Is it time to raise the bar on diabetes blood sugar levels? Sudden cardiac death menaces young diabetes patients. There’s room for improvement in treating psoriatic arthritis. And the FDA chief chastises payers over high drug prices.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is it time to raise the bar on diabetes blood sugar levels? Sudden cardiac death menaces young diabetes patients. There’s room for improvement in treating psoriatic arthritis. And the FDA chief chastises payers over high drug prices.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is it time to raise the bar on diabetes blood sugar levels? Sudden cardiac death menaces young diabetes patients. There’s room for improvement in treating psoriatic arthritis. And the FDA chief chastises payers over high drug prices.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

“We were kind of astounded by this—it’s a very unrecognized phenomenon,” said Richard Leigh, MD, assistant clinical investigator at the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Leigh and his co-researchers had discovered that gadolinium, used in brain scans for stroke patients, sometimes leaks into eyes—literally highlighting abnormalities. The finding could lead to more accurate stroke treatment.

The researchers performed MRI scans on 167 stroke patients on admission to the hospital without administering gadolinium and compared those scans to scans taken using gadolinium 2 hours and 24 hours later.

They found that the gadolinium made some eyes glow brightly, marking the location of brain damage. It appeared that the stroke could compromise the blood-ocular barrier. “It looks like the stroke is influencing the eye, and so the eye is reflective of what is going on in the brain,” said Dr. Leigh.

In about three-fourths of patients, gadolinium leaked into the eyes on 1 of the scans: 66% in the 2-hour scan (typically leaking in the aqueous chamber, in the front of the eye) and 75% in the 24-hour scan (typically in in the vitreous chamber, in the back of the eye).

Older patients, those with hypertension and those with brighter spots on their brain scans (associated with brain aging) were more likely to show gadolinium in the vitreous chamber at 24 hours. In a minority of patients, both eye chambers showed gadolinium at 2 hours. In those patients, stroke tended to affect a larger portion of the brain and cause more damage to the blood-brain barrier than did strokes in patients with a slower pattern of gadolinium leakage or no leakage. The researchers observed the phenomenon in both untreated patients and in those who received tPA.

The findings raise the possibility that clinicians could administer a substance to patients that would collect in the eye, like gadolinium, and quickly yield information about the stroke without the need for an MRI, the researchers say. “It’s much easier for us to look inside somebody’s eye than to look into somebody’s brain,” Dr. Leigh said. “So if the eye truly is a window to the brain, we can use one to learn about the other.”

“We were kind of astounded by this—it’s a very unrecognized phenomenon,” said Richard Leigh, MD, assistant clinical investigator at the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Leigh and his co-researchers had discovered that gadolinium, used in brain scans for stroke patients, sometimes leaks into eyes—literally highlighting abnormalities. The finding could lead to more accurate stroke treatment.

The researchers performed MRI scans on 167 stroke patients on admission to the hospital without administering gadolinium and compared those scans to scans taken using gadolinium 2 hours and 24 hours later.

They found that the gadolinium made some eyes glow brightly, marking the location of brain damage. It appeared that the stroke could compromise the blood-ocular barrier. “It looks like the stroke is influencing the eye, and so the eye is reflective of what is going on in the brain,” said Dr. Leigh.

In about three-fourths of patients, gadolinium leaked into the eyes on 1 of the scans: 66% in the 2-hour scan (typically leaking in the aqueous chamber, in the front of the eye) and 75% in the 24-hour scan (typically in in the vitreous chamber, in the back of the eye).

Older patients, those with hypertension and those with brighter spots on their brain scans (associated with brain aging) were more likely to show gadolinium in the vitreous chamber at 24 hours. In a minority of patients, both eye chambers showed gadolinium at 2 hours. In those patients, stroke tended to affect a larger portion of the brain and cause more damage to the blood-brain barrier than did strokes in patients with a slower pattern of gadolinium leakage or no leakage. The researchers observed the phenomenon in both untreated patients and in those who received tPA.

The findings raise the possibility that clinicians could administer a substance to patients that would collect in the eye, like gadolinium, and quickly yield information about the stroke without the need for an MRI, the researchers say. “It’s much easier for us to look inside somebody’s eye than to look into somebody’s brain,” Dr. Leigh said. “So if the eye truly is a window to the brain, we can use one to learn about the other.”

“We were kind of astounded by this—it’s a very unrecognized phenomenon,” said Richard Leigh, MD, assistant clinical investigator at the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Leigh and his co-researchers had discovered that gadolinium, used in brain scans for stroke patients, sometimes leaks into eyes—literally highlighting abnormalities. The finding could lead to more accurate stroke treatment.

The researchers performed MRI scans on 167 stroke patients on admission to the hospital without administering gadolinium and compared those scans to scans taken using gadolinium 2 hours and 24 hours later.

They found that the gadolinium made some eyes glow brightly, marking the location of brain damage. It appeared that the stroke could compromise the blood-ocular barrier. “It looks like the stroke is influencing the eye, and so the eye is reflective of what is going on in the brain,” said Dr. Leigh.

In about three-fourths of patients, gadolinium leaked into the eyes on 1 of the scans: 66% in the 2-hour scan (typically leaking in the aqueous chamber, in the front of the eye) and 75% in the 24-hour scan (typically in in the vitreous chamber, in the back of the eye).

Older patients, those with hypertension and those with brighter spots on their brain scans (associated with brain aging) were more likely to show gadolinium in the vitreous chamber at 24 hours. In a minority of patients, both eye chambers showed gadolinium at 2 hours. In those patients, stroke tended to affect a larger portion of the brain and cause more damage to the blood-brain barrier than did strokes in patients with a slower pattern of gadolinium leakage or no leakage. The researchers observed the phenomenon in both untreated patients and in those who received tPA.

The findings raise the possibility that clinicians could administer a substance to patients that would collect in the eye, like gadolinium, and quickly yield information about the stroke without the need for an MRI, the researchers say. “It’s much easier for us to look inside somebody’s eye than to look into somebody’s brain,” Dr. Leigh said. “So if the eye truly is a window to the brain, we can use one to learn about the other.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

Photo by Esther Dyson

A new study has revealed discrepancies in completion status for trials listed on ClinicalTrials.gov and the EU Clinical Trials Register (EUCTR).

Researchers evaluated nearly 10,500 trials listed on both registries and found that roughly 16% of them were marked as “completed” on one registry and “ongoing” on the other.

Most of these (91%) were listed as “ongoing” on EUCTR but “completed” on ClinicalTrials.gov.

“Trial registries are important public documents,” said Ben Goldacre, of the University of Oxford in the UK.

“Doctors, researchers, and patients rely on the information that trialists post about their clinical trial. Concerningly, we now show that this data is commonly inaccurate.”

Goldacre and his colleague, Jessica Fleminger, also from the University of Oxford, reported these findings in PLOS ONE.

The researchers looked at 10,492 clinical trials that were registered on both ClinicalTrials.gov and EUCTR.

For most of these trials (83.8%, n=8794), completion status was the same on both registries. But there were 1698 trials (16.2%) that were listed as “completed” on one registry and “ongoing” on another.

A majority of the discrepant trials (90.5%, n=1536) were “ongoing” on EUCTR and “complete” on ClinicalTrials.gov.

Overall, 43.1% (4530/10,492) of dual-registered trials were listed as “ongoing” on EUCTR, and 33.9% of these (1536/4530) were listed as “completed” on ClinicalTrials.gov.

Thirty percent (3156/10,492) of dual-registered trials were marked as “ongoing” on ClinicalTrials.gov, and 5.1% (162/3156) of these were marked as “completed” on EUCTR.

Goldacre and Fleminger said it is unclear whether researchers, registry owners, or both are responsible for these errors. Regardless, researchers identifying discrepancies should request clarifications from the trialists, and registry owners should undertake simple cross-checks of data to ensure that completion status is accurate.

Photo by Esther Dyson

A new study has revealed discrepancies in completion status for trials listed on ClinicalTrials.gov and the EU Clinical Trials Register (EUCTR).

Researchers evaluated nearly 10,500 trials listed on both registries and found that roughly 16% of them were marked as “completed” on one registry and “ongoing” on the other.

Most of these (91%) were listed as “ongoing” on EUCTR but “completed” on ClinicalTrials.gov.

“Trial registries are important public documents,” said Ben Goldacre, of the University of Oxford in the UK.

“Doctors, researchers, and patients rely on the information that trialists post about their clinical trial. Concerningly, we now show that this data is commonly inaccurate.”

Goldacre and his colleague, Jessica Fleminger, also from the University of Oxford, reported these findings in PLOS ONE.

The researchers looked at 10,492 clinical trials that were registered on both ClinicalTrials.gov and EUCTR.

For most of these trials (83.8%, n=8794), completion status was the same on both registries. But there were 1698 trials (16.2%) that were listed as “completed” on one registry and “ongoing” on another.

A majority of the discrepant trials (90.5%, n=1536) were “ongoing” on EUCTR and “complete” on ClinicalTrials.gov.

Overall, 43.1% (4530/10,492) of dual-registered trials were listed as “ongoing” on EUCTR, and 33.9% of these (1536/4530) were listed as “completed” on ClinicalTrials.gov.

Thirty percent (3156/10,492) of dual-registered trials were marked as “ongoing” on ClinicalTrials.gov, and 5.1% (162/3156) of these were marked as “completed” on EUCTR.

Goldacre and Fleminger said it is unclear whether researchers, registry owners, or both are responsible for these errors. Regardless, researchers identifying discrepancies should request clarifications from the trialists, and registry owners should undertake simple cross-checks of data to ensure that completion status is accurate.

Photo by Esther Dyson

A new study has revealed discrepancies in completion status for trials listed on ClinicalTrials.gov and the EU Clinical Trials Register (EUCTR).

Researchers evaluated nearly 10,500 trials listed on both registries and found that roughly 16% of them were marked as “completed” on one registry and “ongoing” on the other.

Most of these (91%) were listed as “ongoing” on EUCTR but “completed” on ClinicalTrials.gov.

“Trial registries are important public documents,” said Ben Goldacre, of the University of Oxford in the UK.

“Doctors, researchers, and patients rely on the information that trialists post about their clinical trial. Concerningly, we now show that this data is commonly inaccurate.”

Goldacre and his colleague, Jessica Fleminger, also from the University of Oxford, reported these findings in PLOS ONE.

The researchers looked at 10,492 clinical trials that were registered on both ClinicalTrials.gov and EUCTR.

For most of these trials (83.8%, n=8794), completion status was the same on both registries. But there were 1698 trials (16.2%) that were listed as “completed” on one registry and “ongoing” on another.

A majority of the discrepant trials (90.5%, n=1536) were “ongoing” on EUCTR and “complete” on ClinicalTrials.gov.

Overall, 43.1% (4530/10,492) of dual-registered trials were listed as “ongoing” on EUCTR, and 33.9% of these (1536/4530) were listed as “completed” on ClinicalTrials.gov.

Thirty percent (3156/10,492) of dual-registered trials were marked as “ongoing” on ClinicalTrials.gov, and 5.1% (162/3156) of these were marked as “completed” on EUCTR.

Goldacre and Fleminger said it is unclear whether researchers, registry owners, or both are responsible for these errors. Regardless, researchers identifying discrepancies should request clarifications from the trialists, and registry owners should undertake simple cross-checks of data to ensure that completion status is accurate.

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates

Q) How do you monitor for infection in patients with multiple sclerosis who take disease-modifying therapies?

The answer to this question is “it depends”—on several factors, including current and previous use of disease-modifying therapies (DMTs), concomitant medications, comorbidities, vaccination history, presence of John Cunningham virus (JCV) antibodies (in the case of natalizumab use), and prior or current use of immunosuppressive therapies.

There are many FDA-approved DMTs for multiple sclerosis (MS). Each has a different rate of infection occurring in clinical trials and varying requirements and/or recommendations for safety monitoring. The package inserts for each DMT offer some guidance for clinicians.

Injectable therapies. For two in­terferon therapies—­interferon ß-1b SC and interferon ß-1a—it is recommended to order a complete blood count (CBC), blood chemistry, and liver function tests (LFTs) at baseline, then again at one, three, and six months, and then at ­clinician discretion thereafter.^1,2 For peginterferon ß-1a, ordering a CBC, basic chemistry, and LFTs, at the clinician’s discretion, is advised.³ The package insert for interferon ß-1a IM does not offer specific recommendations for routine safety monitoring.⁴

The package insert for glatiramer acetate offers no recommendations for routine safety monitoring.⁵

In patients for whom two or more DMTs have failed to work, the monoclonal antibody daclizumab may be indicated. Compared to placebo and active comparator, this drug was associated with a higher risk for infection in clinical trials. The most commonly observed types were upper respiratory, urinary tract, and viral infections. There are no recommendations for CBC monitoring with daclizumab, but monthly LFTs are required due to increased risk for hepatic injury.⁶

Oral DMTs. Patients taking fingolimod, teriflunomide, and dimethyl fumarate have increased risk for infection; as a result, there are more safety monitoring recommendations for these medications.^7-9

Prior to starting therapy with fingolimod, baseline CBC, blood chemistries, and varicella antibody testing should be done. ­During therapy, routine CBC testing and LFTs are advised at the clinician’s discretion or if the patient exhibits signs and symptoms of infection (see Table). In clinical trials, fingolimod use was interrupted if the lymphocyte count was sustained at < 200. In rare cases, progressive multifocal leukoencephalopathy (PML) has occurred—so the patient’s age, JCV antibody status, prior use of immunosuppressant therapy, and length of fingolimod treatment should be taken into consideration.⁷

Patients starting teriflunomide should have baseline LFTs and CBC and tuberculosis (TB) testing (either skin or serum), with subsequent monthly LFTs for the first six months on treatment. Some patients may experience neutropenia, thrombocytopenia, and lymphopenia. As a result, patients may have an increased risk for infection. Safety monitoring is at the clinician’s discretion.⁸

For patients initiating dimethyl fumarate, a baseline CBC is recommended, to be repeated every six to 12 months thereafter, and/or as clinically indicated. Since lymphopenia may occur, consider interruption of dimethyl fumarate in patients with lymphocyte counts < 0.5 persisting for more than six months. Rare cases of PML have also occurred; at the first suggestive sign or symptom, dimethyl fumarate should be withheld and appropriate diagnostic testing should be completed.⁹

Natalizumab is an integrin receptor antagonist administered in monthly IV infusions. Patients receiving natalizumab may have increased risk for urinary tract infections, lower respiratory infections, gastroenteritis, vaginitis, and herpes infections. These risks should be monitored at the clinician’s discretion. There have been several cases of PML associated with natalizumab; risk factors include duration of therapy, prior use of immunosuppressants, and presence of JCV antibodies.¹¹

Alemtuzumab is a CD52-directed monoclonal antibody indicated in patients with relapsing forms of MS who have had an inadequate response to at least two DMTs. In clinical trials, subjects had a higher risk for nasopharyngitis, urinary tract infections, upper respiratory infections, sinusitis, herpetic infections, influenza, and bronchitis. Due to the increased risk for infection and secondary autoimmunities, patients are required to have monthly CBC testing, LFTs, and urinalysis for up to 48 months after their last infusion.¹²

Lastly, ocrelizumab is a CD20-directed cytolytic antibody for the treatment of relapsing and progressive forms of MS. In clinical trials, there was a higher incidence of upper and lower respiratory infections, skin infections, and herpes-related infections. Prior to initiating ocrelizumab, hepatitis B virus screening should be completed. There are no specific recommendations for routine monitoring during therapy, although providers should monitor patients clinically for any signs and symptoms of infection.¹³

A word of caution: The common signs and symptoms of infection are listed in the Table. If these symptoms are present in your patient, consider ordering diagnostic testing to evaluate for infection.

Symptoms of PML include progressive unilateral weakness, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. At the first sign or symptom suggestive of PML, the DMT should be discontinued and diagnostic testing performed.

Providers may contact the manufacturer directly for further guidance on DMT surveillance and treatment protocols. —CK

Christen Kutz, PhD, PA-C
Colorado Springs Neurological Associates

TAMPA – The secret to optimal long-term disease control in schizophrenia is to implement the same type of continuous and close management provided to other chronic diseases, like hypertension or inflammatory bowel disease, according to a lecture delivered at the annual meeting of the American College of Psychiatrists.

In the Dean Award Lecture – a talk characterized as “a stroll through the long-term understanding of the treatment of schizophrenia” – Ira D. Glick, MD, said that, although antipsychotics provide the foundation of disease control, patients and families need to understand and respect disease chronicity.

“What I found in a relatively large sample was that the more adherent patients were to their medication, the more likely they were to report adequate satisfaction with their life,” Dr. Glick said. For those who were not adherent, life in general “has been a disaster.”

This finding is not entirely surprising given the power of antipsychotics to change thinking. However, for those engaged in the immediate task of controlling acute symptoms, the importance of chronicity might not be given adequate emphasis. This requires educating patients and their families about the need to embark on lifetime treatment, Dr. Glick said. Like a diagnosis of diabetes, a diagnosis of schizophrenia means constant vigilance for manifestations of disease and appropriate adjustments of therapy to improve long-term outcomes.

Since evaluating the relationship between medication adherence and long-term outcomes in patients with schizophrenia treated at Stanford, the same type of evaluation was conducted with population samples from the Veterans Affairs system and from China. The data “show exactly the same thing,” Dr. Glick said.

It is important to use every available resource in helping patients recognize and deal with schizophrenia chronicity. In addition to engaging families, he believes that organizations such as the National Alliance on Mental Illness or NAMI, are useful sources of support.

Earlier in his career, Dr. Glick participated in a randomized clinical trial of hospitalization for patients with schizophrenia. Recounting that experience, he reported that he was struck by the improvement in outcomes among patients who grasped that schizophrenia must be approached as a chronic disease.

“Once the patient understood what they had, they were much more apt to be adherent and to stay on their medication for their lifetime,” Dr. Glick reported. Although there is evidence that identifying an effective antipsychotic is key to disease control, “you have to talk to the patient, not just throw a medicine at them,” he said. This makes educating patients and families the key step in embarking on indefinite, close disease monitoring.

Control of schizophrenia over time is likely to vary as symptoms wax and wane, but this is true of other chronic disease processes. Diabetes, for example, requires frequent monitoring for and adjustment of blood glucose. Often medications for diabetes must be intensified or switched. The monitoring and management of schizophrenia is analogous.

One strategy for improving control of schizophrenia is to educate patients about this concept. Approaching schizophrenia as a chronic illness like other diseases that require lifetime drugs will help reduce the crises and the adverse effects associated with nonadherence to tight management, Dr. Glick maintained.

Dr. Glick reported financial relationships with Forum Pharmaceuticals, Johnson & Johnson, Neurocrine, Sunovion, and Teva.

TAMPA – The secret to optimal long-term disease control in schizophrenia is to implement the same type of continuous and close management provided to other chronic diseases, like hypertension or inflammatory bowel disease, according to a lecture delivered at the annual meeting of the American College of Psychiatrists.

In the Dean Award Lecture – a talk characterized as “a stroll through the long-term understanding of the treatment of schizophrenia” – Ira D. Glick, MD, said that, although antipsychotics provide the foundation of disease control, patients and families need to understand and respect disease chronicity.

“What I found in a relatively large sample was that the more adherent patients were to their medication, the more likely they were to report adequate satisfaction with their life,” Dr. Glick said. For those who were not adherent, life in general “has been a disaster.”

This finding is not entirely surprising given the power of antipsychotics to change thinking. However, for those engaged in the immediate task of controlling acute symptoms, the importance of chronicity might not be given adequate emphasis. This requires educating patients and their families about the need to embark on lifetime treatment, Dr. Glick said. Like a diagnosis of diabetes, a diagnosis of schizophrenia means constant vigilance for manifestations of disease and appropriate adjustments of therapy to improve long-term outcomes.

Since evaluating the relationship between medication adherence and long-term outcomes in patients with schizophrenia treated at Stanford, the same type of evaluation was conducted with population samples from the Veterans Affairs system and from China. The data “show exactly the same thing,” Dr. Glick said.

It is important to use every available resource in helping patients recognize and deal with schizophrenia chronicity. In addition to engaging families, he believes that organizations such as the National Alliance on Mental Illness or NAMI, are useful sources of support.

Earlier in his career, Dr. Glick participated in a randomized clinical trial of hospitalization for patients with schizophrenia. Recounting that experience, he reported that he was struck by the improvement in outcomes among patients who grasped that schizophrenia must be approached as a chronic disease.

“Once the patient understood what they had, they were much more apt to be adherent and to stay on their medication for their lifetime,” Dr. Glick reported. Although there is evidence that identifying an effective antipsychotic is key to disease control, “you have to talk to the patient, not just throw a medicine at them,” he said. This makes educating patients and families the key step in embarking on indefinite, close disease monitoring.

Control of schizophrenia over time is likely to vary as symptoms wax and wane, but this is true of other chronic disease processes. Diabetes, for example, requires frequent monitoring for and adjustment of blood glucose. Often medications for diabetes must be intensified or switched. The monitoring and management of schizophrenia is analogous.

One strategy for improving control of schizophrenia is to educate patients about this concept. Approaching schizophrenia as a chronic illness like other diseases that require lifetime drugs will help reduce the crises and the adverse effects associated with nonadherence to tight management, Dr. Glick maintained.

Dr. Glick reported financial relationships with Forum Pharmaceuticals, Johnson & Johnson, Neurocrine, Sunovion, and Teva.

TAMPA – The secret to optimal long-term disease control in schizophrenia is to implement the same type of continuous and close management provided to other chronic diseases, like hypertension or inflammatory bowel disease, according to a lecture delivered at the annual meeting of the American College of Psychiatrists.

In the Dean Award Lecture – a talk characterized as “a stroll through the long-term understanding of the treatment of schizophrenia” – Ira D. Glick, MD, said that, although antipsychotics provide the foundation of disease control, patients and families need to understand and respect disease chronicity.

“What I found in a relatively large sample was that the more adherent patients were to their medication, the more likely they were to report adequate satisfaction with their life,” Dr. Glick said. For those who were not adherent, life in general “has been a disaster.”

This finding is not entirely surprising given the power of antipsychotics to change thinking. However, for those engaged in the immediate task of controlling acute symptoms, the importance of chronicity might not be given adequate emphasis. This requires educating patients and their families about the need to embark on lifetime treatment, Dr. Glick said. Like a diagnosis of diabetes, a diagnosis of schizophrenia means constant vigilance for manifestations of disease and appropriate adjustments of therapy to improve long-term outcomes.

Since evaluating the relationship between medication adherence and long-term outcomes in patients with schizophrenia treated at Stanford, the same type of evaluation was conducted with population samples from the Veterans Affairs system and from China. The data “show exactly the same thing,” Dr. Glick said.

It is important to use every available resource in helping patients recognize and deal with schizophrenia chronicity. In addition to engaging families, he believes that organizations such as the National Alliance on Mental Illness or NAMI, are useful sources of support.

Earlier in his career, Dr. Glick participated in a randomized clinical trial of hospitalization for patients with schizophrenia. Recounting that experience, he reported that he was struck by the improvement in outcomes among patients who grasped that schizophrenia must be approached as a chronic disease.

“Once the patient understood what they had, they were much more apt to be adherent and to stay on their medication for their lifetime,” Dr. Glick reported. Although there is evidence that identifying an effective antipsychotic is key to disease control, “you have to talk to the patient, not just throw a medicine at them,” he said. This makes educating patients and families the key step in embarking on indefinite, close disease monitoring.

Control of schizophrenia over time is likely to vary as symptoms wax and wane, but this is true of other chronic disease processes. Diabetes, for example, requires frequent monitoring for and adjustment of blood glucose. Often medications for diabetes must be intensified or switched. The monitoring and management of schizophrenia is analogous.

One strategy for improving control of schizophrenia is to educate patients about this concept. Approaching schizophrenia as a chronic illness like other diseases that require lifetime drugs will help reduce the crises and the adverse effects associated with nonadherence to tight management, Dr. Glick maintained.

Dr. Glick reported financial relationships with Forum Pharmaceuticals, Johnson & Johnson, Neurocrine, Sunovion, and Teva.

A systematic review of 33 studies evaluating nonpharmacological treatments for acne provided what was described as “circumstantial” evidence of efficacy by the authors who conducted the analysis.

The 33 studies evaluated three types of treatments: laser-based and light-based treatments (20), chemical peels (11), and fractional microneedling radiofrequency (2); most were associated with significant reductions in acne lesions in the studies. The evidence for efficacy was “strong” for glycolic acid at concentrations from 10% to 40%, and “moderate” for amino fruit acids at concentrations of 20%-60%, for intense pulsed light (IPL: 400-700 and 870-1,200 nm), and for the diode laser 1450 nm, according to F.M.C. de Vries, MD, of the department of dermatology, Radboud University, Nijmegen, the Netherlands, and coauthors.

However, they added, “although a high rate of statistically significant results was found in most of the studies, indicating efficacy of nonpharmacological therapies, the low methodological quality of the included studies made it difficult to draw clear conclusions.” Most of the studies were limited by factors that included a small number of enrolled participants, short follow-up, and lack of or possibly inadequate blinding in participants and/or clinicians.

Their review of three electronic databases (MEDLINE, Cochrane library, CINAHL) identified the 33 studies evaluating these treatments in 1,404 participants with acne, published between January 2000 and May 2017, which met their inclusion criteria.

Most of the studies on laser- and light-based treatments found a “significant reduction in acne lesions,” including eight that had a control group. However, with two exceptions, “suboptimal methodologic quality of the majority of these studies resulted in limited evidence of efficacy,” they added. The exceptions were two studies that were the basis of their “moderate” rating for IPL and the diode laser: a randomized study of IPL (40-700 and 870-1,200 nm, 100 ms, 20 J/cm², 20 ms, 18 J/cm²), which found that treatment with IPL resulted in a significant reduction in papules, pustules, and comedones, compared with controls; and a randomized controlled study that found that treatment with a diode laser (1,450 nm, 9.5-11.0 J/cm², 29-30 ms) resulted in reductions in inflammatory acne that were statistically significant.

The review provided “circumstantial evidence for nonpharmacological therapies in the treatment of acne vulgaris” and “has created order and structure in resulting outcomes in which a first step towards future research is generated,” the authors concluded. “The large amount of studies performed in the area of acne treatment and the frequent application of these therapies in daily practice indicates a great interest in this topic and the urgent demand for effective nonpharmacological treatment options for acne in addition to the use of conventional therapies,” they added.

The authors had no disclosures. Of the six authors, Dr. de Vries and three other authors are affiliated with HU University of Applied Sciences, Utrecht, the Netherlands, which funded the study.

[email protected]

SOURCE: de Vries FMC et al. J Eur Acad Dermatol Venereol. 2018 Feb 14. doi: 10.1111/jdv.14881.

A systematic review of 33 studies evaluating nonpharmacological treatments for acne provided what was described as “circumstantial” evidence of efficacy by the authors who conducted the analysis.

The 33 studies evaluated three types of treatments: laser-based and light-based treatments (20), chemical peels (11), and fractional microneedling radiofrequency (2); most were associated with significant reductions in acne lesions in the studies. The evidence for efficacy was “strong” for glycolic acid at concentrations from 10% to 40%, and “moderate” for amino fruit acids at concentrations of 20%-60%, for intense pulsed light (IPL: 400-700 and 870-1,200 nm), and for the diode laser 1450 nm, according to F.M.C. de Vries, MD, of the department of dermatology, Radboud University, Nijmegen, the Netherlands, and coauthors.

However, they added, “although a high rate of statistically significant results was found in most of the studies, indicating efficacy of nonpharmacological therapies, the low methodological quality of the included studies made it difficult to draw clear conclusions.” Most of the studies were limited by factors that included a small number of enrolled participants, short follow-up, and lack of or possibly inadequate blinding in participants and/or clinicians.

Their review of three electronic databases (MEDLINE, Cochrane library, CINAHL) identified the 33 studies evaluating these treatments in 1,404 participants with acne, published between January 2000 and May 2017, which met their inclusion criteria.

Most of the studies on laser- and light-based treatments found a “significant reduction in acne lesions,” including eight that had a control group. However, with two exceptions, “suboptimal methodologic quality of the majority of these studies resulted in limited evidence of efficacy,” they added. The exceptions were two studies that were the basis of their “moderate” rating for IPL and the diode laser: a randomized study of IPL (40-700 and 870-1,200 nm, 100 ms, 20 J/cm², 20 ms, 18 J/cm²), which found that treatment with IPL resulted in a significant reduction in papules, pustules, and comedones, compared with controls; and a randomized controlled study that found that treatment with a diode laser (1,450 nm, 9.5-11.0 J/cm², 29-30 ms) resulted in reductions in inflammatory acne that were statistically significant.

The review provided “circumstantial evidence for nonpharmacological therapies in the treatment of acne vulgaris” and “has created order and structure in resulting outcomes in which a first step towards future research is generated,” the authors concluded. “The large amount of studies performed in the area of acne treatment and the frequent application of these therapies in daily practice indicates a great interest in this topic and the urgent demand for effective nonpharmacological treatment options for acne in addition to the use of conventional therapies,” they added.

The authors had no disclosures. Of the six authors, Dr. de Vries and three other authors are affiliated with HU University of Applied Sciences, Utrecht, the Netherlands, which funded the study.

[email protected]

SOURCE: de Vries FMC et al. J Eur Acad Dermatol Venereol. 2018 Feb 14. doi: 10.1111/jdv.14881.

A systematic review of 33 studies evaluating nonpharmacological treatments for acne provided what was described as “circumstantial” evidence of efficacy by the authors who conducted the analysis.

The 33 studies evaluated three types of treatments: laser-based and light-based treatments (20), chemical peels (11), and fractional microneedling radiofrequency (2); most were associated with significant reductions in acne lesions in the studies. The evidence for efficacy was “strong” for glycolic acid at concentrations from 10% to 40%, and “moderate” for amino fruit acids at concentrations of 20%-60%, for intense pulsed light (IPL: 400-700 and 870-1,200 nm), and for the diode laser 1450 nm, according to F.M.C. de Vries, MD, of the department of dermatology, Radboud University, Nijmegen, the Netherlands, and coauthors.

However, they added, “although a high rate of statistically significant results was found in most of the studies, indicating efficacy of nonpharmacological therapies, the low methodological quality of the included studies made it difficult to draw clear conclusions.” Most of the studies were limited by factors that included a small number of enrolled participants, short follow-up, and lack of or possibly inadequate blinding in participants and/or clinicians.

Their review of three electronic databases (MEDLINE, Cochrane library, CINAHL) identified the 33 studies evaluating these treatments in 1,404 participants with acne, published between January 2000 and May 2017, which met their inclusion criteria.

Most of the studies on laser- and light-based treatments found a “significant reduction in acne lesions,” including eight that had a control group. However, with two exceptions, “suboptimal methodologic quality of the majority of these studies resulted in limited evidence of efficacy,” they added. The exceptions were two studies that were the basis of their “moderate” rating for IPL and the diode laser: a randomized study of IPL (40-700 and 870-1,200 nm, 100 ms, 20 J/cm², 20 ms, 18 J/cm²), which found that treatment with IPL resulted in a significant reduction in papules, pustules, and comedones, compared with controls; and a randomized controlled study that found that treatment with a diode laser (1,450 nm, 9.5-11.0 J/cm², 29-30 ms) resulted in reductions in inflammatory acne that were statistically significant.

The review provided “circumstantial evidence for nonpharmacological therapies in the treatment of acne vulgaris” and “has created order and structure in resulting outcomes in which a first step towards future research is generated,” the authors concluded. “The large amount of studies performed in the area of acne treatment and the frequent application of these therapies in daily practice indicates a great interest in this topic and the urgent demand for effective nonpharmacological treatment options for acne in addition to the use of conventional therapies,” they added.

The authors had no disclosures. Of the six authors, Dr. de Vries and three other authors are affiliated with HU University of Applied Sciences, Utrecht, the Netherlands, which funded the study.

[email protected]

SOURCE: de Vries FMC et al. J Eur Acad Dermatol Venereol. 2018 Feb 14. doi: 10.1111/jdv.14881.

ORLANDO – Climate change is not just eroding coastlines and threatening seaside cities and taking lives with increasingly powerful hurricanes, but appears to be contributing to increases in allergy and asthma, an expert told the audience at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Longer pollen seasons, allergens unleashed by felled trees and ripped-up plants, mold growth following floods, and irritants launched into the air by wildfires are some of the concerns that should be alarming physicians and policy makers, said Nelson A. Rosario, MD, PhD, professor of pediatrics at Federal University of Paraná (Brazil).

Thomas R. Collins/Frontline Medical Communications

Gilitukha/Thinkstock

[email protected]

ORLANDO – Climate change is not just eroding coastlines and threatening seaside cities and taking lives with increasingly powerful hurricanes, but appears to be contributing to increases in allergy and asthma, an expert told the audience at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Longer pollen seasons, allergens unleashed by felled trees and ripped-up plants, mold growth following floods, and irritants launched into the air by wildfires are some of the concerns that should be alarming physicians and policy makers, said Nelson A. Rosario, MD, PhD, professor of pediatrics at Federal University of Paraná (Brazil).

Thomas R. Collins/Frontline Medical Communications

Gilitukha/Thinkstock

[email protected]

ORLANDO – Climate change is not just eroding coastlines and threatening seaside cities and taking lives with increasingly powerful hurricanes, but appears to be contributing to increases in allergy and asthma, an expert told the audience at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Longer pollen seasons, allergens unleashed by felled trees and ripped-up plants, mold growth following floods, and irritants launched into the air by wildfires are some of the concerns that should be alarming physicians and policy makers, said Nelson A. Rosario, MD, PhD, professor of pediatrics at Federal University of Paraná (Brazil).

Thomas R. Collins/Frontline Medical Communications

Gilitukha/Thinkstock

[email protected]