Mary Ann Moon

Long-term statin therapy normalized the progression of carotid intima-media thickness in a Dutch study of children with familial hypercholesterolemia, according to a research letter to the editor published online Sept. 9 in JAMA.

Guidelines for treatment of this disorder in children advise the initiation of statin therapy as early as 8 years of age, but long-term efficacy and safety data for treatment initiated in childhood "do not exist," said Dr. D. Meeike Kusters of the department of vascular medicine, Academic Medical Center, Amsterdam, and her associates.

In the late 1990s, the investigators performed a double-blind cohort study in which 214 children aged 8-18 years who were heterozygous for familial hypercholesterolemia were randomly assigned to receive either pravastatin or placebo and were followed for 2 years. They found significant regression of carotid intima-media thickness with active treatment. All of the study participants were then offered treatment and were followed for 10 years, along with their unaffected siblings.

Dr. Kusters and her associates now report the findings from that follow-up of 194 study participants (of whom 163 still use statins) and 83 of their siblings, who now are all aged 18-30 years. Progression of carotid intima-media thickness was similar between the two groups, indicating that statins normalized this progression in affected patients over the long term. Moreover, earlier statin initiation correlated with thinner carotid intima-media thickness a decade later, the researchers said (JAMA 2014:312;1055-7).

No serious adverse events were reported, although three patients discontinued statin therapy because of adverse events. Laboratory safety measures did not differ between patients with familial hypercholesterolemia who took the drugs and their siblings, and there were no differences between the two groups in growth, maturation, or educational attainment. This small study, however, lacked the statistical power to detect rare events.

Despite this beneficial effect, the patients’ LDL-cholesterol levels "did not meet current treatment standards," the investigators wrote, and their carotid intima-media thickness remained greater than that of their unaffected siblings throughout the trial. "More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population," Dr. Kusters and her associates added.

This study was supported by the Dutch Heart Foundation. Dr. Kusters reported no financial conflicts of interest; one of her associates reported receiving lecture fees from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, ISIS, Merck Sharp Dohme, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

pdnews@frontlinemedcom.com

Long-term statin therapy normalized the progression of carotid intima-media thickness in a Dutch study of children with familial hypercholesterolemia, according to a research letter to the editor published online Sept. 9 in JAMA.

Guidelines for treatment of this disorder in children advise the initiation of statin therapy as early as 8 years of age, but long-term efficacy and safety data for treatment initiated in childhood "do not exist," said Dr. D. Meeike Kusters of the department of vascular medicine, Academic Medical Center, Amsterdam, and her associates.

In the late 1990s, the investigators performed a double-blind cohort study in which 214 children aged 8-18 years who were heterozygous for familial hypercholesterolemia were randomly assigned to receive either pravastatin or placebo and were followed for 2 years. They found significant regression of carotid intima-media thickness with active treatment. All of the study participants were then offered treatment and were followed for 10 years, along with their unaffected siblings.

Dr. Kusters and her associates now report the findings from that follow-up of 194 study participants (of whom 163 still use statins) and 83 of their siblings, who now are all aged 18-30 years. Progression of carotid intima-media thickness was similar between the two groups, indicating that statins normalized this progression in affected patients over the long term. Moreover, earlier statin initiation correlated with thinner carotid intima-media thickness a decade later, the researchers said (JAMA 2014:312;1055-7).

No serious adverse events were reported, although three patients discontinued statin therapy because of adverse events. Laboratory safety measures did not differ between patients with familial hypercholesterolemia who took the drugs and their siblings, and there were no differences between the two groups in growth, maturation, or educational attainment. This small study, however, lacked the statistical power to detect rare events.

Despite this beneficial effect, the patients’ LDL-cholesterol levels "did not meet current treatment standards," the investigators wrote, and their carotid intima-media thickness remained greater than that of their unaffected siblings throughout the trial. "More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population," Dr. Kusters and her associates added.

This study was supported by the Dutch Heart Foundation. Dr. Kusters reported no financial conflicts of interest; one of her associates reported receiving lecture fees from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, ISIS, Merck Sharp Dohme, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

pdnews@frontlinemedcom.com

Long-term statin therapy normalized the progression of carotid intima-media thickness in a Dutch study of children with familial hypercholesterolemia, according to a research letter to the editor published online Sept. 9 in JAMA.

Guidelines for treatment of this disorder in children advise the initiation of statin therapy as early as 8 years of age, but long-term efficacy and safety data for treatment initiated in childhood "do not exist," said Dr. D. Meeike Kusters of the department of vascular medicine, Academic Medical Center, Amsterdam, and her associates.

In the late 1990s, the investigators performed a double-blind cohort study in which 214 children aged 8-18 years who were heterozygous for familial hypercholesterolemia were randomly assigned to receive either pravastatin or placebo and were followed for 2 years. They found significant regression of carotid intima-media thickness with active treatment. All of the study participants were then offered treatment and were followed for 10 years, along with their unaffected siblings.

Dr. Kusters and her associates now report the findings from that follow-up of 194 study participants (of whom 163 still use statins) and 83 of their siblings, who now are all aged 18-30 years. Progression of carotid intima-media thickness was similar between the two groups, indicating that statins normalized this progression in affected patients over the long term. Moreover, earlier statin initiation correlated with thinner carotid intima-media thickness a decade later, the researchers said (JAMA 2014:312;1055-7).

No serious adverse events were reported, although three patients discontinued statin therapy because of adverse events. Laboratory safety measures did not differ between patients with familial hypercholesterolemia who took the drugs and their siblings, and there were no differences between the two groups in growth, maturation, or educational attainment. This small study, however, lacked the statistical power to detect rare events.

Despite this beneficial effect, the patients’ LDL-cholesterol levels "did not meet current treatment standards," the investigators wrote, and their carotid intima-media thickness remained greater than that of their unaffected siblings throughout the trial. "More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population," Dr. Kusters and her associates added.

This study was supported by the Dutch Heart Foundation. Dr. Kusters reported no financial conflicts of interest; one of her associates reported receiving lecture fees from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, ISIS, Merck Sharp Dohme, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

pdnews@frontlinemedcom.com

CHICAGO – The “much anticipated” guideline to help primary-care and emergency clinicians improve the management of sickle cell disease includes a consensus treatment protocol for implementing hydroxyurea therapy and more detailed guidance regarding long-term transfusion therapy, according to a summary report published online September 9 in JAMA.

Sickle cell disease (SCD), a life-threatening genetically transmitted disorder affecting 70,000-100,000 Americans, is associated with a wide array of complex acute and chronic complications that require immediate medical attention. But high-quality data on which to base management decisions are sorely lacking, and clinicians get little in the way of guidance from existing recommendations. One result is that “the 2 most widely available disease-modifying therapies, hydroxyurea and long-term transfusions, are underused, and hematopoietic stem cell transplantation, the only curative approach, has been used in only a small proportion of affected individuals,” said Dr. Barbara P. Yawn and her associates on the National Heart, Lung, and Blood Institute expert panel that issued the summary report.

Even this guideline is somewhat rudimentary (Advil) due to the dearth of good data “in virtually every area related to SCD management,” and cannot help but leave “many uncertainties for health professionals caring for individuals with SCD.” But it is hoped that this guideline will furnish a critical foundation for future research will now begin “to facilitate improved and more accessible care for all affected individuals,” said Dr. Yawn, of the department of research and education, Olmsted Medical Center, Rochester MN, and her associates.

The guideline is based on an extensive literature review of more than 13,000 abstracts and articles, which was winnowed to 1,583 original studies regarding SCD. From this, a team of health care professionals in family medicine, internal medicine, pediatric and adult hematology, psychiatry and mental health, transfusion medicine, obstetrics and gynecology, maternal/fetal medicine, and emergency department nursing compiled the guideline as well as the summary, entitled Evidence-Based Management of Sickle Cell Disease: Expert Panel Report 2014 (JAMA 2014 September 9 [doi:10.1001/jama.2014.10517]).

In addition to establishing a protocol for implementing hydroxyurea therapy, the guideline addresses changes in pneumococcal vaccination recommendations for adults and children; annual transcranial Doppler screening coupled with long-term transfusion therapy when necessary, to prevent stroke in children aged 2-16 years; rapid initiation of opioids for severe pain during vasoocclusive crises; analgesics and physical therapy for avascular necrosis; ACE inhibitor treatment for adults with microalbuminuria; referral to specialists for screening and treatment of proliferative retinopathy; echocardiography to assess signs of pulmonary hypertension; and monitoring for iron overload in patients receiving transfusion therapy.

CHICAGO – The “much anticipated” guideline to help primary-care and emergency clinicians improve the management of sickle cell disease includes a consensus treatment protocol for implementing hydroxyurea therapy and more detailed guidance regarding long-term transfusion therapy, according to a summary report published online September 9 in JAMA.

Sickle cell disease (SCD), a life-threatening genetically transmitted disorder affecting 70,000-100,000 Americans, is associated with a wide array of complex acute and chronic complications that require immediate medical attention. But high-quality data on which to base management decisions are sorely lacking, and clinicians get little in the way of guidance from existing recommendations. One result is that “the 2 most widely available disease-modifying therapies, hydroxyurea and long-term transfusions, are underused, and hematopoietic stem cell transplantation, the only curative approach, has been used in only a small proportion of affected individuals,” said Dr. Barbara P. Yawn and her associates on the National Heart, Lung, and Blood Institute expert panel that issued the summary report.

Even this guideline is somewhat rudimentary (Advil) due to the dearth of good data “in virtually every area related to SCD management,” and cannot help but leave “many uncertainties for health professionals caring for individuals with SCD.” But it is hoped that this guideline will furnish a critical foundation for future research will now begin “to facilitate improved and more accessible care for all affected individuals,” said Dr. Yawn, of the department of research and education, Olmsted Medical Center, Rochester MN, and her associates.

The guideline is based on an extensive literature review of more than 13,000 abstracts and articles, which was winnowed to 1,583 original studies regarding SCD. From this, a team of health care professionals in family medicine, internal medicine, pediatric and adult hematology, psychiatry and mental health, transfusion medicine, obstetrics and gynecology, maternal/fetal medicine, and emergency department nursing compiled the guideline as well as the summary, entitled Evidence-Based Management of Sickle Cell Disease: Expert Panel Report 2014 (JAMA 2014 September 9 [doi:10.1001/jama.2014.10517]).

In addition to establishing a protocol for implementing hydroxyurea therapy, the guideline addresses changes in pneumococcal vaccination recommendations for adults and children; annual transcranial Doppler screening coupled with long-term transfusion therapy when necessary, to prevent stroke in children aged 2-16 years; rapid initiation of opioids for severe pain during vasoocclusive crises; analgesics and physical therapy for avascular necrosis; ACE inhibitor treatment for adults with microalbuminuria; referral to specialists for screening and treatment of proliferative retinopathy; echocardiography to assess signs of pulmonary hypertension; and monitoring for iron overload in patients receiving transfusion therapy.

CHICAGO – The “much anticipated” guideline to help primary-care and emergency clinicians improve the management of sickle cell disease includes a consensus treatment protocol for implementing hydroxyurea therapy and more detailed guidance regarding long-term transfusion therapy, according to a summary report published online September 9 in JAMA.

Sickle cell disease (SCD), a life-threatening genetically transmitted disorder affecting 70,000-100,000 Americans, is associated with a wide array of complex acute and chronic complications that require immediate medical attention. But high-quality data on which to base management decisions are sorely lacking, and clinicians get little in the way of guidance from existing recommendations. One result is that “the 2 most widely available disease-modifying therapies, hydroxyurea and long-term transfusions, are underused, and hematopoietic stem cell transplantation, the only curative approach, has been used in only a small proportion of affected individuals,” said Dr. Barbara P. Yawn and her associates on the National Heart, Lung, and Blood Institute expert panel that issued the summary report.

Even this guideline is somewhat rudimentary (Advil) due to the dearth of good data “in virtually every area related to SCD management,” and cannot help but leave “many uncertainties for health professionals caring for individuals with SCD.” But it is hoped that this guideline will furnish a critical foundation for future research will now begin “to facilitate improved and more accessible care for all affected individuals,” said Dr. Yawn, of the department of research and education, Olmsted Medical Center, Rochester MN, and her associates.

The guideline is based on an extensive literature review of more than 13,000 abstracts and articles, which was winnowed to 1,583 original studies regarding SCD. From this, a team of health care professionals in family medicine, internal medicine, pediatric and adult hematology, psychiatry and mental health, transfusion medicine, obstetrics and gynecology, maternal/fetal medicine, and emergency department nursing compiled the guideline as well as the summary, entitled Evidence-Based Management of Sickle Cell Disease: Expert Panel Report 2014 (JAMA 2014 September 9 [doi:10.1001/jama.2014.10517]).

In addition to establishing a protocol for implementing hydroxyurea therapy, the guideline addresses changes in pneumococcal vaccination recommendations for adults and children; annual transcranial Doppler screening coupled with long-term transfusion therapy when necessary, to prevent stroke in children aged 2-16 years; rapid initiation of opioids for severe pain during vasoocclusive crises; analgesics and physical therapy for avascular necrosis; ACE inhibitor treatment for adults with microalbuminuria; referral to specialists for screening and treatment of proliferative retinopathy; echocardiography to assess signs of pulmonary hypertension; and monitoring for iron overload in patients receiving transfusion therapy.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest. 

Before new guidelines advocating universal screening for dyslipidemia at ages 9-11 years and again at ages 17-21 years, 2.8% of normal-weight children in the younger age group and 22% of those in the older age group underwent such screening, according to a report published online Aug. 26 in Circulation: Cardiovascular Quality and Outcomes.

Lipid screening also was low among obese children in these age groups at that time (30.6% and 34.6%, respectively), even though existing recommendations advised such screening in that patient population, said Dr. Karen L. Margolis of the HealthPartners Institute for Education and Research, Minneapolis, and her associates.

©iStock/thinkstockphotos.com

Data are scarce regarding lipid screening practices in the pediatric population, and no studies have yet examined these practices after the release of the recommendation for universal screening in 2011. Dr. Margolis and her associates focused on lipid screening practices during the 3-year period before the recommendations were issued, hoping to establish a benchmark for assessing changes in community practice patterns. They performed a secondary analysis of data collected in a retrospective cohort study of pediatric hypertension and obesity conducted in three large health care delivery systems. Their sample included 301,080 individuals in that cohort study, who were aged 3-19 years.

Overall, 9.8% of the children and adolescents had lipid testing with at least one measurement of total cholesterol. The number who underwent lipid screening increased with increasing patient age, increasing body mass index, and increasing blood pressure. Abnormal levels of total cholesterol were identified in 8.6% of the individuals, abnormal HDL-C levels were identified in 22.5%, abnormal non-HDL-C levels were identified in 12.0%, abnormal LDL-C levels were identified in 8.0%, and abnormal triglycerides were identified in 19%-38%, depending on age and sex, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2014 August 26 [doi:10.1161/Circoutcomes.114.000842]).

"Although abnormal lipid values were more likely to be found in children with elevated BMI, we found some normal-weight children with a low level of HDL-C (12.6%) and a high level of non-HDL-C (6.9%). Thus, targeted screening for [overweight or obese] children would clearly miss some normal-weight children with lipid abnormalities, including [some] with LDL-C levels compatible with familial hypercholesterolemia," they noted. This suggests that more children will be newly identified with the recommended universal lipid screening of children.

This study was funded in part by the National Heart, Lung, and Blood Institute. Dr. Margolis reported no financial conflicts of interest; one of her associates reported ties with Sanofi.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest. 

Before new guidelines advocating universal screening for dyslipidemia at ages 9-11 years and again at ages 17-21 years, 2.8% of normal-weight children in the younger age group and 22% of those in the older age group underwent such screening, according to a report published online Aug. 26 in Circulation: Cardiovascular Quality and Outcomes.

Lipid screening also was low among obese children in these age groups at that time (30.6% and 34.6%, respectively), even though existing recommendations advised such screening in that patient population, said Dr. Karen L. Margolis of the HealthPartners Institute for Education and Research, Minneapolis, and her associates.

©iStock/thinkstockphotos.com

Data are scarce regarding lipid screening practices in the pediatric population, and no studies have yet examined these practices after the release of the recommendation for universal screening in 2011. Dr. Margolis and her associates focused on lipid screening practices during the 3-year period before the recommendations were issued, hoping to establish a benchmark for assessing changes in community practice patterns. They performed a secondary analysis of data collected in a retrospective cohort study of pediatric hypertension and obesity conducted in three large health care delivery systems. Their sample included 301,080 individuals in that cohort study, who were aged 3-19 years.

Overall, 9.8% of the children and adolescents had lipid testing with at least one measurement of total cholesterol. The number who underwent lipid screening increased with increasing patient age, increasing body mass index, and increasing blood pressure. Abnormal levels of total cholesterol were identified in 8.6% of the individuals, abnormal HDL-C levels were identified in 22.5%, abnormal non-HDL-C levels were identified in 12.0%, abnormal LDL-C levels were identified in 8.0%, and abnormal triglycerides were identified in 19%-38%, depending on age and sex, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2014 August 26 [doi:10.1161/Circoutcomes.114.000842]).

"Although abnormal lipid values were more likely to be found in children with elevated BMI, we found some normal-weight children with a low level of HDL-C (12.6%) and a high level of non-HDL-C (6.9%). Thus, targeted screening for [overweight or obese] children would clearly miss some normal-weight children with lipid abnormalities, including [some] with LDL-C levels compatible with familial hypercholesterolemia," they noted. This suggests that more children will be newly identified with the recommended universal lipid screening of children.

This study was funded in part by the National Heart, Lung, and Blood Institute. Dr. Margolis reported no financial conflicts of interest; one of her associates reported ties with Sanofi.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest. 

Before new guidelines advocating universal screening for dyslipidemia at ages 9-11 years and again at ages 17-21 years, 2.8% of normal-weight children in the younger age group and 22% of those in the older age group underwent such screening, according to a report published online Aug. 26 in Circulation: Cardiovascular Quality and Outcomes.

Lipid screening also was low among obese children in these age groups at that time (30.6% and 34.6%, respectively), even though existing recommendations advised such screening in that patient population, said Dr. Karen L. Margolis of the HealthPartners Institute for Education and Research, Minneapolis, and her associates.

©iStock/thinkstockphotos.com

Data are scarce regarding lipid screening practices in the pediatric population, and no studies have yet examined these practices after the release of the recommendation for universal screening in 2011. Dr. Margolis and her associates focused on lipid screening practices during the 3-year period before the recommendations were issued, hoping to establish a benchmark for assessing changes in community practice patterns. They performed a secondary analysis of data collected in a retrospective cohort study of pediatric hypertension and obesity conducted in three large health care delivery systems. Their sample included 301,080 individuals in that cohort study, who were aged 3-19 years.

Overall, 9.8% of the children and adolescents had lipid testing with at least one measurement of total cholesterol. The number who underwent lipid screening increased with increasing patient age, increasing body mass index, and increasing blood pressure. Abnormal levels of total cholesterol were identified in 8.6% of the individuals, abnormal HDL-C levels were identified in 22.5%, abnormal non-HDL-C levels were identified in 12.0%, abnormal LDL-C levels were identified in 8.0%, and abnormal triglycerides were identified in 19%-38%, depending on age and sex, the investigators said (Circ. Cardiovasc. Qual. Outcomes 2014 August 26 [doi:10.1161/Circoutcomes.114.000842]).

"Although abnormal lipid values were more likely to be found in children with elevated BMI, we found some normal-weight children with a low level of HDL-C (12.6%) and a high level of non-HDL-C (6.9%). Thus, targeted screening for [overweight or obese] children would clearly miss some normal-weight children with lipid abnormalities, including [some] with LDL-C levels compatible with familial hypercholesterolemia," they noted. This suggests that more children will be newly identified with the recommended universal lipid screening of children.

This study was funded in part by the National Heart, Lung, and Blood Institute. Dr. Margolis reported no financial conflicts of interest; one of her associates reported ties with Sanofi.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Daily low-dose fish oil capsules reduced seizure frequency by 33.6% in patients with drug-resistant epilepsy in a single-center, randomized, phase II trial.

The report was published Sept. 8 in the Journal of Neurology, Neurosurgery, and Psychiatry.

The magnitude of this effect was similar to that seen in many studies of antiepileptic drugs. Moreover, low-dose fish oil may also yield cardiovascular benefits in this patient population, "a finding of some importance given the recent data that the risk of death due to myocardial infarction is significantly higher in people with epilepsy" than in the general population, said Dr. Christopher M. DeGiorgio of the department of neurology at the University of California, Los Angeles, and his associates.

©Clayton Hansen/iStockphoto

The n-3 fatty acids in fish oil are thought to modify calcium and sodium channels in the brain, reducing membrane excitability in neurons. So far, the results of studies of high-dose fish oil as a treatment for epilepsy have been "promising yet inconclusive." This double-blind, crossover trial compared low-dose and high-dose fish oil and placebo in 25 adults with a mean age of 33 years. At baseline, they had three or more localization-related partial onset or generalized tonic/clonic seizures per month and had failed to respond to at least three antiepileptic drugs.

Each oral gel capsule contained either 216 mg of eicosapentaenoic acid (EPA) and 144 mg of docosahexaenoic acid (DHA), for a total of 360 mg of n-3 fatty acids, or a matching placebo capsule filled with corn oil. All study patients took three fish oil capsules per day (low-dose period), three fish oil capsules twice a day (high-dose period), or placebo capsules (control period) for 10 weeks, with 6-week washout periods between each course, for a total study length of 42 weeks.

The primary endpoint, the average seizure frequency, was 12.18 per month during low-dose fish oil therapy, compared with 17.67 seizures per month for high-dose fish oil and 18.34 seizures per month for placebo. This represents a reduction of 33.6% in seizure frequency with low-dose fish oil. In addition, 5 of 20 patients (25%) showed a 50% reduction in seizures only while taking low-dose fish oil, and 2 of 20 (10%) were free of seizures only while taking low-dose fish oil, Dr. DeGiorgio and his associates said (J. Neurol. Neurosurg. Psychiatry 2014 Sept. 8 [doi:10.1136/jnnp-2014-307749]).

The fish oil capsules proved to be safe, with no serious adverse events occurring during the study. One patient died from autopsy-confirmed sudden death in epilepsy during treatment with high-dose fish oil, but the death was deemed unrelated to fish oil.

It is not yet understood why the low-dose treatment produced better results than the high-dose treatment, the researchers noted.

These findings warrant confirmation in a large, multicenter trial. And it remains to be seen whether this beneficial effect is sustained over time, since the treatment period in this trial was only 10 weeks.

This study was supported by grants from the National Center for Complementary and Alternative Medicine, UCLA’s General Clinical Research Center, and individual donations. Marijo Clark and Pharmavite provided the fish oil and placebo capsules. Dr. DeGiorgio reported no conflicts of interest. An associate disclosed part-time employment with NeuroSigma, which develops devices for epilepsy and other disorders.

Daily low-dose fish oil capsules reduced seizure frequency by 33.6% in patients with drug-resistant epilepsy in a single-center, randomized, phase II trial.

The report was published Sept. 8 in the Journal of Neurology, Neurosurgery, and Psychiatry.

The magnitude of this effect was similar to that seen in many studies of antiepileptic drugs. Moreover, low-dose fish oil may also yield cardiovascular benefits in this patient population, "a finding of some importance given the recent data that the risk of death due to myocardial infarction is significantly higher in people with epilepsy" than in the general population, said Dr. Christopher M. DeGiorgio of the department of neurology at the University of California, Los Angeles, and his associates.

©Clayton Hansen/iStockphoto

The n-3 fatty acids in fish oil are thought to modify calcium and sodium channels in the brain, reducing membrane excitability in neurons. So far, the results of studies of high-dose fish oil as a treatment for epilepsy have been "promising yet inconclusive." This double-blind, crossover trial compared low-dose and high-dose fish oil and placebo in 25 adults with a mean age of 33 years. At baseline, they had three or more localization-related partial onset or generalized tonic/clonic seizures per month and had failed to respond to at least three antiepileptic drugs.

Each oral gel capsule contained either 216 mg of eicosapentaenoic acid (EPA) and 144 mg of docosahexaenoic acid (DHA), for a total of 360 mg of n-3 fatty acids, or a matching placebo capsule filled with corn oil. All study patients took three fish oil capsules per day (low-dose period), three fish oil capsules twice a day (high-dose period), or placebo capsules (control period) for 10 weeks, with 6-week washout periods between each course, for a total study length of 42 weeks.

The primary endpoint, the average seizure frequency, was 12.18 per month during low-dose fish oil therapy, compared with 17.67 seizures per month for high-dose fish oil and 18.34 seizures per month for placebo. This represents a reduction of 33.6% in seizure frequency with low-dose fish oil. In addition, 5 of 20 patients (25%) showed a 50% reduction in seizures only while taking low-dose fish oil, and 2 of 20 (10%) were free of seizures only while taking low-dose fish oil, Dr. DeGiorgio and his associates said (J. Neurol. Neurosurg. Psychiatry 2014 Sept. 8 [doi:10.1136/jnnp-2014-307749]).

The fish oil capsules proved to be safe, with no serious adverse events occurring during the study. One patient died from autopsy-confirmed sudden death in epilepsy during treatment with high-dose fish oil, but the death was deemed unrelated to fish oil.

It is not yet understood why the low-dose treatment produced better results than the high-dose treatment, the researchers noted.

These findings warrant confirmation in a large, multicenter trial. And it remains to be seen whether this beneficial effect is sustained over time, since the treatment period in this trial was only 10 weeks.

This study was supported by grants from the National Center for Complementary and Alternative Medicine, UCLA’s General Clinical Research Center, and individual donations. Marijo Clark and Pharmavite provided the fish oil and placebo capsules. Dr. DeGiorgio reported no conflicts of interest. An associate disclosed part-time employment with NeuroSigma, which develops devices for epilepsy and other disorders.

Daily low-dose fish oil capsules reduced seizure frequency by 33.6% in patients with drug-resistant epilepsy in a single-center, randomized, phase II trial.

The report was published Sept. 8 in the Journal of Neurology, Neurosurgery, and Psychiatry.

The magnitude of this effect was similar to that seen in many studies of antiepileptic drugs. Moreover, low-dose fish oil may also yield cardiovascular benefits in this patient population, "a finding of some importance given the recent data that the risk of death due to myocardial infarction is significantly higher in people with epilepsy" than in the general population, said Dr. Christopher M. DeGiorgio of the department of neurology at the University of California, Los Angeles, and his associates.

©Clayton Hansen/iStockphoto

The n-3 fatty acids in fish oil are thought to modify calcium and sodium channels in the brain, reducing membrane excitability in neurons. So far, the results of studies of high-dose fish oil as a treatment for epilepsy have been "promising yet inconclusive." This double-blind, crossover trial compared low-dose and high-dose fish oil and placebo in 25 adults with a mean age of 33 years. At baseline, they had three or more localization-related partial onset or generalized tonic/clonic seizures per month and had failed to respond to at least three antiepileptic drugs.

Each oral gel capsule contained either 216 mg of eicosapentaenoic acid (EPA) and 144 mg of docosahexaenoic acid (DHA), for a total of 360 mg of n-3 fatty acids, or a matching placebo capsule filled with corn oil. All study patients took three fish oil capsules per day (low-dose period), three fish oil capsules twice a day (high-dose period), or placebo capsules (control period) for 10 weeks, with 6-week washout periods between each course, for a total study length of 42 weeks.

The primary endpoint, the average seizure frequency, was 12.18 per month during low-dose fish oil therapy, compared with 17.67 seizures per month for high-dose fish oil and 18.34 seizures per month for placebo. This represents a reduction of 33.6% in seizure frequency with low-dose fish oil. In addition, 5 of 20 patients (25%) showed a 50% reduction in seizures only while taking low-dose fish oil, and 2 of 20 (10%) were free of seizures only while taking low-dose fish oil, Dr. DeGiorgio and his associates said (J. Neurol. Neurosurg. Psychiatry 2014 Sept. 8 [doi:10.1136/jnnp-2014-307749]).

The fish oil capsules proved to be safe, with no serious adverse events occurring during the study. One patient died from autopsy-confirmed sudden death in epilepsy during treatment with high-dose fish oil, but the death was deemed unrelated to fish oil.

It is not yet understood why the low-dose treatment produced better results than the high-dose treatment, the researchers noted.

These findings warrant confirmation in a large, multicenter trial. And it remains to be seen whether this beneficial effect is sustained over time, since the treatment period in this trial was only 10 weeks.

This study was supported by grants from the National Center for Complementary and Alternative Medicine, UCLA’s General Clinical Research Center, and individual donations. Marijo Clark and Pharmavite provided the fish oil and placebo capsules. Dr. DeGiorgio reported no conflicts of interest. An associate disclosed part-time employment with NeuroSigma, which develops devices for epilepsy and other disorders.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, a study shows.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those under who were aged 65 years. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

The investigators examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly.

The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were over age 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic workups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 individuals aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline.

All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under-65 group and 94.3% in the over-65 group. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%).

Five-year lung cancer–specific survival was only modestly higher for the under-65 group (64%) than for the over-65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi: 10.7326/M14-1484]).

Similar proportions of each group underwent lung resection – 75.6% of the under-65 patients and 73.2% of the over-65 patients. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the younger group and 1.0% in the older group. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the “harm” side of the balance, the percentage of false-positive results was higher in the older patients (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under-65 group and 8.5% for the over-65 group.

“It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

“Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed,” Dr. Pinsky and his associates wrote. They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. “This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening,” they noted.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, a study shows.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those under who were aged 65 years. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

The investigators examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly.

The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were over age 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic workups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 individuals aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline.

All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under-65 group and 94.3% in the over-65 group. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%).

Five-year lung cancer–specific survival was only modestly higher for the under-65 group (64%) than for the over-65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi: 10.7326/M14-1484]).

Similar proportions of each group underwent lung resection – 75.6% of the under-65 patients and 73.2% of the over-65 patients. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the younger group and 1.0% in the older group. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the “harm” side of the balance, the percentage of false-positive results was higher in the older patients (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under-65 group and 8.5% for the over-65 group.

“It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

“Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed,” Dr. Pinsky and his associates wrote. They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. “This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening,” they noted.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, a study shows.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those under who were aged 65 years. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

The investigators examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly.

The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were over age 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic workups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 individuals aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline.

All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under-65 group and 94.3% in the over-65 group. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%).

Five-year lung cancer–specific survival was only modestly higher for the under-65 group (64%) than for the over-65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi: 10.7326/M14-1484]).

Similar proportions of each group underwent lung resection – 75.6% of the under-65 patients and 73.2% of the over-65 patients. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the younger group and 1.0% in the older group. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the “harm” side of the balance, the percentage of false-positive results was higher in the older patients (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under-65 group and 8.5% for the over-65 group.

“It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

“Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed,” Dr. Pinsky and his associates wrote. They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. “This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening,” they noted.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, according to a report published online Sept. 8 in the Annals of Internal Medicine.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those younger than 65. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

They examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly. The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were older than 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic work-ups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline. All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under 65 and 94.3% in the over 65 groups. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%). Five-year lung cancer–specific survival was only modestly higher for the under 65 group (64%) than for the over 65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi10.7326/M14-1484 ]).

Similar proportions of each group underwent lung resection – 75.6% of the under 65 and 73.2% of the over 65 groups. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the under 65 and 1.0% in the over 65 groups. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the "harm" side of the balance, the percentage of false-positive results was higher in the older group (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under 65 group and 8.5% for the over 65 group.

"It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

"Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed," Dr. Pinsky and his associates wrote.

They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. "This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening," they said.

This study was supported by the National Cancer Institute. Dr. Pinsky had no relevant disclosures to report and coauthors reported financial disclosures involving the NCI and various biotechnology companies.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, according to a report published online Sept. 8 in the Annals of Internal Medicine.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those younger than 65. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

They examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly. The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were older than 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic work-ups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline. All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under 65 and 94.3% in the over 65 groups. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%). Five-year lung cancer–specific survival was only modestly higher for the under 65 group (64%) than for the over 65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi10.7326/M14-1484 ]).

Similar proportions of each group underwent lung resection – 75.6% of the under 65 and 73.2% of the over 65 groups. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the under 65 and 1.0% in the over 65 groups. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the "harm" side of the balance, the percentage of false-positive results was higher in the older group (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under 65 group and 8.5% for the over 65 group.

"It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

"Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed," Dr. Pinsky and his associates wrote.

They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. "This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening," they said.

This study was supported by the National Cancer Institute. Dr. Pinsky had no relevant disclosures to report and coauthors reported financial disclosures involving the NCI and various biotechnology companies.

High-risk patients older than 65 years derive slightly more benefit from low-dose CT screening for lung cancer than younger patients do, according to a report published online Sept. 8 in the Annals of Internal Medicine.

In a secondary analysis of data from the National Lung Screening Trial, low-dose CT (LDCT) screening’s positive predictive value, a measure of screening efficiency, was higher in older patients than in those younger than 65. However, older patients also had slightly greater harms from LDCT screening, mainly because of a slightly higher rate of false-positive results, said Paul F. Pinsky, Ph.D., of the National Cancer Institute and his associates.

They examined this issue because the Centers for Medicare & Medicaid Services has raised the question of whether to cover LDCT costs in this age group, citing concerns that harms may outweigh benefits in the elderly. The National Lung Screening Trial was the primary source of evidence that the screening reduces lung cancer–specific mortality in patients aged 55-74 years, but only 25% of the participants were older than 65. It has been proposed that older patients, who tend to have more comorbid conditions than younger patients, might incur more complications from diagnostic work-ups, might be less eligible for curative surgery for screen-detected cancer, and might have elevated postsurgical mortality, which could tip the balance away from benefit and toward harm.

Dr. Pinsky and his associates assessed several facets of LDCT screening according to the age of the participants, comparing the National Lung Screening Trial’s findings for 19,612 aged 55-64 years against those for 7,110 patients aged 65-74 years at baseline. All the participants underwent three annual LDCT screens and were followed for a median of 6.5 years to ascertain lung cancer mortality.

The sensitivity of LDCT in detecting lung cancers was similar between the two age groups, at 93.2% in the under 65 and 94.3% in the over 65 groups. LDCT’s positive predictive value was significantly higher in the older group (4.9%) than in the younger group (3.0%), mainly because the older group had a substantially higher prevalence of lung cancer (1.5% vs 0.7%). Five-year lung cancer–specific survival was only modestly higher for the under 65 group (64%) than for the over 65 group (55%), the investigators reported (Ann. Intern. Med. 2014 Sept. 8 [doi10.7326/M14-1484 ]).

Similar proportions of each group underwent lung resection – 75.6% of the under 65 and 73.2% of the over 65 groups. In addition, postsurgical mortality at 90 days was similarly low, at 1.8% in the under 65 and 1.0% in the over 65 groups. So the concern that many more older than younger patients would be ineligible for curative surgery proved to be unfounded, as did the concern that older patients would experience significantly more harm from resection than younger patients.

On the "harm" side of the balance, the percentage of false-positive results was higher in the older group (27.7% vs 22.0%), and invasive procedures after false-positive results were slightly more frequent as well (3.3% vs 2.7%). However, the rates of complications resulting from these procedures were similarly low, at 9.8% for the under 65 group and 8.5% for the over 65 group.

"It is difficult to predict how LDCT screening for lung cancer will disseminate in the Medicare-eligible population, regardless of whether it is covered by Medicare. Its use may spread to persons with little chance of benefit and some chance of harm, although this risk exists for those in younger age groups as well.

"Going forward, monitoring and assessing the relative performance of LDCT screening in older persons will be critical to more fully understand its risks and benefits when it is done outside the clinical trial setting, and to modify recommendations on the basis of evidence, if needed," Dr. Pinsky and his associates wrote.

They added that their analysis was limited by the fact that the upper age limit in the National Lung Screening Trial was only 74 years. "This precluded analysis of how persons in their later 70s and 80s fared with LDCT screening," they said.

This study was supported by the National Cancer Institute. Dr. Pinsky had no relevant disclosures to report and coauthors reported financial disclosures involving the NCI and various biotechnology companies.

Most nursing home residents with advanced dementia receive "medications of questionable benefit," given that they are terminally ill and that the goal of their care should be comfort rather than long-term prevention, according to a report published online Sept. 8 in JAMA Internal Medicine.

Researchers analyzed data from a long-term-care pharmacy that serves about half of the 1.3 million residents of nursing homes across the country to characterize the use of medications that have been deemed "never appropriate" in this patient population: cholinesterase inhibitors, memantine, antiplatelet agents other than aspirin, lipid-lowering drugs, sex hormones, hormone antagonists, leukotriene inhibitors, cytotoxic chemotherapy, and immunomodulators. This cross-sectional study comprised a nationally representative sample of 5,406 nursing home residents, and the outcome of interest was prescription of any of these agents during a 90-day observation period, said Dr. Jennifer Tjia of the department of quantitative health sciences, University of Massachusetts, Worcester, and her associates.

© iofoto/Thinkstock

A total of 2,911 (53.9%) of these patients received at least one drug of questionable benefit, with the prevalence ranging from a low of 45% in the mid-Atlantic region to a high of 65% in the West South Central region of the United States. The most frequently used unnecessary medications were cholinesterase inhibitors (36%) and memantine (25%), which are typically given in early dementia to delay or prevent institutionalization – clearly not the treatment goal for this nursing home population. Another 22% of the patients received lipid-lowering agents and 7% received antiplatelet drugs, which are intended to prevent long-term cardiovascular complications – not beneficial in those with limited life expectancy, the researchers said (JAMA Intern. Med. 2014 Sept. 8 [doi:10.1001/jamainternmed.2014.4103]).

Moreover, well known adverse effects of cholinesterase inhibitors and memantine include syncope, hip fracture, arrhythmia, and urinary retention; adverse effects of statins in the elderly include myopathy, memory loss, confusion, elevated blood glucose, and diabetes.

"Despite standards of care that call for minimizing interventions that are unnecessary or provide little benefit in order to focus on interventions that optimize quality of life, polypharmacy remains common in this population." Oral medications are a particular burden for dementia patients, who frequently have swallowing difficulties, and adverse drug effects are a particular burden because these patients have difficulty expressing the symptoms they feel, Dr. Tjia and her associates noted.

The mean 90-day drug expenditure was significantly higher for nursing home patients who received these agents of questionable benefit than for those who did not. And more than 35% of their drug costs, $816 per resident per quarter, was attributable to these unnecessary medications.

This study was supported by the Agency for Healthcare Research and Quality and the National Institute on Aging. Dr. Tjia reported no financial conflicts of interest; one of her associates reported receiving grants from Daiichi Sankyo.

Most nursing home residents with advanced dementia receive "medications of questionable benefit," given that they are terminally ill and that the goal of their care should be comfort rather than long-term prevention, according to a report published online Sept. 8 in JAMA Internal Medicine.

Researchers analyzed data from a long-term-care pharmacy that serves about half of the 1.3 million residents of nursing homes across the country to characterize the use of medications that have been deemed "never appropriate" in this patient population: cholinesterase inhibitors, memantine, antiplatelet agents other than aspirin, lipid-lowering drugs, sex hormones, hormone antagonists, leukotriene inhibitors, cytotoxic chemotherapy, and immunomodulators. This cross-sectional study comprised a nationally representative sample of 5,406 nursing home residents, and the outcome of interest was prescription of any of these agents during a 90-day observation period, said Dr. Jennifer Tjia of the department of quantitative health sciences, University of Massachusetts, Worcester, and her associates.

© iofoto/Thinkstock

A total of 2,911 (53.9%) of these patients received at least one drug of questionable benefit, with the prevalence ranging from a low of 45% in the mid-Atlantic region to a high of 65% in the West South Central region of the United States. The most frequently used unnecessary medications were cholinesterase inhibitors (36%) and memantine (25%), which are typically given in early dementia to delay or prevent institutionalization – clearly not the treatment goal for this nursing home population. Another 22% of the patients received lipid-lowering agents and 7% received antiplatelet drugs, which are intended to prevent long-term cardiovascular complications – not beneficial in those with limited life expectancy, the researchers said (JAMA Intern. Med. 2014 Sept. 8 [doi:10.1001/jamainternmed.2014.4103]).

Moreover, well known adverse effects of cholinesterase inhibitors and memantine include syncope, hip fracture, arrhythmia, and urinary retention; adverse effects of statins in the elderly include myopathy, memory loss, confusion, elevated blood glucose, and diabetes.

"Despite standards of care that call for minimizing interventions that are unnecessary or provide little benefit in order to focus on interventions that optimize quality of life, polypharmacy remains common in this population." Oral medications are a particular burden for dementia patients, who frequently have swallowing difficulties, and adverse drug effects are a particular burden because these patients have difficulty expressing the symptoms they feel, Dr. Tjia and her associates noted.

The mean 90-day drug expenditure was significantly higher for nursing home patients who received these agents of questionable benefit than for those who did not. And more than 35% of their drug costs, $816 per resident per quarter, was attributable to these unnecessary medications.

This study was supported by the Agency for Healthcare Research and Quality and the National Institute on Aging. Dr. Tjia reported no financial conflicts of interest; one of her associates reported receiving grants from Daiichi Sankyo.

Most nursing home residents with advanced dementia receive "medications of questionable benefit," given that they are terminally ill and that the goal of their care should be comfort rather than long-term prevention, according to a report published online Sept. 8 in JAMA Internal Medicine.

Researchers analyzed data from a long-term-care pharmacy that serves about half of the 1.3 million residents of nursing homes across the country to characterize the use of medications that have been deemed "never appropriate" in this patient population: cholinesterase inhibitors, memantine, antiplatelet agents other than aspirin, lipid-lowering drugs, sex hormones, hormone antagonists, leukotriene inhibitors, cytotoxic chemotherapy, and immunomodulators. This cross-sectional study comprised a nationally representative sample of 5,406 nursing home residents, and the outcome of interest was prescription of any of these agents during a 90-day observation period, said Dr. Jennifer Tjia of the department of quantitative health sciences, University of Massachusetts, Worcester, and her associates.

© iofoto/Thinkstock

A total of 2,911 (53.9%) of these patients received at least one drug of questionable benefit, with the prevalence ranging from a low of 45% in the mid-Atlantic region to a high of 65% in the West South Central region of the United States. The most frequently used unnecessary medications were cholinesterase inhibitors (36%) and memantine (25%), which are typically given in early dementia to delay or prevent institutionalization – clearly not the treatment goal for this nursing home population. Another 22% of the patients received lipid-lowering agents and 7% received antiplatelet drugs, which are intended to prevent long-term cardiovascular complications – not beneficial in those with limited life expectancy, the researchers said (JAMA Intern. Med. 2014 Sept. 8 [doi:10.1001/jamainternmed.2014.4103]).

Moreover, well known adverse effects of cholinesterase inhibitors and memantine include syncope, hip fracture, arrhythmia, and urinary retention; adverse effects of statins in the elderly include myopathy, memory loss, confusion, elevated blood glucose, and diabetes.

"Despite standards of care that call for minimizing interventions that are unnecessary or provide little benefit in order to focus on interventions that optimize quality of life, polypharmacy remains common in this population." Oral medications are a particular burden for dementia patients, who frequently have swallowing difficulties, and adverse drug effects are a particular burden because these patients have difficulty expressing the symptoms they feel, Dr. Tjia and her associates noted.

The mean 90-day drug expenditure was significantly higher for nursing home patients who received these agents of questionable benefit than for those who did not. And more than 35% of their drug costs, $816 per resident per quarter, was attributable to these unnecessary medications.

This study was supported by the Agency for Healthcare Research and Quality and the National Institute on Aging. Dr. Tjia reported no financial conflicts of interest; one of her associates reported receiving grants from Daiichi Sankyo.

The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.

The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).

In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.

The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.

Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).

"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).

Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.

"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.

Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.

The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.

The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).

In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.

The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.

Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).

"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).

Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.

"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.

Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.

The controversial 2013 American Heart Association/American College of Cardiology guideline on the assessment of cardiovascular risk matches statin use to patients’ total plaque burden better than did its predecessor, the 2001 National Cholesterol Education Program Adult Treatment Panel III recommendation, according to a retrospective study published online Aug. 25 in the Journal of the American College of Cardiology.

The new guideline assigned statins to more patients who had high plaque burden and fewer patients with no identifiable plaque while increasing overall statin assignment by 15%. The new guideline met considerable resistance on its release, with warnings that statins would be overused and that the tool used to calculate the 10-year probability of an atherosclerotic cardiovascular event overestimated the risk by 75%-150% (Lancet 2013;382:1762-5).

In the study, which involved 3,076 adults who underwent CT angiography in a 5-year period at a single private outpatient radiology practice, the probability that each patient would be prescribed statin therapy was calculated using both the newer guideline on the assessment of cardiovascular risk (J. Am. Coll. Cardiol. 2014;63:2889-934) and the older ATP III recommendations (JAMA 2001;285:2486-97). This probability was then matched to each patient’s actual burden of coronary atherosclerosis, as measured by the CT angiography.

The ACC/AHA guideline outperformed the ATP III guideline substantially at appropriately matching statin therapy with actual plaque burden, said Dr. Kevin M. Johnson of the department of diagnostic radiology at Yale University, New Haven, and Dr. David A. Dowe of Atlantic Medical Imaging in Galloway, N.J.

Among all patients who proved to have heavy plaque, 92% would have been advised to use statin therapy according to the 2013 ACC/AHA guideline, compared with only 53% who would have been advised to use statin therapy according to ATP III. At the same time, among patients found to have no plaque or only trace levels of plaque, fewer would have been prescribed statin therapy according to the ACC/AHA guideline (36%) than according to the ATP III recommendations (41%).

"Of note, under the [ATP III] guideline, 59% of the patients with 50% or greater stenosis of the left main coronary artery and 40% of patients with 50% or greater stenosis of other branches would not have been treated [with statins]. The [respective] results for the [ACC/AHA guidelines] were 18% and 10%," the investigators said (J. Am. Coll. Cardiol. 2014 Aug. 25 [doi:10.1016/j.jacc.214.05.056]).

Overall, 15% more patients would have been assigned statins under the new guideline than with ATP III. This "modest" increase is in line with projections by the ACC/AHA Task Force on Practice Guidelines.

"On the basis of our findings, it is a reasonable hypothesis that the new guideline will better predict coronary events, given that it better correlates with the severity of underlying atherosclerosis," Dr. Johnson and Dr. Dowe noted.

Dr. Johnson and Dr. Dowe reported no relevant financial conflicts of interest.

Detection of AR-V7 in the peripheral blood appears to be a marker of resistance to both enzalutamide and abiraterone treatment in men who have metastatic castration-resistant prostate cancer, according to a report published online Sept. 3 in the New England Journal of Medicine.

In a blinded prospective study involving 62 patients, researchers explored whether the presence of AR-V7 (androgen-receptor splice variant 7 messenger RNA) in circulating tumor cells would predict resistance to enzalutamide and abiraterone, two new agents that act on different molecular pathways to inhibit androgen-receptor signaling. If their findings are confirmed in larger studies, "it is possible that AR-V7 could be used as a biomarker to predict resistance ... and to facilitate treatment selection," reported Dr. Emmanuel S. Antonarakis of Johns Hopkins University, Baltimore, and his associates.

However, it is important to note that these results do not demonstrate a causal role for AR-V7 in mediating resistance to enzalutamide or abiraterone. It is possible that AR-V7 is simply a marker of more advanced disease or a higher disease burden, the investigators added.

The two drugs "represent important advances in the management of castration-resistant prostate cancer." But a substantial proportion of patients don’t benefit from them, "and a clearer understanding of the mechanisms underlying resistance to these drugs would facilitate selection of alternative therapies for such patients," Dr. Antonarakis and his associates said.

In this study, men with metastatic castration-resistant prostate cancer who were about to begin standard treatment with enzalutamide (31 patients) or abiraterone (31 patients) provided peripheral blood samples for analysis of circulating tumor cells at baseline.

After a median follow-up of approximately 5 months, the prostate-specific antigen (PSA) response in the enzalutamide group was 0% among men who were AR-V7 positive, compared with 53% among men who were AR-V7 negative. In the abiraterone group, the PSA response was 0% among men who were AR-V7 positive, compared with 68% among men who were AR-V7 negative. Not one of the AR-V7-positive patients showed any appreciable clinical benefit from these drugs, the investigators reported (New Engl. J. Med. 2014 Sept. 3 [doi: 10.1056/NEJMoa1315815]).

In addition, progression-free survival was shorter among AR-V7-positive men than among men who had no detectable AR-V7, whether that endpoint was measured by PSA level, radiography, or clinical signs and symptoms.

This study was supported by the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Research Program, and the National Institutes of Health. Dr. Antonarakis reported receiving personal fees from Sanofi, Dendreon, and Janssen Biotech, and his associates reported ties to numerous industry sources.

Detection of AR-V7 in the peripheral blood appears to be a marker of resistance to both enzalutamide and abiraterone treatment in men who have metastatic castration-resistant prostate cancer, according to a report published online Sept. 3 in the New England Journal of Medicine.

In a blinded prospective study involving 62 patients, researchers explored whether the presence of AR-V7 (androgen-receptor splice variant 7 messenger RNA) in circulating tumor cells would predict resistance to enzalutamide and abiraterone, two new agents that act on different molecular pathways to inhibit androgen-receptor signaling. If their findings are confirmed in larger studies, "it is possible that AR-V7 could be used as a biomarker to predict resistance ... and to facilitate treatment selection," reported Dr. Emmanuel S. Antonarakis of Johns Hopkins University, Baltimore, and his associates.

However, it is important to note that these results do not demonstrate a causal role for AR-V7 in mediating resistance to enzalutamide or abiraterone. It is possible that AR-V7 is simply a marker of more advanced disease or a higher disease burden, the investigators added.

The two drugs "represent important advances in the management of castration-resistant prostate cancer." But a substantial proportion of patients don’t benefit from them, "and a clearer understanding of the mechanisms underlying resistance to these drugs would facilitate selection of alternative therapies for such patients," Dr. Antonarakis and his associates said.

In this study, men with metastatic castration-resistant prostate cancer who were about to begin standard treatment with enzalutamide (31 patients) or abiraterone (31 patients) provided peripheral blood samples for analysis of circulating tumor cells at baseline.

After a median follow-up of approximately 5 months, the prostate-specific antigen (PSA) response in the enzalutamide group was 0% among men who were AR-V7 positive, compared with 53% among men who were AR-V7 negative. In the abiraterone group, the PSA response was 0% among men who were AR-V7 positive, compared with 68% among men who were AR-V7 negative. Not one of the AR-V7-positive patients showed any appreciable clinical benefit from these drugs, the investigators reported (New Engl. J. Med. 2014 Sept. 3 [doi: 10.1056/NEJMoa1315815]).

In addition, progression-free survival was shorter among AR-V7-positive men than among men who had no detectable AR-V7, whether that endpoint was measured by PSA level, radiography, or clinical signs and symptoms.

This study was supported by the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Research Program, and the National Institutes of Health. Dr. Antonarakis reported receiving personal fees from Sanofi, Dendreon, and Janssen Biotech, and his associates reported ties to numerous industry sources.

Detection of AR-V7 in the peripheral blood appears to be a marker of resistance to both enzalutamide and abiraterone treatment in men who have metastatic castration-resistant prostate cancer, according to a report published online Sept. 3 in the New England Journal of Medicine.

In a blinded prospective study involving 62 patients, researchers explored whether the presence of AR-V7 (androgen-receptor splice variant 7 messenger RNA) in circulating tumor cells would predict resistance to enzalutamide and abiraterone, two new agents that act on different molecular pathways to inhibit androgen-receptor signaling. If their findings are confirmed in larger studies, "it is possible that AR-V7 could be used as a biomarker to predict resistance ... and to facilitate treatment selection," reported Dr. Emmanuel S. Antonarakis of Johns Hopkins University, Baltimore, and his associates.

However, it is important to note that these results do not demonstrate a causal role for AR-V7 in mediating resistance to enzalutamide or abiraterone. It is possible that AR-V7 is simply a marker of more advanced disease or a higher disease burden, the investigators added.

The two drugs "represent important advances in the management of castration-resistant prostate cancer." But a substantial proportion of patients don’t benefit from them, "and a clearer understanding of the mechanisms underlying resistance to these drugs would facilitate selection of alternative therapies for such patients," Dr. Antonarakis and his associates said.

In this study, men with metastatic castration-resistant prostate cancer who were about to begin standard treatment with enzalutamide (31 patients) or abiraterone (31 patients) provided peripheral blood samples for analysis of circulating tumor cells at baseline.

After a median follow-up of approximately 5 months, the prostate-specific antigen (PSA) response in the enzalutamide group was 0% among men who were AR-V7 positive, compared with 53% among men who were AR-V7 negative. In the abiraterone group, the PSA response was 0% among men who were AR-V7 positive, compared with 68% among men who were AR-V7 negative. Not one of the AR-V7-positive patients showed any appreciable clinical benefit from these drugs, the investigators reported (New Engl. J. Med. 2014 Sept. 3 [doi: 10.1056/NEJMoa1315815]).

In addition, progression-free survival was shorter among AR-V7-positive men than among men who had no detectable AR-V7, whether that endpoint was measured by PSA level, radiography, or clinical signs and symptoms.

This study was supported by the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Research Program, and the National Institutes of Health. Dr. Antonarakis reported receiving personal fees from Sanofi, Dendreon, and Janssen Biotech, and his associates reported ties to numerous industry sources.

Continuous administration of lenolidamide plus dexamethasone significantly extended progression-free survival in older patients with newly diagnosed multiple myeloma, compared with the standard, fixed regimen of melphalan and prednisone combined with thalidomide, in a phase III randomized trial reported online Sept. 4 in the New England Journal of Medicine.

The open-label study involved patients aged 65 years and older who weren’t eligible for stem-cell transplantation. A total of 35% of the participants were over age 75, and many had more advanced disease than has been allowed in previous clinical trials of melphalan/prednisone/thalidomide (MPT), said Dr. Lotfi Benboubker of the hematology and cellular therapy service, Central Regional University Hospital, Tours, France, and his associates.

The 1,623 patients were enrolled during a 3-year period at 246 medical centers in 18 countries in Europe, North America, and the Asia-Pacific region. They were randomly assigned to receive unlimited lenalidomide/dexamethasone in 28-day cycles until disease progression (535 patients), 18 rounds of lenalidomide/dexamethasone in 28-day cycles for 72 weeks (541 patients), or 12 rounds of MPT in 42-day cycles for 72 weeks (547 patients). All patients received antithrombotic prophylaxis as specified in the study protocol, as well as bisphosphonates and other supportive therapies at the investigator’s discretion.

The median duration of follow-up was 37.0 months (range, 0-56.7 months). A total of 39% of the patients in the continuous lenalidomide group received more than 2 years of treatment.

The primary efficacy endpoint, progression-free survival, was 25.5 months with continuous lenalidomide, which was significantly (28%) longer than the 20.7 months with fixed lenalidomide and 21.2 months with MPT, the investigators reported (N. Engl. J. Med. 2014;371:906-17).

Rates of overall survival in the three study groups were 70%, 66%, and 62% at 3 years and 59%, 56%, and 51% at 4 years, for continuous lenalidomide, fixed lenalidomide, and MPT, respectively. "Although the difference in overall survival did not cross the prespecified superiority boundary, continuous lenalidomide/dexamethasone reduced the risk of death, as compared with MPT (hazard ratio, 0.78)," they noted.

Secondary outcomes such as treatment response rates, rates of complete response, and durability of response all were higher with continuous lenalidomide than with fixed lenalidomide or MPT. Continuous lenalidomide also was superior regarding two exploratory outcomes: need for second-line therapy and time to second-line therapy. "This represents a clinically significant advantage, especially for elderly patients, in whom a response to rescue therapy at the time of first relapse may be difficult to achieve," Dr. Benboubker and his associates said.

As expected, both lenalidomide groups had lower rates of hematologic toxic events than the MPT group, but both also had higher rates of infection. The incidence of second primary cancers was higher with MPT than with lenalidomide.

This study was funded by Celgene, maker of lenolidamide, which also took part in study design, data collection, data analysis, and manuscript preparation. Dr. Benboubker reported ties to Celgene, Millennium, Onyx Therapeutics, and Lilly; his associates reported ties to numerous industry sources.

Continuous administration of lenolidamide plus dexamethasone significantly extended progression-free survival in older patients with newly diagnosed multiple myeloma, compared with the standard, fixed regimen of melphalan and prednisone combined with thalidomide, in a phase III randomized trial reported online Sept. 4 in the New England Journal of Medicine.

The open-label study involved patients aged 65 years and older who weren’t eligible for stem-cell transplantation. A total of 35% of the participants were over age 75, and many had more advanced disease than has been allowed in previous clinical trials of melphalan/prednisone/thalidomide (MPT), said Dr. Lotfi Benboubker of the hematology and cellular therapy service, Central Regional University Hospital, Tours, France, and his associates.

The 1,623 patients were enrolled during a 3-year period at 246 medical centers in 18 countries in Europe, North America, and the Asia-Pacific region. They were randomly assigned to receive unlimited lenalidomide/dexamethasone in 28-day cycles until disease progression (535 patients), 18 rounds of lenalidomide/dexamethasone in 28-day cycles for 72 weeks (541 patients), or 12 rounds of MPT in 42-day cycles for 72 weeks (547 patients). All patients received antithrombotic prophylaxis as specified in the study protocol, as well as bisphosphonates and other supportive therapies at the investigator’s discretion.

The median duration of follow-up was 37.0 months (range, 0-56.7 months). A total of 39% of the patients in the continuous lenalidomide group received more than 2 years of treatment.

The primary efficacy endpoint, progression-free survival, was 25.5 months with continuous lenalidomide, which was significantly (28%) longer than the 20.7 months with fixed lenalidomide and 21.2 months with MPT, the investigators reported (N. Engl. J. Med. 2014;371:906-17).

Rates of overall survival in the three study groups were 70%, 66%, and 62% at 3 years and 59%, 56%, and 51% at 4 years, for continuous lenalidomide, fixed lenalidomide, and MPT, respectively. "Although the difference in overall survival did not cross the prespecified superiority boundary, continuous lenalidomide/dexamethasone reduced the risk of death, as compared with MPT (hazard ratio, 0.78)," they noted.

Secondary outcomes such as treatment response rates, rates of complete response, and durability of response all were higher with continuous lenalidomide than with fixed lenalidomide or MPT. Continuous lenalidomide also was superior regarding two exploratory outcomes: need for second-line therapy and time to second-line therapy. "This represents a clinically significant advantage, especially for elderly patients, in whom a response to rescue therapy at the time of first relapse may be difficult to achieve," Dr. Benboubker and his associates said.

As expected, both lenalidomide groups had lower rates of hematologic toxic events than the MPT group, but both also had higher rates of infection. The incidence of second primary cancers was higher with MPT than with lenalidomide.

This study was funded by Celgene, maker of lenolidamide, which also took part in study design, data collection, data analysis, and manuscript preparation. Dr. Benboubker reported ties to Celgene, Millennium, Onyx Therapeutics, and Lilly; his associates reported ties to numerous industry sources.

Continuous administration of lenolidamide plus dexamethasone significantly extended progression-free survival in older patients with newly diagnosed multiple myeloma, compared with the standard, fixed regimen of melphalan and prednisone combined with thalidomide, in a phase III randomized trial reported online Sept. 4 in the New England Journal of Medicine.

The open-label study involved patients aged 65 years and older who weren’t eligible for stem-cell transplantation. A total of 35% of the participants were over age 75, and many had more advanced disease than has been allowed in previous clinical trials of melphalan/prednisone/thalidomide (MPT), said Dr. Lotfi Benboubker of the hematology and cellular therapy service, Central Regional University Hospital, Tours, France, and his associates.

The 1,623 patients were enrolled during a 3-year period at 246 medical centers in 18 countries in Europe, North America, and the Asia-Pacific region. They were randomly assigned to receive unlimited lenalidomide/dexamethasone in 28-day cycles until disease progression (535 patients), 18 rounds of lenalidomide/dexamethasone in 28-day cycles for 72 weeks (541 patients), or 12 rounds of MPT in 42-day cycles for 72 weeks (547 patients). All patients received antithrombotic prophylaxis as specified in the study protocol, as well as bisphosphonates and other supportive therapies at the investigator’s discretion.

The median duration of follow-up was 37.0 months (range, 0-56.7 months). A total of 39% of the patients in the continuous lenalidomide group received more than 2 years of treatment.

The primary efficacy endpoint, progression-free survival, was 25.5 months with continuous lenalidomide, which was significantly (28%) longer than the 20.7 months with fixed lenalidomide and 21.2 months with MPT, the investigators reported (N. Engl. J. Med. 2014;371:906-17).

Rates of overall survival in the three study groups were 70%, 66%, and 62% at 3 years and 59%, 56%, and 51% at 4 years, for continuous lenalidomide, fixed lenalidomide, and MPT, respectively. "Although the difference in overall survival did not cross the prespecified superiority boundary, continuous lenalidomide/dexamethasone reduced the risk of death, as compared with MPT (hazard ratio, 0.78)," they noted.

Secondary outcomes such as treatment response rates, rates of complete response, and durability of response all were higher with continuous lenalidomide than with fixed lenalidomide or MPT. Continuous lenalidomide also was superior regarding two exploratory outcomes: need for second-line therapy and time to second-line therapy. "This represents a clinically significant advantage, especially for elderly patients, in whom a response to rescue therapy at the time of first relapse may be difficult to achieve," Dr. Benboubker and his associates said.

As expected, both lenalidomide groups had lower rates of hematologic toxic events than the MPT group, but both also had higher rates of infection. The incidence of second primary cancers was higher with MPT than with lenalidomide.

This study was funded by Celgene, maker of lenolidamide, which also took part in study design, data collection, data analysis, and manuscript preparation. Dr. Benboubker reported ties to Celgene, Millennium, Onyx Therapeutics, and Lilly; his associates reported ties to numerous industry sources.