The nation’s opioid epidemic has been called today’s version of the 1980s AIDS crisis.

In a New Hampshire speech on March 19, President Donald Trump pushed for a tougher federal response, emphasizing a tough-on-crime approach for drug dealers and more funding for treatment. And Congress is upping the ante, via a series of hearings – including one scheduled to last March 21-22 – to study legislation that might tackle the unyielding scourge, which has cost an estimated $1 trillion in premature deaths, health care costs, and lost wages since 2001.

Dr. Leana Wen, an emergency physician by training and the health commissioner for hard-hit Baltimore, said Capitol Hill has to help communities at risk of becoming overwhelmed.

“We haven’t seen the peak of the epidemic. We are seeing the numbers climb year after year,” she said.

Provisional data from the Centers for Disease Control and Prevention suggest that almost 45,000 Americans died from opioid overdoses in the 12-month period ending July 2017, up from about 38,000 in the previous cycle. (Those data are likely to change, since many death certificates have not yet been reported to the CDC.)

“It’s not going to get any better unless we take dramatic action,” Dr. Wen said.

And the time for most meaningful change could be dwindling. Advocates say what they need most is money, which would most likely come through the government spending bill that’s due March 23. But they aren’t holding their breath.

Show me the money

The federal budget deal, which was signed into law in early February, promised $6 billion over 2 years for initiatives to fight opioid abuse. Congress is still figuring out how to divvy up those funds. The blueprint is expected to be included in the spending bill this week.

In February, a bipartisan group of senators introduced a bill that would add another $1 billion in funding to support expanded treatment and also limit clinicians to prescribing no more than 3 days’ worth of opioids at a time.

That legislation is likely to have wide support in the Senate, but its path through the House is less certain.

This cash infusion is still not going to be enough, predicted Daniel Raymond, policy director for the Harm Reduction Coalition, a national organization that works on overdose prevention.

“It’s not clear whether there’s a real appetite to go as far as we need to see Congress go,” he said. “To have a fighting chance, we need a long-term commitment of at least $10 billion per year.” Academic experts said that assessment sounded on target.

The figure is more than 3 times what’s allocated in the budget and 10 times what even the new Senate bill would provide, and far beyond the spending levels put forth by any previous packages to fight the opioid epidemic.

The difficulty in getting funding – and a key reason why the bipartisan Senate bill might stall in the House – in part goes to the heart of Republicans’ philosophy about budgeting.

The GOP, which controls both chambers of Congress, has “always been very focused on pay-fors,” said a Republican aide to the House Energy and Commerce Committee, explaining that new funding is generally expected to be accompanied by cuts in current expenditures so that overall government spending doesn’t rise. And that could limit how much money lawmakers are ultimately willing to commit to fight opioid abuse.

Some observers worry this notion is pound-foolish.

“We have an enormous set of costs ahead of us if we don’t invest now,” said Dr. Traci Green, an associate professor of emergency medicine and community health science at Boston University, who has extensively researched the epidemic.

Ahead in Congress

Meanwhile, the House could take up its version of a separate Senate-passed proposal designed to, in certain cases, make more prominent any opioid history in a patient’s medical record. The idea is to prevent doctors from prescribing opioids to at-risk patients.

In addition, the House’s Energy and Commerce Committee in late February held a hearing focused on “enforcement” – discussing, for instance, giving the federal Drug Enforcement Administration more power in drug trafficking, and whether to treat fentanyl, a particularly potent synthetic opioid, as a controlled substance. The hearings March 21-22 will tackle a slew of public health–oriented bills, such as making sure overdose patients in the emergency room get appropriate medication and treatment upon discharge, or expanding access to buprenorphine, which is used to treat addiction.

And the House Ways and Means Committee, which has jurisdiction over Medicare – the federal insurance plan for seniors and disabled people – is working to develop strategies that limit access to opioids and make treatment more available.

These are some promising ideas, Mr. Raymond said, but it’s still “playing catch-up. … The big gap is the money, and the broader vision.”

This flurry of activity comes after Congress in 2016 passed two laws directly dealing with addiction and substance abuse disorders, the Comprehensive Addiction and Recovery Act and the 21st Century Cures Act. CARA promised $181 million – although it didn’t appropriate those dollars – while the Cures Act provided $1 billion over 2 years.

It’s playing out against the backdrop of steady policy tensions.

The Trump administration, which in October declared the opioid epidemic a public health crisis, has repeatedly pushed a more punitive approach, such as harsher sentences for drug trafficking, including the death penalty, and establishing mandatory minimum sentences. That emphasis, experts said, detracts from other parts of the plan that might highlight, say, addiction treatment.

Instead, those experts emphasized treatment and prevention as well as “harm reduction” ideas such as providing more overdose-antidote medication and funding programs like syringe exchanges.

They say focusing on punishment has been ineffective in the past and neglects the heart of the issue.

Certainly, curbing the flow of illegal drugs is important, Dr. Wen said. But it’s insufficient by itself. And the size of the problem means lawmakers need to provide quicker, more direct aid – not just proposals that tinker “around the edges.”

“We would never refuse any funding, because we need it desperately,” she said. “But ask us what we need.”

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

The nation’s opioid epidemic has been called today’s version of the 1980s AIDS crisis.

In a New Hampshire speech on March 19, President Donald Trump pushed for a tougher federal response, emphasizing a tough-on-crime approach for drug dealers and more funding for treatment. And Congress is upping the ante, via a series of hearings – including one scheduled to last March 21-22 – to study legislation that might tackle the unyielding scourge, which has cost an estimated $1 trillion in premature deaths, health care costs, and lost wages since 2001.

Dr. Leana Wen, an emergency physician by training and the health commissioner for hard-hit Baltimore, said Capitol Hill has to help communities at risk of becoming overwhelmed.

“We haven’t seen the peak of the epidemic. We are seeing the numbers climb year after year,” she said.

Provisional data from the Centers for Disease Control and Prevention suggest that almost 45,000 Americans died from opioid overdoses in the 12-month period ending July 2017, up from about 38,000 in the previous cycle. (Those data are likely to change, since many death certificates have not yet been reported to the CDC.)

“It’s not going to get any better unless we take dramatic action,” Dr. Wen said.

And the time for most meaningful change could be dwindling. Advocates say what they need most is money, which would most likely come through the government spending bill that’s due March 23. But they aren’t holding their breath.

Show me the money

The federal budget deal, which was signed into law in early February, promised $6 billion over 2 years for initiatives to fight opioid abuse. Congress is still figuring out how to divvy up those funds. The blueprint is expected to be included in the spending bill this week.

In February, a bipartisan group of senators introduced a bill that would add another $1 billion in funding to support expanded treatment and also limit clinicians to prescribing no more than 3 days’ worth of opioids at a time.

That legislation is likely to have wide support in the Senate, but its path through the House is less certain.

This cash infusion is still not going to be enough, predicted Daniel Raymond, policy director for the Harm Reduction Coalition, a national organization that works on overdose prevention.

“It’s not clear whether there’s a real appetite to go as far as we need to see Congress go,” he said. “To have a fighting chance, we need a long-term commitment of at least $10 billion per year.” Academic experts said that assessment sounded on target.

The figure is more than 3 times what’s allocated in the budget and 10 times what even the new Senate bill would provide, and far beyond the spending levels put forth by any previous packages to fight the opioid epidemic.

The difficulty in getting funding – and a key reason why the bipartisan Senate bill might stall in the House – in part goes to the heart of Republicans’ philosophy about budgeting.

The GOP, which controls both chambers of Congress, has “always been very focused on pay-fors,” said a Republican aide to the House Energy and Commerce Committee, explaining that new funding is generally expected to be accompanied by cuts in current expenditures so that overall government spending doesn’t rise. And that could limit how much money lawmakers are ultimately willing to commit to fight opioid abuse.

Some observers worry this notion is pound-foolish.

“We have an enormous set of costs ahead of us if we don’t invest now,” said Dr. Traci Green, an associate professor of emergency medicine and community health science at Boston University, who has extensively researched the epidemic.

Ahead in Congress

Meanwhile, the House could take up its version of a separate Senate-passed proposal designed to, in certain cases, make more prominent any opioid history in a patient’s medical record. The idea is to prevent doctors from prescribing opioids to at-risk patients.

In addition, the House’s Energy and Commerce Committee in late February held a hearing focused on “enforcement” – discussing, for instance, giving the federal Drug Enforcement Administration more power in drug trafficking, and whether to treat fentanyl, a particularly potent synthetic opioid, as a controlled substance. The hearings March 21-22 will tackle a slew of public health–oriented bills, such as making sure overdose patients in the emergency room get appropriate medication and treatment upon discharge, or expanding access to buprenorphine, which is used to treat addiction.

And the House Ways and Means Committee, which has jurisdiction over Medicare – the federal insurance plan for seniors and disabled people – is working to develop strategies that limit access to opioids and make treatment more available.

These are some promising ideas, Mr. Raymond said, but it’s still “playing catch-up. … The big gap is the money, and the broader vision.”

This flurry of activity comes after Congress in 2016 passed two laws directly dealing with addiction and substance abuse disorders, the Comprehensive Addiction and Recovery Act and the 21st Century Cures Act. CARA promised $181 million – although it didn’t appropriate those dollars – while the Cures Act provided $1 billion over 2 years.

It’s playing out against the backdrop of steady policy tensions.

The Trump administration, which in October declared the opioid epidemic a public health crisis, has repeatedly pushed a more punitive approach, such as harsher sentences for drug trafficking, including the death penalty, and establishing mandatory minimum sentences. That emphasis, experts said, detracts from other parts of the plan that might highlight, say, addiction treatment.

Instead, those experts emphasized treatment and prevention as well as “harm reduction” ideas such as providing more overdose-antidote medication and funding programs like syringe exchanges.

They say focusing on punishment has been ineffective in the past and neglects the heart of the issue.

Certainly, curbing the flow of illegal drugs is important, Dr. Wen said. But it’s insufficient by itself. And the size of the problem means lawmakers need to provide quicker, more direct aid – not just proposals that tinker “around the edges.”

“We would never refuse any funding, because we need it desperately,” she said. “But ask us what we need.”

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

The nation’s opioid epidemic has been called today’s version of the 1980s AIDS crisis.

In a New Hampshire speech on March 19, President Donald Trump pushed for a tougher federal response, emphasizing a tough-on-crime approach for drug dealers and more funding for treatment. And Congress is upping the ante, via a series of hearings – including one scheduled to last March 21-22 – to study legislation that might tackle the unyielding scourge, which has cost an estimated $1 trillion in premature deaths, health care costs, and lost wages since 2001.

Dr. Leana Wen, an emergency physician by training and the health commissioner for hard-hit Baltimore, said Capitol Hill has to help communities at risk of becoming overwhelmed.

“We haven’t seen the peak of the epidemic. We are seeing the numbers climb year after year,” she said.

Provisional data from the Centers for Disease Control and Prevention suggest that almost 45,000 Americans died from opioid overdoses in the 12-month period ending July 2017, up from about 38,000 in the previous cycle. (Those data are likely to change, since many death certificates have not yet been reported to the CDC.)

“It’s not going to get any better unless we take dramatic action,” Dr. Wen said.

And the time for most meaningful change could be dwindling. Advocates say what they need most is money, which would most likely come through the government spending bill that’s due March 23. But they aren’t holding their breath.

Show me the money

The federal budget deal, which was signed into law in early February, promised $6 billion over 2 years for initiatives to fight opioid abuse. Congress is still figuring out how to divvy up those funds. The blueprint is expected to be included in the spending bill this week.

In February, a bipartisan group of senators introduced a bill that would add another $1 billion in funding to support expanded treatment and also limit clinicians to prescribing no more than 3 days’ worth of opioids at a time.

That legislation is likely to have wide support in the Senate, but its path through the House is less certain.

This cash infusion is still not going to be enough, predicted Daniel Raymond, policy director for the Harm Reduction Coalition, a national organization that works on overdose prevention.

“It’s not clear whether there’s a real appetite to go as far as we need to see Congress go,” he said. “To have a fighting chance, we need a long-term commitment of at least $10 billion per year.” Academic experts said that assessment sounded on target.

The figure is more than 3 times what’s allocated in the budget and 10 times what even the new Senate bill would provide, and far beyond the spending levels put forth by any previous packages to fight the opioid epidemic.

The difficulty in getting funding – and a key reason why the bipartisan Senate bill might stall in the House – in part goes to the heart of Republicans’ philosophy about budgeting.

The GOP, which controls both chambers of Congress, has “always been very focused on pay-fors,” said a Republican aide to the House Energy and Commerce Committee, explaining that new funding is generally expected to be accompanied by cuts in current expenditures so that overall government spending doesn’t rise. And that could limit how much money lawmakers are ultimately willing to commit to fight opioid abuse.

Some observers worry this notion is pound-foolish.

“We have an enormous set of costs ahead of us if we don’t invest now,” said Dr. Traci Green, an associate professor of emergency medicine and community health science at Boston University, who has extensively researched the epidemic.

Ahead in Congress

Meanwhile, the House could take up its version of a separate Senate-passed proposal designed to, in certain cases, make more prominent any opioid history in a patient’s medical record. The idea is to prevent doctors from prescribing opioids to at-risk patients.

In addition, the House’s Energy and Commerce Committee in late February held a hearing focused on “enforcement” – discussing, for instance, giving the federal Drug Enforcement Administration more power in drug trafficking, and whether to treat fentanyl, a particularly potent synthetic opioid, as a controlled substance. The hearings March 21-22 will tackle a slew of public health–oriented bills, such as making sure overdose patients in the emergency room get appropriate medication and treatment upon discharge, or expanding access to buprenorphine, which is used to treat addiction.

And the House Ways and Means Committee, which has jurisdiction over Medicare – the federal insurance plan for seniors and disabled people – is working to develop strategies that limit access to opioids and make treatment more available.

These are some promising ideas, Mr. Raymond said, but it’s still “playing catch-up. … The big gap is the money, and the broader vision.”

This flurry of activity comes after Congress in 2016 passed two laws directly dealing with addiction and substance abuse disorders, the Comprehensive Addiction and Recovery Act and the 21st Century Cures Act. CARA promised $181 million – although it didn’t appropriate those dollars – while the Cures Act provided $1 billion over 2 years.

It’s playing out against the backdrop of steady policy tensions.

The Trump administration, which in October declared the opioid epidemic a public health crisis, has repeatedly pushed a more punitive approach, such as harsher sentences for drug trafficking, including the death penalty, and establishing mandatory minimum sentences. That emphasis, experts said, detracts from other parts of the plan that might highlight, say, addiction treatment.

Instead, those experts emphasized treatment and prevention as well as “harm reduction” ideas such as providing more overdose-antidote medication and funding programs like syringe exchanges.

They say focusing on punishment has been ineffective in the past and neglects the heart of the issue.

Certainly, curbing the flow of illegal drugs is important, Dr. Wen said. But it’s insufficient by itself. And the size of the problem means lawmakers need to provide quicker, more direct aid – not just proposals that tinker “around the edges.”

“We would never refuse any funding, because we need it desperately,” she said. “But ask us what we need.”

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

Higher dietary intake of red meat and processed meats such as salami may increase the risk of nonalcoholic fatty liver disease and insulin resistance, new research suggests.

In a cross-sectional study, published in the March 20 edition of the Journal of Hepatology, researchers used food-frequency questionnaires to examine red and processed meat consumption in 789 adults aged 40-70 years, including information on cooking methods.

copyright Fuse/Thinkstock

They found that those who reported a total meat intake above the median had a significant 49% higher odds of nonalcoholic fatty liver disease (NAFLD) (95% confidence interval, 1.05-2.13; P = .028) and 63% greater odds of insulin resistance (95% CI, 1.12-2.37, P = .011), even after adjustment for potential confounders such as body mass index, physical activity, smoking, alcohol, and saturated fat and cholesterol intake.

Those whose intake of red and/or processed meat was above the median had a 47% greater odds of NAFLD (P = .031), and a 55% greater odds of insulin resistance (P = .020).

Even when the analysis was limited to nondiabetic participants, the study still showed a significant relationship between higher intake of red and processed meat, and insulin resistance (J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015).

“It can be claimed that the harmful association with meat may, at least partially, be related to a generally less healthy diet or lifestyle characterizing people who eat more red or processed meat, rather than a causal effect of meat,” wrote Shira Zelber-Sagi, PhD, of the department of gastroenterology at Tel Aviv Medical Center, and coauthors. “However, in the current study we meticulously adjusted the association with meat for other nutritional and lifestyle parameters to minimize confounding as much as possible.”

There was also a significant association between unhealthy cooking methods such as frying, broiling, and grilling – which are known to increase the quantity of heterocyclic amines (HCA) in the meat – and insulin resistance.

Individuals who ate one or more portions of meat cooked by these methods showed a higher incidence of insulin resistance compared with those who ate fewer than one portion per week (36.00% vs. 22.20%, P = .004). Researchers also used the food-frequency questionnaires to calculate the quantity of participants’ HCA intake, and found a significantly higher odds of insulin resistance in individuals whose HCA intake was above the median.

Even among the 305 individuals with NAFLD, higher total meat intake, and higher red and processed meat intake, the prevalence of insulin resistance was higher.

In this group, high HCA intake and high consumption of meat cooked by the unhealthy methods were associated with a fourfold higher odds of insulin resistance.

“Potential mechanisms for NAFLD may be related to the formation of reactive species during HCA metabolism, which can cause oxidation of lipids, proteins, and nucleic acids, resulting in oxidative stress, cell damage, and loss of biological function,” the authors wrote. “HCAs were also demonstrated to be bioactive in adipocytes in vitro, leading to increased expression of genes related to inflammation, diabetes and cancer risk.”

The authors noted that their findings supported the recommendations in dietary guidelines for cardiometabolic health, which suggest no more than one to two 100-g servings per week of red meat, and no more than one 50-g serving per week of processed meats.

“Although the specific effect of different types of meat and their quantities in NAFLD requires further research, these recommendations may be helpful in the treatment of patients with NAFLD at least in terms of CVD and diabetes prevention, and maybe for NAFLD prevention by reducing insulin resistance.”

The Israeli Ministry of Health supported the study. No conflicts of interest were declared.

SOURCE: Zelber-Sagi S et al. J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015.

Higher dietary intake of red meat and processed meats such as salami may increase the risk of nonalcoholic fatty liver disease and insulin resistance, new research suggests.

In a cross-sectional study, published in the March 20 edition of the Journal of Hepatology, researchers used food-frequency questionnaires to examine red and processed meat consumption in 789 adults aged 40-70 years, including information on cooking methods.

copyright Fuse/Thinkstock

They found that those who reported a total meat intake above the median had a significant 49% higher odds of nonalcoholic fatty liver disease (NAFLD) (95% confidence interval, 1.05-2.13; P = .028) and 63% greater odds of insulin resistance (95% CI, 1.12-2.37, P = .011), even after adjustment for potential confounders such as body mass index, physical activity, smoking, alcohol, and saturated fat and cholesterol intake.

Those whose intake of red and/or processed meat was above the median had a 47% greater odds of NAFLD (P = .031), and a 55% greater odds of insulin resistance (P = .020).

Even when the analysis was limited to nondiabetic participants, the study still showed a significant relationship between higher intake of red and processed meat, and insulin resistance (J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015).

“It can be claimed that the harmful association with meat may, at least partially, be related to a generally less healthy diet or lifestyle characterizing people who eat more red or processed meat, rather than a causal effect of meat,” wrote Shira Zelber-Sagi, PhD, of the department of gastroenterology at Tel Aviv Medical Center, and coauthors. “However, in the current study we meticulously adjusted the association with meat for other nutritional and lifestyle parameters to minimize confounding as much as possible.”

There was also a significant association between unhealthy cooking methods such as frying, broiling, and grilling – which are known to increase the quantity of heterocyclic amines (HCA) in the meat – and insulin resistance.

Individuals who ate one or more portions of meat cooked by these methods showed a higher incidence of insulin resistance compared with those who ate fewer than one portion per week (36.00% vs. 22.20%, P = .004). Researchers also used the food-frequency questionnaires to calculate the quantity of participants’ HCA intake, and found a significantly higher odds of insulin resistance in individuals whose HCA intake was above the median.

Even among the 305 individuals with NAFLD, higher total meat intake, and higher red and processed meat intake, the prevalence of insulin resistance was higher.

In this group, high HCA intake and high consumption of meat cooked by the unhealthy methods were associated with a fourfold higher odds of insulin resistance.

“Potential mechanisms for NAFLD may be related to the formation of reactive species during HCA metabolism, which can cause oxidation of lipids, proteins, and nucleic acids, resulting in oxidative stress, cell damage, and loss of biological function,” the authors wrote. “HCAs were also demonstrated to be bioactive in adipocytes in vitro, leading to increased expression of genes related to inflammation, diabetes and cancer risk.”

The authors noted that their findings supported the recommendations in dietary guidelines for cardiometabolic health, which suggest no more than one to two 100-g servings per week of red meat, and no more than one 50-g serving per week of processed meats.

“Although the specific effect of different types of meat and their quantities in NAFLD requires further research, these recommendations may be helpful in the treatment of patients with NAFLD at least in terms of CVD and diabetes prevention, and maybe for NAFLD prevention by reducing insulin resistance.”

The Israeli Ministry of Health supported the study. No conflicts of interest were declared.

SOURCE: Zelber-Sagi S et al. J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015.

Higher dietary intake of red meat and processed meats such as salami may increase the risk of nonalcoholic fatty liver disease and insulin resistance, new research suggests.

In a cross-sectional study, published in the March 20 edition of the Journal of Hepatology, researchers used food-frequency questionnaires to examine red and processed meat consumption in 789 adults aged 40-70 years, including information on cooking methods.

copyright Fuse/Thinkstock

They found that those who reported a total meat intake above the median had a significant 49% higher odds of nonalcoholic fatty liver disease (NAFLD) (95% confidence interval, 1.05-2.13; P = .028) and 63% greater odds of insulin resistance (95% CI, 1.12-2.37, P = .011), even after adjustment for potential confounders such as body mass index, physical activity, smoking, alcohol, and saturated fat and cholesterol intake.

Those whose intake of red and/or processed meat was above the median had a 47% greater odds of NAFLD (P = .031), and a 55% greater odds of insulin resistance (P = .020).

Even when the analysis was limited to nondiabetic participants, the study still showed a significant relationship between higher intake of red and processed meat, and insulin resistance (J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015).

“It can be claimed that the harmful association with meat may, at least partially, be related to a generally less healthy diet or lifestyle characterizing people who eat more red or processed meat, rather than a causal effect of meat,” wrote Shira Zelber-Sagi, PhD, of the department of gastroenterology at Tel Aviv Medical Center, and coauthors. “However, in the current study we meticulously adjusted the association with meat for other nutritional and lifestyle parameters to minimize confounding as much as possible.”

There was also a significant association between unhealthy cooking methods such as frying, broiling, and grilling – which are known to increase the quantity of heterocyclic amines (HCA) in the meat – and insulin resistance.

Individuals who ate one or more portions of meat cooked by these methods showed a higher incidence of insulin resistance compared with those who ate fewer than one portion per week (36.00% vs. 22.20%, P = .004). Researchers also used the food-frequency questionnaires to calculate the quantity of participants’ HCA intake, and found a significantly higher odds of insulin resistance in individuals whose HCA intake was above the median.

Even among the 305 individuals with NAFLD, higher total meat intake, and higher red and processed meat intake, the prevalence of insulin resistance was higher.

In this group, high HCA intake and high consumption of meat cooked by the unhealthy methods were associated with a fourfold higher odds of insulin resistance.

“Potential mechanisms for NAFLD may be related to the formation of reactive species during HCA metabolism, which can cause oxidation of lipids, proteins, and nucleic acids, resulting in oxidative stress, cell damage, and loss of biological function,” the authors wrote. “HCAs were also demonstrated to be bioactive in adipocytes in vitro, leading to increased expression of genes related to inflammation, diabetes and cancer risk.”

The authors noted that their findings supported the recommendations in dietary guidelines for cardiometabolic health, which suggest no more than one to two 100-g servings per week of red meat, and no more than one 50-g serving per week of processed meats.

“Although the specific effect of different types of meat and their quantities in NAFLD requires further research, these recommendations may be helpful in the treatment of patients with NAFLD at least in terms of CVD and diabetes prevention, and maybe for NAFLD prevention by reducing insulin resistance.”

The Israeli Ministry of Health supported the study. No conflicts of interest were declared.

SOURCE: Zelber-Sagi S et al. J Hepatol. 2018 Mar 20. doi: 10.1016/j.jhep.2018.01.015.

The Food and Drug Administration has approved Hizentra as the first subcutaneously administered human immunoglobulin maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP), according to a statement from its manufacturer, CSL Behring.

Immune globulin subcutaneous (human) 20% liquid (Hizentra) was approved at doses of 0.2 and 0.4 g/kg per week because of the strength of the phase 3 PATH (Polyneuropathy and Treatment with Hizentra) clinical trial and the PATH extension study, which is still ongoing. PATH is the largest and longest running randomized study of patients with CIDP. The clinical trial studied the safety, efficacy, and tolerability of the two different doses of the subcutaneous immunoglobulin in 172 patients.

The European Commission also recently granted marketing authorization for Hizentra based on the information from the PATH trial.

Hizentra was initially approved in the United States in 2010 for primary immunodeficiency in patients aged 2 years and older.

Since Hizentra is a self-administered drug, it is important for physicians to teach their patients how to properly inject this treatment without hitting a blood vessel. Apart from issues related to self-administration, the risk of thrombosis is also present, which is not uncommon for immune globulin products.

[email protected]

The Food and Drug Administration has approved Hizentra as the first subcutaneously administered human immunoglobulin maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP), according to a statement from its manufacturer, CSL Behring.

Immune globulin subcutaneous (human) 20% liquid (Hizentra) was approved at doses of 0.2 and 0.4 g/kg per week because of the strength of the phase 3 PATH (Polyneuropathy and Treatment with Hizentra) clinical trial and the PATH extension study, which is still ongoing. PATH is the largest and longest running randomized study of patients with CIDP. The clinical trial studied the safety, efficacy, and tolerability of the two different doses of the subcutaneous immunoglobulin in 172 patients.

The European Commission also recently granted marketing authorization for Hizentra based on the information from the PATH trial.

Hizentra was initially approved in the United States in 2010 for primary immunodeficiency in patients aged 2 years and older.

Since Hizentra is a self-administered drug, it is important for physicians to teach their patients how to properly inject this treatment without hitting a blood vessel. Apart from issues related to self-administration, the risk of thrombosis is also present, which is not uncommon for immune globulin products.

[email protected]

The Food and Drug Administration has approved Hizentra as the first subcutaneously administered human immunoglobulin maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP), according to a statement from its manufacturer, CSL Behring.

Immune globulin subcutaneous (human) 20% liquid (Hizentra) was approved at doses of 0.2 and 0.4 g/kg per week because of the strength of the phase 3 PATH (Polyneuropathy and Treatment with Hizentra) clinical trial and the PATH extension study, which is still ongoing. PATH is the largest and longest running randomized study of patients with CIDP. The clinical trial studied the safety, efficacy, and tolerability of the two different doses of the subcutaneous immunoglobulin in 172 patients.

The European Commission also recently granted marketing authorization for Hizentra based on the information from the PATH trial.

Hizentra was initially approved in the United States in 2010 for primary immunodeficiency in patients aged 2 years and older.

Since Hizentra is a self-administered drug, it is important for physicians to teach their patients how to properly inject this treatment without hitting a blood vessel. Apart from issues related to self-administration, the risk of thrombosis is also present, which is not uncommon for immune globulin products.

[email protected]

ORLANDO – A 2014 Food and Drug Administration Safety Communication warning about the risk of disseminating occult cancerous tissue when using power morcellation led to a sharp decline in its use among physicians in a large health care system, a survey and records review showed.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Taylor GB et al. SGS 2018, Oral Poster 19.

ORLANDO – A 2014 Food and Drug Administration Safety Communication warning about the risk of disseminating occult cancerous tissue when using power morcellation led to a sharp decline in its use among physicians in a large health care system, a survey and records review showed.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Taylor GB et al. SGS 2018, Oral Poster 19.

ORLANDO – A 2014 Food and Drug Administration Safety Communication warning about the risk of disseminating occult cancerous tissue when using power morcellation led to a sharp decline in its use among physicians in a large health care system, a survey and records review showed.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Taylor GB et al. SGS 2018, Oral Poster 19.

Every day, hospitalists devote time and energy to the best practices that can limit the spread of infection and the development of antibiotic resistance. Infection Prevention (IP) and Antimicrobial Stewardship (ASP) are two hospital programs that address that same goal.

But there may be a more effective approach possible, according to Jerome A. Leis, MD, MSc, FRCPC, of the Centre for Quality Improvement and Patient Safety at the University of Toronto.

“Despite the high-quality evidence supporting these IP/ASP interventions, our approach to adding these to our current practice sometimes feels like adding scaffolding to a rickety building,” he said. “It supports the underlying structure, but remove the scaffolding without fixing the building, and it may just come tumbling down.” Sometimes the work seems like an uphill battle, he added, as the same problems continue to recur.

That’s because there’s a systemic element to the problems. “Hospitalists know first hand about how the system that we work in makes it difficult to ensure that all the best IP/ASP practices are adhered to all the time,” Dr. Leis said. “Simply reminding staff to remove a urinary catheter in a timely fashion or clean their hands every single time they touch a patient or the environment can only get us so far.” That’s where improvement science comes in.

The relatively new field of improvement science provides a framework for research focused on health care improvement; its goal is to determine which improvement strategies are most effective. Dr. Leis argued that, “when our approach to IP and ASP incorporate principles of improvement science, we are more likely to be successful in achieving sustainable changes in practice.”

Rather than constantly adding extra steps and reminders for hospitalists about patient safety, he said, we need to recognize that there are systemic factors that lead to specific practices. “Our focus should be to use improvement-science methodology to understand these barriers and redesign the processes of care in a way that makes it easier for hospitalists to adhere to the best IP/ASP practices for our patients.”

These structural changes should come from collaboration among content experts in IP/ASP and those with training in improvement science, he said – many IP and ASP programs are already putting this in practice, using improvement science to create safer systems of care.

Reference

Leis J. Advancing infection prevention and antimicrobial stewardship through improvement science. BMJ Qual Saf. 2017 Jun 14. doi: 10.1136/bmjqs-2017-006793.

Every day, hospitalists devote time and energy to the best practices that can limit the spread of infection and the development of antibiotic resistance. Infection Prevention (IP) and Antimicrobial Stewardship (ASP) are two hospital programs that address that same goal.

But there may be a more effective approach possible, according to Jerome A. Leis, MD, MSc, FRCPC, of the Centre for Quality Improvement and Patient Safety at the University of Toronto.

“Despite the high-quality evidence supporting these IP/ASP interventions, our approach to adding these to our current practice sometimes feels like adding scaffolding to a rickety building,” he said. “It supports the underlying structure, but remove the scaffolding without fixing the building, and it may just come tumbling down.” Sometimes the work seems like an uphill battle, he added, as the same problems continue to recur.

That’s because there’s a systemic element to the problems. “Hospitalists know first hand about how the system that we work in makes it difficult to ensure that all the best IP/ASP practices are adhered to all the time,” Dr. Leis said. “Simply reminding staff to remove a urinary catheter in a timely fashion or clean their hands every single time they touch a patient or the environment can only get us so far.” That’s where improvement science comes in.

The relatively new field of improvement science provides a framework for research focused on health care improvement; its goal is to determine which improvement strategies are most effective. Dr. Leis argued that, “when our approach to IP and ASP incorporate principles of improvement science, we are more likely to be successful in achieving sustainable changes in practice.”

Rather than constantly adding extra steps and reminders for hospitalists about patient safety, he said, we need to recognize that there are systemic factors that lead to specific practices. “Our focus should be to use improvement-science methodology to understand these barriers and redesign the processes of care in a way that makes it easier for hospitalists to adhere to the best IP/ASP practices for our patients.”

These structural changes should come from collaboration among content experts in IP/ASP and those with training in improvement science, he said – many IP and ASP programs are already putting this in practice, using improvement science to create safer systems of care.

Reference

Leis J. Advancing infection prevention and antimicrobial stewardship through improvement science. BMJ Qual Saf. 2017 Jun 14. doi: 10.1136/bmjqs-2017-006793.

Every day, hospitalists devote time and energy to the best practices that can limit the spread of infection and the development of antibiotic resistance. Infection Prevention (IP) and Antimicrobial Stewardship (ASP) are two hospital programs that address that same goal.

But there may be a more effective approach possible, according to Jerome A. Leis, MD, MSc, FRCPC, of the Centre for Quality Improvement and Patient Safety at the University of Toronto.

“Despite the high-quality evidence supporting these IP/ASP interventions, our approach to adding these to our current practice sometimes feels like adding scaffolding to a rickety building,” he said. “It supports the underlying structure, but remove the scaffolding without fixing the building, and it may just come tumbling down.” Sometimes the work seems like an uphill battle, he added, as the same problems continue to recur.

That’s because there’s a systemic element to the problems. “Hospitalists know first hand about how the system that we work in makes it difficult to ensure that all the best IP/ASP practices are adhered to all the time,” Dr. Leis said. “Simply reminding staff to remove a urinary catheter in a timely fashion or clean their hands every single time they touch a patient or the environment can only get us so far.” That’s where improvement science comes in.

The relatively new field of improvement science provides a framework for research focused on health care improvement; its goal is to determine which improvement strategies are most effective. Dr. Leis argued that, “when our approach to IP and ASP incorporate principles of improvement science, we are more likely to be successful in achieving sustainable changes in practice.”

Rather than constantly adding extra steps and reminders for hospitalists about patient safety, he said, we need to recognize that there are systemic factors that lead to specific practices. “Our focus should be to use improvement-science methodology to understand these barriers and redesign the processes of care in a way that makes it easier for hospitalists to adhere to the best IP/ASP practices for our patients.”

These structural changes should come from collaboration among content experts in IP/ASP and those with training in improvement science, he said – many IP and ASP programs are already putting this in practice, using improvement science to create safer systems of care.

Reference

Leis J. Advancing infection prevention and antimicrobial stewardship through improvement science. BMJ Qual Saf. 2017 Jun 14. doi: 10.1136/bmjqs-2017-006793.

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

The Diagnosis: Glochid Dermatitis

Biopsy of a nodule on the upper right arm showed chronic granulomatous inflammation and polarizable foreign material consistent with plant cellulose (Figure). A diagnosis of glochid dermatitis was made. The treatment plan included follow-up skin evaluation and punch excision of persistent papules 1 month after the initial presentation. The patient reported the rash began after he fell on a cactus plant while chasing his grandson. He was seen by various clinicians and was given hydrocortisone and clobetasol, which helped with pruritis but did not resolve the rash. His grandson developed a similar rash at the site of contact with the cactus plant. The patient and his grandson did not detect the presence of any cactus spines.

Injuries from cactus glochids most often occur due to accidental falls on cactus plants, but glochids also may be transferred from clothing to other individuals. The thin, hairlike glochids easily detach from the stem of the cactus and can become deeply embedded with virtually no pressure.¹

Glochid implantation from the prickly pear cactus commonly presents as a pruritic papular eruption known as glochid dermatitis. These penetrating injuries can lead to inoculation of Clostridium tetani and Staphylococcus aureus. Additionally, unrecognized and unremoved cactus spines may be highly inflammatory and may cause chronic granulomatous inflammation.²

Initially, acute glochid dermatitis occurs due to mechanical damage caused by the detatched cactus spine and may not resolve for up to 4 months. Granuloma formation has been reported several weeks after exposure and may persist for more than 8 months.³ Although an immune mechanism has been suggested, the literature has indicated that delayed hypersensitivity reactions are a more probable cause of the granulomatous inflammation after glochid exposure.³ Madkan et al⁴ reported that relatively few patients developed granulomas after implantation of glochids in the skin, thus suggesting that granuloma formation is an allergic response.

With regard to the pathogenesis of glochid dermatitis, the initial response to foreign plant matter in the dermis involves a neutrophilic infiltrate, which later is replaced by histiocytes; however, the foreign material remains undegraded in the macrophage cytoplasm.⁵ Activated macrophages secrete cytokines that intensify the inflammatory response, resulting in formation of a granuloma around the foreign body. The granuloma acts as a wall to isolate the foreign matter from the rest of the body.⁵

Regarding treatment of chronic granulomas, Madkan et al⁴ reported a case that showed some improvement with clobetasol ointment; however, clinical lesions resolved only after punch biopsies were performed to confirm the diagnosis of cactus spine granuloma. In a controlled study in rabbits, glochids were successfully removed by first detaching the larger clumps with tweezers then applying glue and gauze to the affected area.⁶ After the glue dried, the gauze was peeled off, resulting in the removal of 95% of the implanted glochids. Overall, removal of embedded spines is difficult because the glochids typically radiate in several directions.⁷ Treatment of foreign body granulomas caused by cactus spines can be achieved by expulsion of plant matter remnants and symptomatic treatment using midpotency topical steroids twice daily.⁴ Uncovering and performing punch biopsies of papules also can result in rapid healing of the lesions. Without manual removal of the glochid, lesions can persist for 2 to 8 months until gradual resolution with possible postinflammatory hyperpigmentation.⁴

Click here to read the supplement

Topics include:

• Common problem of nonadherence to CV medications
• Nonadherence as a contributor to poor CV outcomes
• Improvement of adherence in meeting quality payment program criteria
• Urinalysis as a tool to support adherence
• Benefits of using the KardiAssure™ urinalysis test

Click here to read the supplement

Click here to read the supplement

Topics include:

• Common problem of nonadherence to CV medications
• Nonadherence as a contributor to poor CV outcomes
• Improvement of adherence in meeting quality payment program criteria
• Urinalysis as a tool to support adherence
• Benefits of using the KardiAssure™ urinalysis test

Click here to read the supplement

Click here to read the supplement

Topics include:

• Common problem of nonadherence to CV medications
• Nonadherence as a contributor to poor CV outcomes
• Improvement of adherence in meeting quality payment program criteria
• Urinalysis as a tool to support adherence
• Benefits of using the KardiAssure™ urinalysis test

Click here to read the supplement

Vidyard Video

Release Date: March 20, 2018
Expiration Date: March 19, 2019

Note: This activity is no longer available for credit

Agenda

New targeted agents for PTCL
(Duration: 20 minutes)
Pier Luigi Zinzani, MD, PhD
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy

Recently approved therapies for PTCL in Asia:
What have we learned from the US experience?
(Duration: 18 minutes)
Won Seog Kim, MD, PhD
Samsung Medical Center
Seoul, Republic of Korea

Novel combination therapies:
Where are we now and where are we going?
(Duration: 23 minutes)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the conclusion of this educational activity, the healthcare team will be better able to:

• Discuss the treatment and management of peripheral T-cell lymphoma
• Appraise how U.S. T-cell lymphoma treatment experience can impact practice in Asia
• Summarize the importance of combination therapy in peripheral T-cell lymphoma

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

Peripheral T-cell lymphomas (PTCL) are rare, heterogeneous and aggressive neoplasms that are associated with a poor prognosis. In addition, with current therapies, up to 70% of patients undergo relapse or develop refractory disease. Recent evidence has indicated an increase in the incidence of PTCLs and hence current challenges including pathobiology, clinical management, new drug testing as well as clinical trial accrual, need to be addressed. This activity will provide the healthcare team with the ideal foundation to facilitate progress in PTCL treatment and management.

Won Seog Kim, MD, PhD (Presenter)
Samsung Medical Center
Seoul, Republic of Korea
Disclosure: Consulting fees: Celltrion; Contracted research: Takeda; Kyowa-Kirin; J & J; Merck; Donga; Novartis; Celltrion

Owen A. O’Connor, MD, PhD (Presenter)
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA
Disclosure: Contracted research: Celgene; Merck; Spectrum; Agensys

Pier Luigi Zinzani, MD, PhD (Presenter)
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy
Disclosure: Speakers Bureau: Janssen; Merck; Servier; Gilead; Verastem; BMS; Sandoz; Mundipharma

Permissions

Won Seog Kim presentation

Slide 4: Frequency of T and NK-cell lymphomas in Asia
Park S, Ko YH. Peripheral T cell lymphoma in Asia. Int J Hematol 2014;99:227-239. Reprinted with permission of the Japanese Society of Hematology.

Slide 29: Off-label use: 100mg of pembrolizumab, HK, Singapore, Korea
Republished with permission of the American Society of Hematology, from Kwong YL, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood. 2017;129(17):2437-2442; permission conveyed through Copyright Clearance Center, Inc.

Owen A. O’Connor presentation

Slide 12: Schematic of study design, patient disposition, and thrombocytopenia as a function of schedule & dose
Republished with permission of American Society of Hematology, from Amengual JE…O’Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood 2018;131:397-407; permission conveyed through Copyright Clearance Center, Inc.

Slide 13: Summary of response rates across study population for patients treated with romidepsin and pralatrexate
Same as slide above.

Slide 14: Pharmacokinetic parameters for pralatrexate and romidepsin in the study population
Same as slide above.

Slide 15: PFS and OS as a function of treatment in study population
Same as slide above.

Slide 19: The combination of HoME and HDAC inhibitor synergistically produces apoptosis across panel of T-cell lymphomas: tCTCL H9
Marchi E . . . O’Connor OA.The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma. Br J Haematol 2015; 171:215-226.

Slide 20: Supervised hierarchial clustering based on GEP
Same as slide above.

Slide 27: Panobinostat plus bortezomib in PTCL
Reprinted from Lancet Haematol, Tan D, et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. 2015; 2(8):e326-e333, with permission from Elsevier.

Pier Luigi Zinzani presentation

Slides 4, 11: New agents in T-cell lymphomas (2), Belinostat (2)
O’Connor OA, et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol 2015; 33: 2492-2499. Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Slides 5, 8, 10, 12, 18, 20: Pralatrexate (1), Romidepsin (1), Belinostat (1), Brentuximab vedotin – Anaplastic large cell lymphoma (1), Brentuximab vedotin – CD30+ peripheral T-cell lymphoma (1), Off-label compounds in peripheral T-cell lymphomas
Reprinted from Cancer Treat Rev, volume 60, Broccoli A, Argnani L, Zinzani PL. Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease, pp 120-129, © 2017, with permission from Elsevier.

Slides 6, 7: Pralatrexate (2) and Pralatrexate (3)
O’Connor OA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol, 2011; 29: 1182-1189. Reprinted with permission. © 2011 American Society of Clinical Oncology. All rights reserved.

Slide 9: Romidepsin (2)
Coiffier B, et al. J Clin Oncol 2012; 30: 631-636. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 13, 14: Brentuximab vedotin – Anaplastic large cell lymphoma (2), Brentulximab vedotin — Anaplastic large cell lymphoma (3)
Pro B, et al. J Clin Oncol 2012; 30: 2190-2196. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 16, 17: Brentuximab vedotin – Anaplastic large cell lymphoma (5), Brentuximab vedotin – Anaplastic large cell lymphoma (6)
Broccoli A, et al. Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma. Haematologica 2017; 102: 1931-1935. Obtained from the Haematologica Journal website http://www.haematologica.org

Slide 19: Brentuximab vedotin –CD30+ peripheral T-cell lymphomas (2)
Horwitz SM, et al. Blood 2014; 123: 3095-3100. Permission conveyed through Copyright Clearance Center, Inc.

Slide 21: Gemcitabine in peripheral T-cell lymphomas
Zinzani PL, et al. Ann Oncol 2010; 21: 860-863. European Society of Medical Oncology licensee.

Slide 23: Lenalidomide in T-cell lymphomas (2)
Reprinted from Morschhauser F, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer 2013, with permission from Elsevier.

Slides 24, 25: Bendamustine in T-cell lymphomas (1), Bendamustine in T-cell lymphomas (2)
Damaj G, et al. J Clin Oncol 2012; 31: 104-110. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Vidyard Video

Release Date: March 20, 2018
Expiration Date: March 19, 2019

Note: This activity is no longer available for credit

Agenda

New targeted agents for PTCL
(Duration: 20 minutes)
Pier Luigi Zinzani, MD, PhD
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy

Recently approved therapies for PTCL in Asia:
What have we learned from the US experience?
(Duration: 18 minutes)
Won Seog Kim, MD, PhD
Samsung Medical Center
Seoul, Republic of Korea

Novel combination therapies:
Where are we now and where are we going?
(Duration: 23 minutes)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the conclusion of this educational activity, the healthcare team will be better able to:

• Discuss the treatment and management of peripheral T-cell lymphoma
• Appraise how U.S. T-cell lymphoma treatment experience can impact practice in Asia
• Summarize the importance of combination therapy in peripheral T-cell lymphoma

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

Peripheral T-cell lymphomas (PTCL) are rare, heterogeneous and aggressive neoplasms that are associated with a poor prognosis. In addition, with current therapies, up to 70% of patients undergo relapse or develop refractory disease. Recent evidence has indicated an increase in the incidence of PTCLs and hence current challenges including pathobiology, clinical management, new drug testing as well as clinical trial accrual, need to be addressed. This activity will provide the healthcare team with the ideal foundation to facilitate progress in PTCL treatment and management.

Won Seog Kim, MD, PhD (Presenter)
Samsung Medical Center
Seoul, Republic of Korea
Disclosure: Consulting fees: Celltrion; Contracted research: Takeda; Kyowa-Kirin; J & J; Merck; Donga; Novartis; Celltrion

Owen A. O’Connor, MD, PhD (Presenter)
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA
Disclosure: Contracted research: Celgene; Merck; Spectrum; Agensys

Pier Luigi Zinzani, MD, PhD (Presenter)
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy
Disclosure: Speakers Bureau: Janssen; Merck; Servier; Gilead; Verastem; BMS; Sandoz; Mundipharma

Permissions

Won Seog Kim presentation

Slide 4: Frequency of T and NK-cell lymphomas in Asia
Park S, Ko YH. Peripheral T cell lymphoma in Asia. Int J Hematol 2014;99:227-239. Reprinted with permission of the Japanese Society of Hematology.

Slide 29: Off-label use: 100mg of pembrolizumab, HK, Singapore, Korea
Republished with permission of the American Society of Hematology, from Kwong YL, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood. 2017;129(17):2437-2442; permission conveyed through Copyright Clearance Center, Inc.

Owen A. O’Connor presentation

Slide 12: Schematic of study design, patient disposition, and thrombocytopenia as a function of schedule & dose
Republished with permission of American Society of Hematology, from Amengual JE…O’Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood 2018;131:397-407; permission conveyed through Copyright Clearance Center, Inc.

Slide 13: Summary of response rates across study population for patients treated with romidepsin and pralatrexate
Same as slide above.

Slide 14: Pharmacokinetic parameters for pralatrexate and romidepsin in the study population
Same as slide above.

Slide 15: PFS and OS as a function of treatment in study population
Same as slide above.

Slide 19: The combination of HoME and HDAC inhibitor synergistically produces apoptosis across panel of T-cell lymphomas: tCTCL H9
Marchi E . . . O’Connor OA.The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma. Br J Haematol 2015; 171:215-226.

Slide 20: Supervised hierarchial clustering based on GEP
Same as slide above.

Slide 27: Panobinostat plus bortezomib in PTCL
Reprinted from Lancet Haematol, Tan D, et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. 2015; 2(8):e326-e333, with permission from Elsevier.

Pier Luigi Zinzani presentation

Slides 4, 11: New agents in T-cell lymphomas (2), Belinostat (2)
O’Connor OA, et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol 2015; 33: 2492-2499. Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Slides 5, 8, 10, 12, 18, 20: Pralatrexate (1), Romidepsin (1), Belinostat (1), Brentuximab vedotin – Anaplastic large cell lymphoma (1), Brentuximab vedotin – CD30+ peripheral T-cell lymphoma (1), Off-label compounds in peripheral T-cell lymphomas
Reprinted from Cancer Treat Rev, volume 60, Broccoli A, Argnani L, Zinzani PL. Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease, pp 120-129, © 2017, with permission from Elsevier.

Slides 6, 7: Pralatrexate (2) and Pralatrexate (3)
O’Connor OA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol, 2011; 29: 1182-1189. Reprinted with permission. © 2011 American Society of Clinical Oncology. All rights reserved.

Slide 9: Romidepsin (2)
Coiffier B, et al. J Clin Oncol 2012; 30: 631-636. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 13, 14: Brentuximab vedotin – Anaplastic large cell lymphoma (2), Brentulximab vedotin — Anaplastic large cell lymphoma (3)
Pro B, et al. J Clin Oncol 2012; 30: 2190-2196. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 16, 17: Brentuximab vedotin – Anaplastic large cell lymphoma (5), Brentuximab vedotin – Anaplastic large cell lymphoma (6)
Broccoli A, et al. Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma. Haematologica 2017; 102: 1931-1935. Obtained from the Haematologica Journal website http://www.haematologica.org

Slide 19: Brentuximab vedotin –CD30+ peripheral T-cell lymphomas (2)
Horwitz SM, et al. Blood 2014; 123: 3095-3100. Permission conveyed through Copyright Clearance Center, Inc.

Slide 21: Gemcitabine in peripheral T-cell lymphomas
Zinzani PL, et al. Ann Oncol 2010; 21: 860-863. European Society of Medical Oncology licensee.

Slide 23: Lenalidomide in T-cell lymphomas (2)
Reprinted from Morschhauser F, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer 2013, with permission from Elsevier.

Slides 24, 25: Bendamustine in T-cell lymphomas (1), Bendamustine in T-cell lymphomas (2)
Damaj G, et al. J Clin Oncol 2012; 31: 104-110. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Vidyard Video

Release Date: March 20, 2018
Expiration Date: March 19, 2019

Note: This activity is no longer available for credit

Agenda

New targeted agents for PTCL
(Duration: 20 minutes)
Pier Luigi Zinzani, MD, PhD
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy

Recently approved therapies for PTCL in Asia:
What have we learned from the US experience?
(Duration: 18 minutes)
Won Seog Kim, MD, PhD
Samsung Medical Center
Seoul, Republic of Korea

Novel combination therapies:
Where are we now and where are we going?
(Duration: 23 minutes)
Owen A. O’Connor, MD, PhD
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA

Provided by:

Original activity supported by an educational grant from:

Spectrum Pharmaceuticals

Learning Objectives

At the conclusion of this educational activity, the healthcare team will be better able to:

• Discuss the treatment and management of peripheral T-cell lymphoma
• Appraise how U.S. T-cell lymphoma treatment experience can impact practice in Asia
• Summarize the importance of combination therapy in peripheral T-cell lymphoma

Target Audience

Hematologists, oncologists, and other clinicians and scientists with an interest in T-cell lymphoma

Statement of Need

Peripheral T-cell lymphomas (PTCL) are rare, heterogeneous and aggressive neoplasms that are associated with a poor prognosis. In addition, with current therapies, up to 70% of patients undergo relapse or develop refractory disease. Recent evidence has indicated an increase in the incidence of PTCLs and hence current challenges including pathobiology, clinical management, new drug testing as well as clinical trial accrual, need to be addressed. This activity will provide the healthcare team with the ideal foundation to facilitate progress in PTCL treatment and management.

Won Seog Kim, MD, PhD (Presenter)
Samsung Medical Center
Seoul, Republic of Korea
Disclosure: Consulting fees: Celltrion; Contracted research: Takeda; Kyowa-Kirin; J & J; Merck; Donga; Novartis; Celltrion

Owen A. O’Connor, MD, PhD (Presenter)
Columbia University Medical Center
The New York Presbyterian Hospital
New York, NY USA
Disclosure: Contracted research: Celgene; Merck; Spectrum; Agensys

Pier Luigi Zinzani, MD, PhD (Presenter)
Bologna University
Institute of Hematology “Seragnoli”
Bologna, Italy
Disclosure: Speakers Bureau: Janssen; Merck; Servier; Gilead; Verastem; BMS; Sandoz; Mundipharma

Permissions

Won Seog Kim presentation

Slide 4: Frequency of T and NK-cell lymphomas in Asia
Park S, Ko YH. Peripheral T cell lymphoma in Asia. Int J Hematol 2014;99:227-239. Reprinted with permission of the Japanese Society of Hematology.

Slide 29: Off-label use: 100mg of pembrolizumab, HK, Singapore, Korea
Republished with permission of the American Society of Hematology, from Kwong YL, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood. 2017;129(17):2437-2442; permission conveyed through Copyright Clearance Center, Inc.

Owen A. O’Connor presentation

Slide 12: Schematic of study design, patient disposition, and thrombocytopenia as a function of schedule & dose
Republished with permission of American Society of Hematology, from Amengual JE…O’Connor OA. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood 2018;131:397-407; permission conveyed through Copyright Clearance Center, Inc.

Slide 13: Summary of response rates across study population for patients treated with romidepsin and pralatrexate
Same as slide above.

Slide 14: Pharmacokinetic parameters for pralatrexate and romidepsin in the study population
Same as slide above.

Slide 15: PFS and OS as a function of treatment in study population
Same as slide above.

Slide 19: The combination of HoME and HDAC inhibitor synergistically produces apoptosis across panel of T-cell lymphomas: tCTCL H9
Marchi E . . . O’Connor OA.The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma. Br J Haematol 2015; 171:215-226.

Slide 20: Supervised hierarchial clustering based on GEP
Same as slide above.

Slide 27: Panobinostat plus bortezomib in PTCL
Reprinted from Lancet Haematol, Tan D, et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. 2015; 2(8):e326-e333, with permission from Elsevier.

Pier Luigi Zinzani presentation

Slides 4, 11: New agents in T-cell lymphomas (2), Belinostat (2)
O’Connor OA, et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol 2015; 33: 2492-2499. Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

Slides 5, 8, 10, 12, 18, 20: Pralatrexate (1), Romidepsin (1), Belinostat (1), Brentuximab vedotin – Anaplastic large cell lymphoma (1), Brentuximab vedotin – CD30+ peripheral T-cell lymphoma (1), Off-label compounds in peripheral T-cell lymphomas
Reprinted from Cancer Treat Rev, volume 60, Broccoli A, Argnani L, Zinzani PL. Peripheral T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease, pp 120-129, © 2017, with permission from Elsevier.

Slides 6, 7: Pralatrexate (2) and Pralatrexate (3)
O’Connor OA, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol, 2011; 29: 1182-1189. Reprinted with permission. © 2011 American Society of Clinical Oncology. All rights reserved.

Slide 9: Romidepsin (2)
Coiffier B, et al. J Clin Oncol 2012; 30: 631-636. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 13, 14: Brentuximab vedotin – Anaplastic large cell lymphoma (2), Brentulximab vedotin — Anaplastic large cell lymphoma (3)
Pro B, et al. J Clin Oncol 2012; 30: 2190-2196. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Slides 16, 17: Brentuximab vedotin – Anaplastic large cell lymphoma (5), Brentuximab vedotin – Anaplastic large cell lymphoma (6)
Broccoli A, et al. Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma. Haematologica 2017; 102: 1931-1935. Obtained from the Haematologica Journal website http://www.haematologica.org

Slide 19: Brentuximab vedotin –CD30+ peripheral T-cell lymphomas (2)
Horwitz SM, et al. Blood 2014; 123: 3095-3100. Permission conveyed through Copyright Clearance Center, Inc.

Slide 21: Gemcitabine in peripheral T-cell lymphomas
Zinzani PL, et al. Ann Oncol 2010; 21: 860-863. European Society of Medical Oncology licensee.

Slide 23: Lenalidomide in T-cell lymphomas (2)
Reprinted from Morschhauser F, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer 2013, with permission from Elsevier.

Slides 24, 25: Bendamustine in T-cell lymphomas (1), Bendamustine in T-cell lymphomas (2)
Damaj G, et al. J Clin Oncol 2012; 31: 104-110. Reprinted with permission. © 2012 American Society of Clinical Oncology. All rights reserved.

Disclaimer

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Hemedicus, the supporter, or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Some multiple sclerosis patients who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions seen on MRI yet have undetectable JC virus DNA in their cerebrospinal fluid, a cross-sectional, retrospective study has revealed.

The findings show that for some people with MS, PML diagnosis could be delayed if cerebrospinal fluid (CSF) sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to the authors, led by Martijn T. Wijburg, MD, of the MS Center at VU University Medical Center in Amsterdam.

solitude72/iStockphoto

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab (Tysabri)-associated PML during January 2007 and December 2014.

Patients were required to meet one of the following criteria:

• Definite or probable PML, based a positive PCR and MRI findings suggestive of PML, with or without PML symptoms.

• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), 9 patients (16.1%) had undetectable JCV DNA in CSF and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45 years, and the median natalizumab treatment duration was 43 months. Results showed that patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs. 6.7 mL; P = .008). Logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers (Spearman’s rho, 0.32; P = .03). PML lesion volume was also higher in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

The findings appear to show that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay a diagnosis.

“This can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (e.g., when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” they wrote.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume ... as a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR,” they concluded.

They warned that strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative polymerase chain reaction results, which hampers a formal diagnosis of [PML] and may complicate patient treatment.”

Meticulous clinical and MRI follow-up in combination with repeated CSF JCV PCR testing was warranted in these patients, the researchers advised.

They suggested that complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future,” they added.

The study was supported by the Dutch Foundation for MS Research. Individual authors reported support for the research from the Charcot Foundation, the Hertie Foundation, and the National Institutes of Health. Several of the authors reported receiving consultancy fees from pharmaceutical companies.

SOURCE: Wijburg M et al. JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0094

Some multiple sclerosis patients who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions seen on MRI yet have undetectable JC virus DNA in their cerebrospinal fluid, a cross-sectional, retrospective study has revealed.

The findings show that for some people with MS, PML diagnosis could be delayed if cerebrospinal fluid (CSF) sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to the authors, led by Martijn T. Wijburg, MD, of the MS Center at VU University Medical Center in Amsterdam.

solitude72/iStockphoto

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab (Tysabri)-associated PML during January 2007 and December 2014.

Patients were required to meet one of the following criteria:

• Definite or probable PML, based a positive PCR and MRI findings suggestive of PML, with or without PML symptoms.

• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), 9 patients (16.1%) had undetectable JCV DNA in CSF and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45 years, and the median natalizumab treatment duration was 43 months. Results showed that patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs. 6.7 mL; P = .008). Logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers (Spearman’s rho, 0.32; P = .03). PML lesion volume was also higher in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

The findings appear to show that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay a diagnosis.

“This can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (e.g., when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” they wrote.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume ... as a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR,” they concluded.

They warned that strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative polymerase chain reaction results, which hampers a formal diagnosis of [PML] and may complicate patient treatment.”

Meticulous clinical and MRI follow-up in combination with repeated CSF JCV PCR testing was warranted in these patients, the researchers advised.

They suggested that complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future,” they added.

The study was supported by the Dutch Foundation for MS Research. Individual authors reported support for the research from the Charcot Foundation, the Hertie Foundation, and the National Institutes of Health. Several of the authors reported receiving consultancy fees from pharmaceutical companies.

SOURCE: Wijburg M et al. JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0094

Some multiple sclerosis patients who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions seen on MRI yet have undetectable JC virus DNA in their cerebrospinal fluid, a cross-sectional, retrospective study has revealed.

The findings show that for some people with MS, PML diagnosis could be delayed if cerebrospinal fluid (CSF) sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to the authors, led by Martijn T. Wijburg, MD, of the MS Center at VU University Medical Center in Amsterdam.

solitude72/iStockphoto

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab (Tysabri)-associated PML during January 2007 and December 2014.

Patients were required to meet one of the following criteria:

• Definite or probable PML, based a positive PCR and MRI findings suggestive of PML, with or without PML symptoms.

• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), 9 patients (16.1%) had undetectable JCV DNA in CSF and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45 years, and the median natalizumab treatment duration was 43 months. Results showed that patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs. 6.7 mL; P = .008). Logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers (Spearman’s rho, 0.32; P = .03). PML lesion volume was also higher in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

The findings appear to show that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay a diagnosis.

“This can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (e.g., when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” they wrote.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume ... as a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR,” they concluded.

They warned that strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative polymerase chain reaction results, which hampers a formal diagnosis of [PML] and may complicate patient treatment.”

Meticulous clinical and MRI follow-up in combination with repeated CSF JCV PCR testing was warranted in these patients, the researchers advised.

They suggested that complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future,” they added.

The study was supported by the Dutch Foundation for MS Research. Individual authors reported support for the research from the Charcot Foundation, the Hertie Foundation, and the National Institutes of Health. Several of the authors reported receiving consultancy fees from pharmaceutical companies.

SOURCE: Wijburg M et al. JAMA Neurol. 2018 Mar 12. doi: 10.1001/jamaneurol.2018.0094

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.