicare means less revenue for the medical industry.

Said David Blumenthal of the Commonwealth Fund: “The fact of expanded Medicare will be the focus of attacks.”
 

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

DALLAS – Neurologists soon may use a blood biomarker of axonal damage to monitor patients with multiple sclerosis (MS) and guide treatment decisions, according to a lecture delivered at ACTRIMS Forum 2019.

Physicians have lacked biomarkers to assess subclinical MS disease activity, but technological advances and recently published data suggest that blood levels of neurofilament light chain (NfL) will help fill that gap, said David Leppert, MD, senior research associate in the department of neurology at University Hopsital Basel (Switzerland).

Among patients with MS, blood NfL levels predict disability, brain volume loss, and spinal cord atrophy. In addition, studies have found that blood NfL decreases in response to disease-modifying therapy (DMT) and that second-line DMTs may decrease blood NfL more than first-line DMTs do.

The establishment of normative databases and reference biomarkers may allow neurologists to use NfL in their care of individual patients, Dr. Leppert predicted at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “I am very positive that we will make a breakthrough in the next 2 or 3 years for an individual use of neurofilaments,” he said.
 

Response to DMT

An analysis of blood NfL levels from patients with MS and from healthy controls in two phase 3 trials of fingolimod, FREEDOMS and TRANSFORMS, provides insights into NfL’s response to DMT (Neurology. 2019 Mar 5;92[10]:e1007-15). In FREEDOMS, which compared fingolimod with placebo, “fingolimod leads to a rapid decrease of neurofilament levels, close to normality, while placebo patients continue to have high levels,” said Dr. Leppert, a coauthor of the study.

TRANSFORMS compared interferon-beta and fingolimod. “The clinical experience that fingolimod is a more potent compound than interferon is actually reflected here by the NfL results,” Dr. Leppert said. “Both compounds lead to a decrease of neurofilaments – so, a decrease of neuronal damage – but one drug is more potent than the other one.”

Similarly, data from the observational EPIC study indicate that patients who do not receive DMT have a consistent increase in NfL levels, whereas those who receive platform therapies have a slight decrease in NfL and those who receive second-line therapies have a greater decrease, Dr. Leppert said.


 

Decades of research

For about 20 years, researchers have studied neurofilaments in cerebrospinal fluid (CSF) as a potential biomarker for MS and other diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and head trauma.

“What prevented the emergence of NfL to clinical practice was the inability to measure it in blood because levels are 50-100 times lower [in blood] than in CSF,” Dr. Leppert said.

The development of single molecule array (SIMOA) technology enabled researchers to show a proper correlation between levels of NfL in CSF and those in blood, Dr. Leppert said. “That is now allowing repetitive testing in an accessible fluid compartment, meaning serum or plasma,” he said.

Compared with brain MRI, NfL may provide novel insights into MS disease activity. “MRI is measuring a structural deficit of the past,” Dr. Leppert said. “NfL is measuring online, real time what axonal damage is occurring.”
 

Correlation with outcomes

At the group level, patients with MS have higher levels of NfL, compared with controls, and levels are higher in patients with progressive forms of MS versus relapsing forms. “Levels increase dramatically in the wake of relapse,” he said.

Barro et al. found that patients with higher serum levels of NfL are more likely to experience Expanded Disability Status Scale (EDSS) worsening (Brain. 2018 Aug 1;141[8]:2382-91). Furthermore, MRI lesions are independently associated with serum NfL, and patients with higher levels of serum NfL have significantly greater average loss in brain volume and spinal cord volume over 5 years.
 

A treatment algorithm

NfL someday could be incorporated into MS treatment algorithms, Dr. Leppert suggested. For instance, if a patient has high levels of disease activity based on MRI or clinical grounds, then prescribe a high-efficacy therapy. If not, measure NfL. “If the levels are low, then you can be assured to use platform therapies or continue what the patient has. But if NfL levels are high, then you should choose high efficacious therapies or switch to high-efficacious therapies in the long run,” he said.

Limitations and next steps

Although NfL is a specific marker of neuronal damage, it is not specific for the cause of the damage. Further studies are needed to better understand NfL metabolism and confounding factors such as age. Reference biomarkers likely will be needed “to conceptualize whether the signal of NfL is due to acute disease or chronic disease,” Dr. Leppert said.

“We need to optimize the assay and come to a worldwide agreement on the platform. We need to have prospective studies, mainly to achieve regulatory acceptance. And we need to have a normative database” to determine which NfL values are pathologic at a particular age, he said.

Despite the biomarker’s potential, blood NfL levels will not replace clinical expertise. “Biomarkers cannot be of value without a clinical backing and a clinical evaluation,” Dr. Leppert said. “The idea that this will replace us or any other person who makes a clinical judgment is a big error. NfL will prevail as a biomarker. ... But interpretation of the clinical background is germane.”

Dr. Leppert has been an employee of pharmaceutical companies, most recently Novartis.

[email protected]

DALLAS – Neurologists soon may use a blood biomarker of axonal damage to monitor patients with multiple sclerosis (MS) and guide treatment decisions, according to a lecture delivered at ACTRIMS Forum 2019.

Physicians have lacked biomarkers to assess subclinical MS disease activity, but technological advances and recently published data suggest that blood levels of neurofilament light chain (NfL) will help fill that gap, said David Leppert, MD, senior research associate in the department of neurology at University Hopsital Basel (Switzerland).

Among patients with MS, blood NfL levels predict disability, brain volume loss, and spinal cord atrophy. In addition, studies have found that blood NfL decreases in response to disease-modifying therapy (DMT) and that second-line DMTs may decrease blood NfL more than first-line DMTs do.

The establishment of normative databases and reference biomarkers may allow neurologists to use NfL in their care of individual patients, Dr. Leppert predicted at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “I am very positive that we will make a breakthrough in the next 2 or 3 years for an individual use of neurofilaments,” he said.
 

Response to DMT

An analysis of blood NfL levels from patients with MS and from healthy controls in two phase 3 trials of fingolimod, FREEDOMS and TRANSFORMS, provides insights into NfL’s response to DMT (Neurology. 2019 Mar 5;92[10]:e1007-15). In FREEDOMS, which compared fingolimod with placebo, “fingolimod leads to a rapid decrease of neurofilament levels, close to normality, while placebo patients continue to have high levels,” said Dr. Leppert, a coauthor of the study.

TRANSFORMS compared interferon-beta and fingolimod. “The clinical experience that fingolimod is a more potent compound than interferon is actually reflected here by the NfL results,” Dr. Leppert said. “Both compounds lead to a decrease of neurofilaments – so, a decrease of neuronal damage – but one drug is more potent than the other one.”

Similarly, data from the observational EPIC study indicate that patients who do not receive DMT have a consistent increase in NfL levels, whereas those who receive platform therapies have a slight decrease in NfL and those who receive second-line therapies have a greater decrease, Dr. Leppert said.


 

Decades of research

For about 20 years, researchers have studied neurofilaments in cerebrospinal fluid (CSF) as a potential biomarker for MS and other diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and head trauma.

“What prevented the emergence of NfL to clinical practice was the inability to measure it in blood because levels are 50-100 times lower [in blood] than in CSF,” Dr. Leppert said.

The development of single molecule array (SIMOA) technology enabled researchers to show a proper correlation between levels of NfL in CSF and those in blood, Dr. Leppert said. “That is now allowing repetitive testing in an accessible fluid compartment, meaning serum or plasma,” he said.

Compared with brain MRI, NfL may provide novel insights into MS disease activity. “MRI is measuring a structural deficit of the past,” Dr. Leppert said. “NfL is measuring online, real time what axonal damage is occurring.”
 

Correlation with outcomes

At the group level, patients with MS have higher levels of NfL, compared with controls, and levels are higher in patients with progressive forms of MS versus relapsing forms. “Levels increase dramatically in the wake of relapse,” he said.

Barro et al. found that patients with higher serum levels of NfL are more likely to experience Expanded Disability Status Scale (EDSS) worsening (Brain. 2018 Aug 1;141[8]:2382-91). Furthermore, MRI lesions are independently associated with serum NfL, and patients with higher levels of serum NfL have significantly greater average loss in brain volume and spinal cord volume over 5 years.
 

A treatment algorithm

NfL someday could be incorporated into MS treatment algorithms, Dr. Leppert suggested. For instance, if a patient has high levels of disease activity based on MRI or clinical grounds, then prescribe a high-efficacy therapy. If not, measure NfL. “If the levels are low, then you can be assured to use platform therapies or continue what the patient has. But if NfL levels are high, then you should choose high efficacious therapies or switch to high-efficacious therapies in the long run,” he said.

Limitations and next steps

Although NfL is a specific marker of neuronal damage, it is not specific for the cause of the damage. Further studies are needed to better understand NfL metabolism and confounding factors such as age. Reference biomarkers likely will be needed “to conceptualize whether the signal of NfL is due to acute disease or chronic disease,” Dr. Leppert said.

“We need to optimize the assay and come to a worldwide agreement on the platform. We need to have prospective studies, mainly to achieve regulatory acceptance. And we need to have a normative database” to determine which NfL values are pathologic at a particular age, he said.

Despite the biomarker’s potential, blood NfL levels will not replace clinical expertise. “Biomarkers cannot be of value without a clinical backing and a clinical evaluation,” Dr. Leppert said. “The idea that this will replace us or any other person who makes a clinical judgment is a big error. NfL will prevail as a biomarker. ... But interpretation of the clinical background is germane.”

Dr. Leppert has been an employee of pharmaceutical companies, most recently Novartis.

[email protected]

DALLAS – Neurologists soon may use a blood biomarker of axonal damage to monitor patients with multiple sclerosis (MS) and guide treatment decisions, according to a lecture delivered at ACTRIMS Forum 2019.

Physicians have lacked biomarkers to assess subclinical MS disease activity, but technological advances and recently published data suggest that blood levels of neurofilament light chain (NfL) will help fill that gap, said David Leppert, MD, senior research associate in the department of neurology at University Hopsital Basel (Switzerland).

Among patients with MS, blood NfL levels predict disability, brain volume loss, and spinal cord atrophy. In addition, studies have found that blood NfL decreases in response to disease-modifying therapy (DMT) and that second-line DMTs may decrease blood NfL more than first-line DMTs do.

The establishment of normative databases and reference biomarkers may allow neurologists to use NfL in their care of individual patients, Dr. Leppert predicted at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “I am very positive that we will make a breakthrough in the next 2 or 3 years for an individual use of neurofilaments,” he said.
 

Response to DMT

An analysis of blood NfL levels from patients with MS and from healthy controls in two phase 3 trials of fingolimod, FREEDOMS and TRANSFORMS, provides insights into NfL’s response to DMT (Neurology. 2019 Mar 5;92[10]:e1007-15). In FREEDOMS, which compared fingolimod with placebo, “fingolimod leads to a rapid decrease of neurofilament levels, close to normality, while placebo patients continue to have high levels,” said Dr. Leppert, a coauthor of the study.

TRANSFORMS compared interferon-beta and fingolimod. “The clinical experience that fingolimod is a more potent compound than interferon is actually reflected here by the NfL results,” Dr. Leppert said. “Both compounds lead to a decrease of neurofilaments – so, a decrease of neuronal damage – but one drug is more potent than the other one.”

Similarly, data from the observational EPIC study indicate that patients who do not receive DMT have a consistent increase in NfL levels, whereas those who receive platform therapies have a slight decrease in NfL and those who receive second-line therapies have a greater decrease, Dr. Leppert said.


 

Decades of research

For about 20 years, researchers have studied neurofilaments in cerebrospinal fluid (CSF) as a potential biomarker for MS and other diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and head trauma.

“What prevented the emergence of NfL to clinical practice was the inability to measure it in blood because levels are 50-100 times lower [in blood] than in CSF,” Dr. Leppert said.

The development of single molecule array (SIMOA) technology enabled researchers to show a proper correlation between levels of NfL in CSF and those in blood, Dr. Leppert said. “That is now allowing repetitive testing in an accessible fluid compartment, meaning serum or plasma,” he said.

Compared with brain MRI, NfL may provide novel insights into MS disease activity. “MRI is measuring a structural deficit of the past,” Dr. Leppert said. “NfL is measuring online, real time what axonal damage is occurring.”
 

Correlation with outcomes

At the group level, patients with MS have higher levels of NfL, compared with controls, and levels are higher in patients with progressive forms of MS versus relapsing forms. “Levels increase dramatically in the wake of relapse,” he said.

Barro et al. found that patients with higher serum levels of NfL are more likely to experience Expanded Disability Status Scale (EDSS) worsening (Brain. 2018 Aug 1;141[8]:2382-91). Furthermore, MRI lesions are independently associated with serum NfL, and patients with higher levels of serum NfL have significantly greater average loss in brain volume and spinal cord volume over 5 years.
 

A treatment algorithm

NfL someday could be incorporated into MS treatment algorithms, Dr. Leppert suggested. For instance, if a patient has high levels of disease activity based on MRI or clinical grounds, then prescribe a high-efficacy therapy. If not, measure NfL. “If the levels are low, then you can be assured to use platform therapies or continue what the patient has. But if NfL levels are high, then you should choose high efficacious therapies or switch to high-efficacious therapies in the long run,” he said.

Limitations and next steps

Although NfL is a specific marker of neuronal damage, it is not specific for the cause of the damage. Further studies are needed to better understand NfL metabolism and confounding factors such as age. Reference biomarkers likely will be needed “to conceptualize whether the signal of NfL is due to acute disease or chronic disease,” Dr. Leppert said.

“We need to optimize the assay and come to a worldwide agreement on the platform. We need to have prospective studies, mainly to achieve regulatory acceptance. And we need to have a normative database” to determine which NfL values are pathologic at a particular age, he said.

Despite the biomarker’s potential, blood NfL levels will not replace clinical expertise. “Biomarkers cannot be of value without a clinical backing and a clinical evaluation,” Dr. Leppert said. “The idea that this will replace us or any other person who makes a clinical judgment is a big error. NfL will prevail as a biomarker. ... But interpretation of the clinical background is germane.”

Dr. Leppert has been an employee of pharmaceutical companies, most recently Novartis.

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