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Autism spectrum disorder on the rise, CDC says
The Centers for Disease Control and Prevention estimates that about 1 in 68 U.S. children has autism spectrum disorder, according to findings published March 27 in the agency’s Morbidity and Mortality Weekly Report. This is a 30% increase from CDC’s estimate of 1 in 88 children, using 2008 data.
The findings also show that autism spectrum disorder (ASD) continues to be more prevalent in boys than in girls: 1 in 42 boys had ASD in the latest report, compared with 1 in 189 girls (MMWR Surveill. Summ. 2014 March 27;63:1-21).
The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination, Dr. Coleen Boyle, director of CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD), said in a teleconference.
CDC looked at 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of ASD prevalence in children aged 8 years in 11 different sites in the United States, based on records from community sources that diagnose and provide services to children with developmental disabilities.
Of the 11 sites studied, 7 had information available on intellectual ability of at least 70% of children with ASD. Of the 3,604 children with available data, 31% were classified as having intellectual disability (IQ of 70 or below), 23% were considered borderline (IQ = 71-85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.
"We recognize now that autism is a spectrum, no longer limited to the severely affected," added Dr. Marshalyn Yeargin-Allsopp, a pediatrician who is chief of the developmental disabilities branch of NCBDDD. "There are children with higher IQs being diagnosed, who may not even be receiving special education services, and the numbers may reflect that."
Non-Hispanic white children were 30% more likely to be identified with ASD than non-Hispanic black children, and were about 50% more likely to have ASD than Hispanic children.
Dr. Boyle stressed the importance of early screening and identification of ASD in children (ASD can be diagnosed by the time a child reaches age 2 years), and urged parents to take action if a child shows any signs of developmental delays.
"Community leaders, health professionals, educators, and childcare providers should use these data to ensure children with autism spectrum disorder are identified as early as possible and connected to the services they need," Dr. Boyle said at the teleconference.
To help promote early intervention in ASD, CDC will be launching an awareness initiative called "Birth to Five, Watch Me Thrive," which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.
"Most children with autism are not diagnosed until after age 4 years," she said. "CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better."
CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census, and comparisons with previous ADDM findings should be interpreted with caution, as ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on post census estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in very broad terms and should not be interpreted as generalizable to all persons within those categories.
The ADDM Network is funded by CDC. No other disclosures were reported.
The Centers for Disease Control and Prevention estimates that about 1 in 68 U.S. children has autism spectrum disorder, according to findings published March 27 in the agency’s Morbidity and Mortality Weekly Report. This is a 30% increase from CDC’s estimate of 1 in 88 children, using 2008 data.
The findings also show that autism spectrum disorder (ASD) continues to be more prevalent in boys than in girls: 1 in 42 boys had ASD in the latest report, compared with 1 in 189 girls (MMWR Surveill. Summ. 2014 March 27;63:1-21).
The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination, Dr. Coleen Boyle, director of CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD), said in a teleconference.
CDC looked at 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of ASD prevalence in children aged 8 years in 11 different sites in the United States, based on records from community sources that diagnose and provide services to children with developmental disabilities.
Of the 11 sites studied, 7 had information available on intellectual ability of at least 70% of children with ASD. Of the 3,604 children with available data, 31% were classified as having intellectual disability (IQ of 70 or below), 23% were considered borderline (IQ = 71-85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.
"We recognize now that autism is a spectrum, no longer limited to the severely affected," added Dr. Marshalyn Yeargin-Allsopp, a pediatrician who is chief of the developmental disabilities branch of NCBDDD. "There are children with higher IQs being diagnosed, who may not even be receiving special education services, and the numbers may reflect that."
Non-Hispanic white children were 30% more likely to be identified with ASD than non-Hispanic black children, and were about 50% more likely to have ASD than Hispanic children.
Dr. Boyle stressed the importance of early screening and identification of ASD in children (ASD can be diagnosed by the time a child reaches age 2 years), and urged parents to take action if a child shows any signs of developmental delays.
"Community leaders, health professionals, educators, and childcare providers should use these data to ensure children with autism spectrum disorder are identified as early as possible and connected to the services they need," Dr. Boyle said at the teleconference.
To help promote early intervention in ASD, CDC will be launching an awareness initiative called "Birth to Five, Watch Me Thrive," which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.
"Most children with autism are not diagnosed until after age 4 years," she said. "CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better."
CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census, and comparisons with previous ADDM findings should be interpreted with caution, as ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on post census estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in very broad terms and should not be interpreted as generalizable to all persons within those categories.
The ADDM Network is funded by CDC. No other disclosures were reported.
The Centers for Disease Control and Prevention estimates that about 1 in 68 U.S. children has autism spectrum disorder, according to findings published March 27 in the agency’s Morbidity and Mortality Weekly Report. This is a 30% increase from CDC’s estimate of 1 in 88 children, using 2008 data.
The findings also show that autism spectrum disorder (ASD) continues to be more prevalent in boys than in girls: 1 in 42 boys had ASD in the latest report, compared with 1 in 189 girls (MMWR Surveill. Summ. 2014 March 27;63:1-21).
The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination, Dr. Coleen Boyle, director of CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD), said in a teleconference.
CDC looked at 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of ASD prevalence in children aged 8 years in 11 different sites in the United States, based on records from community sources that diagnose and provide services to children with developmental disabilities.
Of the 11 sites studied, 7 had information available on intellectual ability of at least 70% of children with ASD. Of the 3,604 children with available data, 31% were classified as having intellectual disability (IQ of 70 or below), 23% were considered borderline (IQ = 71-85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.
"We recognize now that autism is a spectrum, no longer limited to the severely affected," added Dr. Marshalyn Yeargin-Allsopp, a pediatrician who is chief of the developmental disabilities branch of NCBDDD. "There are children with higher IQs being diagnosed, who may not even be receiving special education services, and the numbers may reflect that."
Non-Hispanic white children were 30% more likely to be identified with ASD than non-Hispanic black children, and were about 50% more likely to have ASD than Hispanic children.
Dr. Boyle stressed the importance of early screening and identification of ASD in children (ASD can be diagnosed by the time a child reaches age 2 years), and urged parents to take action if a child shows any signs of developmental delays.
"Community leaders, health professionals, educators, and childcare providers should use these data to ensure children with autism spectrum disorder are identified as early as possible and connected to the services they need," Dr. Boyle said at the teleconference.
To help promote early intervention in ASD, CDC will be launching an awareness initiative called "Birth to Five, Watch Me Thrive," which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.
"Most children with autism are not diagnosed until after age 4 years," she said. "CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better."
CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census, and comparisons with previous ADDM findings should be interpreted with caution, as ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on post census estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in very broad terms and should not be interpreted as generalizable to all persons within those categories.
The ADDM Network is funded by CDC. No other disclosures were reported.
FROM MMWR
Major finding: About 1 in 68 children was identified as having autism spectrum disorder, up from estimates of 1 in 88 children using 2008 data.
Data source: 2010 data collected by CDC’s ADDM Network across 11 sites in the United States.
Disclosures: The ADDM Network is funded by CDC. No other disclosures were reported.
USPSTF: Evidence still ‘insufficient’ to back cognitive impairment screening
Citing an ongoing lack of data about the benefits and harms of screening, the U.S. Preventive Services Task Force has left unchanged the recommendations of its 2003 guidelines on cognitive impairment screening in older adults, according to an update published March 24.
"The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment," Dr. Virginia A. Moyer said in a report on behalf of the USPSTF.
"Evidence on the effect of screening and early detection of mild to moderate dementia on decision making, planning, or other important patient outcomes is a critical gap in the evidence," she added. Other research needs include further study of the harms of screening, new interventions that address the changing needs of patients and families, and interventions that affect the long-term clinical direction of mild to moderate dementia.
In its review, the USPSTF evaluated 55 studies on instruments that screen for cognitive impairment, of which 46 provided evidence on the sensitivity of dementia screening and 27 provided evidence on mild cognitive impairment. Screening tests included a variety of tasks to assess at least one cognitive function, such as memory, attention, language, and visuospatial/executive functioning. The USPSTF looked at studies that used the Mini-Mental State Examination (MMSE), Clock Drawing Test, verbal fluency tests, Informant Questionnaire on Cognitive Decline in the Elderly, Memory Impairment Screen, Mini-Cog Test, Abbreviated Mental Test, and Short Portable Mental Status Questionnaire.
The MMSE was the most evaluated screening tool, with 25 published studies. Mean age of participants ranged from 69 to 95 years, and the mean prevalence of dementia ranged from 1.2% to 38%. The pooled sensitivity from 14 studies for the most commonly reported cut points was 88.3% (95% confidence interval, 81.3%-92.9%), and specificity was 86.2% (CI, 81.8%-89.7%).
Other screening tools that were evaluated "were studied in far fewer studies (four to seven studies each), had limited reproducibility in primary care relevant populations, and had unknown optimum cut points," Dr. Moyer wrote.
In addition, no trials studied the "direct effect of screening" by comparing screened and unscreened patients and reporting important clinical and decision-making outcomes, the report’s authors said. And no studies reported on direct or indirect harms from false-positive or false-negative screening results, psychological harms, unnecessary diagnostic testing, or labeling.
Dementia affects about 2.4 to 5.5 million Americans. Types of dementia in older adults include Alzheimer’s disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, Parkinson’s disease with dementia, and mixed-cause dementia. The USPSTF distinguishes between dementia and mild cognitive impairment, which is less severe and does not considerably interfere with day-to-day activities.
The prevalence of dementia is estimated to be 5% in adults aged 71-79 years of age, 24% in those aged 80-89 years, and 37% in those aged 90 years and older. The prevalence of mild cognitive impairment is more uncertain, and estimates range from 3% to 42% in adults aged 65 years and older.
Although this report differs from the 2003 recommendation because it considers screening and treatment for mild cognitive impairment in addition to dementia, and it includes additional information about the test performance of screening instruments, "the overall evidence is insufficient to make a recommendation on screening," Dr. Moyer said.
Disclosure forms from USPSTF members can be viewed here.
Citing an ongoing lack of data about the benefits and harms of screening, the U.S. Preventive Services Task Force has left unchanged the recommendations of its 2003 guidelines on cognitive impairment screening in older adults, according to an update published March 24.
"The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment," Dr. Virginia A. Moyer said in a report on behalf of the USPSTF.
"Evidence on the effect of screening and early detection of mild to moderate dementia on decision making, planning, or other important patient outcomes is a critical gap in the evidence," she added. Other research needs include further study of the harms of screening, new interventions that address the changing needs of patients and families, and interventions that affect the long-term clinical direction of mild to moderate dementia.
In its review, the USPSTF evaluated 55 studies on instruments that screen for cognitive impairment, of which 46 provided evidence on the sensitivity of dementia screening and 27 provided evidence on mild cognitive impairment. Screening tests included a variety of tasks to assess at least one cognitive function, such as memory, attention, language, and visuospatial/executive functioning. The USPSTF looked at studies that used the Mini-Mental State Examination (MMSE), Clock Drawing Test, verbal fluency tests, Informant Questionnaire on Cognitive Decline in the Elderly, Memory Impairment Screen, Mini-Cog Test, Abbreviated Mental Test, and Short Portable Mental Status Questionnaire.
The MMSE was the most evaluated screening tool, with 25 published studies. Mean age of participants ranged from 69 to 95 years, and the mean prevalence of dementia ranged from 1.2% to 38%. The pooled sensitivity from 14 studies for the most commonly reported cut points was 88.3% (95% confidence interval, 81.3%-92.9%), and specificity was 86.2% (CI, 81.8%-89.7%).
Other screening tools that were evaluated "were studied in far fewer studies (four to seven studies each), had limited reproducibility in primary care relevant populations, and had unknown optimum cut points," Dr. Moyer wrote.
In addition, no trials studied the "direct effect of screening" by comparing screened and unscreened patients and reporting important clinical and decision-making outcomes, the report’s authors said. And no studies reported on direct or indirect harms from false-positive or false-negative screening results, psychological harms, unnecessary diagnostic testing, or labeling.
Dementia affects about 2.4 to 5.5 million Americans. Types of dementia in older adults include Alzheimer’s disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, Parkinson’s disease with dementia, and mixed-cause dementia. The USPSTF distinguishes between dementia and mild cognitive impairment, which is less severe and does not considerably interfere with day-to-day activities.
The prevalence of dementia is estimated to be 5% in adults aged 71-79 years of age, 24% in those aged 80-89 years, and 37% in those aged 90 years and older. The prevalence of mild cognitive impairment is more uncertain, and estimates range from 3% to 42% in adults aged 65 years and older.
Although this report differs from the 2003 recommendation because it considers screening and treatment for mild cognitive impairment in addition to dementia, and it includes additional information about the test performance of screening instruments, "the overall evidence is insufficient to make a recommendation on screening," Dr. Moyer said.
Disclosure forms from USPSTF members can be viewed here.
Citing an ongoing lack of data about the benefits and harms of screening, the U.S. Preventive Services Task Force has left unchanged the recommendations of its 2003 guidelines on cognitive impairment screening in older adults, according to an update published March 24.
"The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment," Dr. Virginia A. Moyer said in a report on behalf of the USPSTF.
"Evidence on the effect of screening and early detection of mild to moderate dementia on decision making, planning, or other important patient outcomes is a critical gap in the evidence," she added. Other research needs include further study of the harms of screening, new interventions that address the changing needs of patients and families, and interventions that affect the long-term clinical direction of mild to moderate dementia.
In its review, the USPSTF evaluated 55 studies on instruments that screen for cognitive impairment, of which 46 provided evidence on the sensitivity of dementia screening and 27 provided evidence on mild cognitive impairment. Screening tests included a variety of tasks to assess at least one cognitive function, such as memory, attention, language, and visuospatial/executive functioning. The USPSTF looked at studies that used the Mini-Mental State Examination (MMSE), Clock Drawing Test, verbal fluency tests, Informant Questionnaire on Cognitive Decline in the Elderly, Memory Impairment Screen, Mini-Cog Test, Abbreviated Mental Test, and Short Portable Mental Status Questionnaire.
The MMSE was the most evaluated screening tool, with 25 published studies. Mean age of participants ranged from 69 to 95 years, and the mean prevalence of dementia ranged from 1.2% to 38%. The pooled sensitivity from 14 studies for the most commonly reported cut points was 88.3% (95% confidence interval, 81.3%-92.9%), and specificity was 86.2% (CI, 81.8%-89.7%).
Other screening tools that were evaluated "were studied in far fewer studies (four to seven studies each), had limited reproducibility in primary care relevant populations, and had unknown optimum cut points," Dr. Moyer wrote.
In addition, no trials studied the "direct effect of screening" by comparing screened and unscreened patients and reporting important clinical and decision-making outcomes, the report’s authors said. And no studies reported on direct or indirect harms from false-positive or false-negative screening results, psychological harms, unnecessary diagnostic testing, or labeling.
Dementia affects about 2.4 to 5.5 million Americans. Types of dementia in older adults include Alzheimer’s disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, Parkinson’s disease with dementia, and mixed-cause dementia. The USPSTF distinguishes between dementia and mild cognitive impairment, which is less severe and does not considerably interfere with day-to-day activities.
The prevalence of dementia is estimated to be 5% in adults aged 71-79 years of age, 24% in those aged 80-89 years, and 37% in those aged 90 years and older. The prevalence of mild cognitive impairment is more uncertain, and estimates range from 3% to 42% in adults aged 65 years and older.
Although this report differs from the 2003 recommendation because it considers screening and treatment for mild cognitive impairment in addition to dementia, and it includes additional information about the test performance of screening instruments, "the overall evidence is insufficient to make a recommendation on screening," Dr. Moyer said.
Disclosure forms from USPSTF members can be viewed here.
FROM A USPSTF REPORT
Childhood glomerular disease associated with adult hypertension
Men who had glomerular disease as children were at increased risk for developing hypertension as adults, according to a study published in JAMA.
Dr. Asaf Vivante and his colleagues studied 38,144 healthy men in the Staff Periodic Examination Center (SPEC) of the Israeli Defense Forces Medical Corps, 264 of whom had a medical history of resolved childhood glomerular disease.
All participants had a baseline evaluation at age 17, during which the diagnosis of resolved childhood glomerular disease (including childhood acute glomerulonephritis and nephrotic syndrome) was determined. Men with unresolved childhood glomerular disease, hypertension, diabetes, active rheumatic diseases, or any other kidney or urinary tract disorders were excluded. SPEC follow-up visits occurred until hypertension diagnosis, retirement from service, or Dec. 31, 2010, whichever came first.
At a mean follow-up of 18 years, 2,856 men developed hypertension. Of men with a history of resolved childhood glomerular disease, 13.6% had hypertension as adults, compared with 7.4% who had no childhood kidney disease (hazard ratio, 1.67; 95% confidence interval, 1.20-2.31; P = .002 when adjusted for age and body mass index) (JAMA 2014;311:1155-7).
The researchers cited a few limitations of the study, including a lack of information on the exact glomerular histopathologic injury during childhood and the young age of the study population at the end of follow-up.
Database access was provided by the Israeli Defense Forces Medical Corps. One coauthor reported receiving travel reimbursement from the European Cooperation in Science and Technology. No other disclosures were reported.
Men who had glomerular disease as children were at increased risk for developing hypertension as adults, according to a study published in JAMA.
Dr. Asaf Vivante and his colleagues studied 38,144 healthy men in the Staff Periodic Examination Center (SPEC) of the Israeli Defense Forces Medical Corps, 264 of whom had a medical history of resolved childhood glomerular disease.
All participants had a baseline evaluation at age 17, during which the diagnosis of resolved childhood glomerular disease (including childhood acute glomerulonephritis and nephrotic syndrome) was determined. Men with unresolved childhood glomerular disease, hypertension, diabetes, active rheumatic diseases, or any other kidney or urinary tract disorders were excluded. SPEC follow-up visits occurred until hypertension diagnosis, retirement from service, or Dec. 31, 2010, whichever came first.
At a mean follow-up of 18 years, 2,856 men developed hypertension. Of men with a history of resolved childhood glomerular disease, 13.6% had hypertension as adults, compared with 7.4% who had no childhood kidney disease (hazard ratio, 1.67; 95% confidence interval, 1.20-2.31; P = .002 when adjusted for age and body mass index) (JAMA 2014;311:1155-7).
The researchers cited a few limitations of the study, including a lack of information on the exact glomerular histopathologic injury during childhood and the young age of the study population at the end of follow-up.
Database access was provided by the Israeli Defense Forces Medical Corps. One coauthor reported receiving travel reimbursement from the European Cooperation in Science and Technology. No other disclosures were reported.
Men who had glomerular disease as children were at increased risk for developing hypertension as adults, according to a study published in JAMA.
Dr. Asaf Vivante and his colleagues studied 38,144 healthy men in the Staff Periodic Examination Center (SPEC) of the Israeli Defense Forces Medical Corps, 264 of whom had a medical history of resolved childhood glomerular disease.
All participants had a baseline evaluation at age 17, during which the diagnosis of resolved childhood glomerular disease (including childhood acute glomerulonephritis and nephrotic syndrome) was determined. Men with unresolved childhood glomerular disease, hypertension, diabetes, active rheumatic diseases, or any other kidney or urinary tract disorders were excluded. SPEC follow-up visits occurred until hypertension diagnosis, retirement from service, or Dec. 31, 2010, whichever came first.
At a mean follow-up of 18 years, 2,856 men developed hypertension. Of men with a history of resolved childhood glomerular disease, 13.6% had hypertension as adults, compared with 7.4% who had no childhood kidney disease (hazard ratio, 1.67; 95% confidence interval, 1.20-2.31; P = .002 when adjusted for age and body mass index) (JAMA 2014;311:1155-7).
The researchers cited a few limitations of the study, including a lack of information on the exact glomerular histopathologic injury during childhood and the young age of the study population at the end of follow-up.
Database access was provided by the Israeli Defense Forces Medical Corps. One coauthor reported receiving travel reimbursement from the European Cooperation in Science and Technology. No other disclosures were reported.
FROM JAMA
Major finding: Of men with a history of resolved childhood glomerular disease, 13.6% developed hypertension as adults, compared with 7.4% of men who had no childhood kidney disease (hazard ratio, 1.67; 95% confidence interval, 1.20-2.31; P = .002 when adjusted for age and body mass index).
Data source: An analysis using Cox proportional hazards models of 38,144 healthy men in the Staff Periodic Examination Center (SPEC) of the Israeli Defense Forces Medical Corps, 264 of whom had a history of resolved childhood glomerular disease.
Disclosures: Database access was provided by the Israeli Defense Forces Medical Corps. One coauthor reported receiving travel reimbursement from the European Cooperation in Science and Technology. No other disclosures were reported.
CDC: Younger adults least likely to be vaccinated and most likely to be hard hit by flu
So far, the 2013-2014 influenza season has been hardest on young and middle-age adults, with 61% of flu hospitalizations occurring in the 18- to 64-year-old age group, the Centers for Disease Control and Prevention reported in this week’s Morbidity and Mortality Weekly Report. This is a drastic jump from the previous season, when this age group accounted for only 35% of hospitalizations.
The report also found that the young adult population has accounted for an increased number of influenza-related deaths than in previous years, with adults aged 25-64 years of age accounting for 60% of flu deaths this season, compared with just 18%, 30%, and 47% for the previous three seasons, respectively (MMWR 2014; 63;137-42).
"Influenza can make anyone really sick, really fast, and it can kill," Dr. Thomas R. Frieden, director of the Centers for Disease Control and Prevention, said in a teleconference. "Vaccination is the single most important thing you can do to protect yourself."
The CDC conducted an interim analysis of flu vaccine effectiveness in 2,319 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network from Dec. 2, 2013 to Jan. 23, 2014. Early estimates from the report found that vaccination reduced the risk of illness by about 60% across all age groups.
Younger and middle-age adults are the least likely to be vaccinated, according to the report. Early estimates indicate that as of mid-November, just 34% of 18-64 year-olds had received this season’s influenza vaccine, compared with 41% of children aged 6 months to 17 years and 62% of adults aged 65 years or older.
Though vaccination should be the first line of defense, Dr. Frieden emphasized the importance of treating patients who present with flulike symptoms with antiviral medication immediately, rather than waiting on test results. This is especially important in patients with underlying medical conditions such as lung disease, asthma, diabetes, or obesity that increase their risk for complications, he said.
The most prevalent flu strain in the 2013-2014 season has been H1N1, which emerged as a pandemic in the United States in 2009. H1N1 has continued to circulate since the 2009-2010 season, but this is the first time it has returned as the dominant strain.
Because the predominant influenza strain can vary from season to season, CDC recommends annual flu shots for everyone aged 6 months or older, said Dr. Anne Schuchat, assistant surgeon general for the United States Public Health Service and director of the National Center for Immunization and Respiratory Diseases.
Dr. Schuchat said she hoped the greater access of the vaccine outside of medical offices would encourage more young adults to get the vaccine.
"Vaccinations are not just a doctor thing," she said. "They’re now available at workplaces, pharmacies, and grocery stores, which make it easier to get vaccinated."
She also added that the current flu season has not yet ended and could extend as far as May. "The season is not over," she said. "If you haven’t been vaccinated yet, it’s not too late to benefit."
Final results for flu vaccine effectiveness are expected to be released later this year.
So far, the 2013-2014 influenza season has been hardest on young and middle-age adults, with 61% of flu hospitalizations occurring in the 18- to 64-year-old age group, the Centers for Disease Control and Prevention reported in this week’s Morbidity and Mortality Weekly Report. This is a drastic jump from the previous season, when this age group accounted for only 35% of hospitalizations.
The report also found that the young adult population has accounted for an increased number of influenza-related deaths than in previous years, with adults aged 25-64 years of age accounting for 60% of flu deaths this season, compared with just 18%, 30%, and 47% for the previous three seasons, respectively (MMWR 2014; 63;137-42).
"Influenza can make anyone really sick, really fast, and it can kill," Dr. Thomas R. Frieden, director of the Centers for Disease Control and Prevention, said in a teleconference. "Vaccination is the single most important thing you can do to protect yourself."
The CDC conducted an interim analysis of flu vaccine effectiveness in 2,319 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network from Dec. 2, 2013 to Jan. 23, 2014. Early estimates from the report found that vaccination reduced the risk of illness by about 60% across all age groups.
Younger and middle-age adults are the least likely to be vaccinated, according to the report. Early estimates indicate that as of mid-November, just 34% of 18-64 year-olds had received this season’s influenza vaccine, compared with 41% of children aged 6 months to 17 years and 62% of adults aged 65 years or older.
Though vaccination should be the first line of defense, Dr. Frieden emphasized the importance of treating patients who present with flulike symptoms with antiviral medication immediately, rather than waiting on test results. This is especially important in patients with underlying medical conditions such as lung disease, asthma, diabetes, or obesity that increase their risk for complications, he said.
The most prevalent flu strain in the 2013-2014 season has been H1N1, which emerged as a pandemic in the United States in 2009. H1N1 has continued to circulate since the 2009-2010 season, but this is the first time it has returned as the dominant strain.
Because the predominant influenza strain can vary from season to season, CDC recommends annual flu shots for everyone aged 6 months or older, said Dr. Anne Schuchat, assistant surgeon general for the United States Public Health Service and director of the National Center for Immunization and Respiratory Diseases.
Dr. Schuchat said she hoped the greater access of the vaccine outside of medical offices would encourage more young adults to get the vaccine.
"Vaccinations are not just a doctor thing," she said. "They’re now available at workplaces, pharmacies, and grocery stores, which make it easier to get vaccinated."
She also added that the current flu season has not yet ended and could extend as far as May. "The season is not over," she said. "If you haven’t been vaccinated yet, it’s not too late to benefit."
Final results for flu vaccine effectiveness are expected to be released later this year.
So far, the 2013-2014 influenza season has been hardest on young and middle-age adults, with 61% of flu hospitalizations occurring in the 18- to 64-year-old age group, the Centers for Disease Control and Prevention reported in this week’s Morbidity and Mortality Weekly Report. This is a drastic jump from the previous season, when this age group accounted for only 35% of hospitalizations.
The report also found that the young adult population has accounted for an increased number of influenza-related deaths than in previous years, with adults aged 25-64 years of age accounting for 60% of flu deaths this season, compared with just 18%, 30%, and 47% for the previous three seasons, respectively (MMWR 2014; 63;137-42).
"Influenza can make anyone really sick, really fast, and it can kill," Dr. Thomas R. Frieden, director of the Centers for Disease Control and Prevention, said in a teleconference. "Vaccination is the single most important thing you can do to protect yourself."
The CDC conducted an interim analysis of flu vaccine effectiveness in 2,319 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network from Dec. 2, 2013 to Jan. 23, 2014. Early estimates from the report found that vaccination reduced the risk of illness by about 60% across all age groups.
Younger and middle-age adults are the least likely to be vaccinated, according to the report. Early estimates indicate that as of mid-November, just 34% of 18-64 year-olds had received this season’s influenza vaccine, compared with 41% of children aged 6 months to 17 years and 62% of adults aged 65 years or older.
Though vaccination should be the first line of defense, Dr. Frieden emphasized the importance of treating patients who present with flulike symptoms with antiviral medication immediately, rather than waiting on test results. This is especially important in patients with underlying medical conditions such as lung disease, asthma, diabetes, or obesity that increase their risk for complications, he said.
The most prevalent flu strain in the 2013-2014 season has been H1N1, which emerged as a pandemic in the United States in 2009. H1N1 has continued to circulate since the 2009-2010 season, but this is the first time it has returned as the dominant strain.
Because the predominant influenza strain can vary from season to season, CDC recommends annual flu shots for everyone aged 6 months or older, said Dr. Anne Schuchat, assistant surgeon general for the United States Public Health Service and director of the National Center for Immunization and Respiratory Diseases.
Dr. Schuchat said she hoped the greater access of the vaccine outside of medical offices would encourage more young adults to get the vaccine.
"Vaccinations are not just a doctor thing," she said. "They’re now available at workplaces, pharmacies, and grocery stores, which make it easier to get vaccinated."
She also added that the current flu season has not yet ended and could extend as far as May. "The season is not over," she said. "If you haven’t been vaccinated yet, it’s not too late to benefit."
Final results for flu vaccine effectiveness are expected to be released later this year.
FROM MORBIDITY AND MORTALITY WEEKLY REPORT
Major finding: Influenza vaccine reduced the risk of having to go to the doctor for flu-related illness by an estimated 61% across all ages.
Data source: An interim analysis of flu vaccine effectiveness in 2,319 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network from Dec. 2, 2013 to Jan. 23, 2014.
Disclosures: The authors did not report any disclosures.
Brain tractography finds white matter abnormalities in bipolar I patients
Whole brain tractography imaging shows decreased white matter integrity in patients with bipolar I disorder, compared with individuals without the disorder, a study published online in JAMA Psychiatry shows.
This effect was even more pronounced in bipolar patients with a history of psychotic features, defined as the patient having had at least one manic or depressive episode with delusions or hallucinations, wrote Samuel Sarrazin and his colleagues.
The investigators compared generalized fractional anisotropy (GFA) values in 118 bipolar I patients recruited from multiple university-affiliated centers in France, Germany, and the United States, with a control group of 86 participants who had no personal or family history of Axis I mood disorders, schizophrenia, or schizoaffective disorder. A lower GFA value suggests loss of integrity or coherence of white matter, the authors said.
At all of the sites, the Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale were administered, in addition to the Young Mania Rating Scale, and the National Adult Reading Test, reported Mr. Sarrazin, who is affiliated with several French medical institutions, including the Assistance Publique–Hôpitaux de Paris.
The mean age of disease onset among the patients with bipolar I was about 20.8 years, and the mean age at MRI was about 36.3 years. For the healthy controls, the mean age at MRI was 37.2 years (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4513]).
In a linear mixed-model analysis comparing the two groups, patients with bipolar I disorder had an average GFA value of 0.101 in the body of the corpus callosum, 0.113 in the splenium, and 0.079 in the anterior segment of the left hemisphere, compared with values of 0.102, 0.115, and 0.081, respectively, in the control group. Results remained significant when adjusting for false discovery rate (P = .03), and were consistent when researchers removed patients from the sample who had confounding factors such as elevated or mixed symptoms, the taking of lithium, and the existence of past alcohol abuse.
Bipolar I patients with a history of psychotic features had even lower GFA values than did bipolar patients with no psychotic history, with a mean GFA value of 0.100 in the body of the corpus callosum. This difference remained significant after adjusting for false discovery rate (P = .03).
"These results highlight the role of interhemispheric disconnectivity" in bipolar I disorder and suggest that bipolar I disorder with psychotic features "could be a relevant subtype of bipolar disorder with specific pathophysiological features," the investigators wrote. Additional large, multicenter studies are needed to compare bipolar I disorder with other psychotic disorders, and to further study such neuroimaging biomarkers, they added.
In an accompanying editorial, Dr. Kathryn R. Cullen and Dr. Kelvin O. Lim said that the latest findings advance the diffusion imaging literature in that the sample was large enough to address two important questions: "where [white matter] deficits are most consistent and how abnormalities vary across subtypes of [bipolar disorder]."
Furthermore, they said, the findings "conclusively affirm prior reports suggesting impaired [fractional anisotropy] in [white matter] tracts ... using state-of-the-art methods. Exciting contributions are the documentation of a more severe biological abnormality in the subgroup of patients with psychosis and additional evidence supporting an interhemispheric disconnectivity theory in [bipolar disorder]," wrote Dr. Cullen and Dr. Lim, both of the University of Minnesota, Minneapolis (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4638]).
Mr. Sarrazin and his colleagues cited several limitations to their study. First, they "did not explore the interrater and intersite reliability of the scales used in the study." Second, they did not include a "phantom procedure" to check the intercenter quality of the acquisitions. Third, the authors cannot exclude a possible effect of past medication use on the results. Fourth, given the large number of tracts to assess, the authors did not exploit other metrics from the orientation distribution function. Last, mean GFA values were calculated along each tract to perform comparisons, and localized decreases in GFA values might have gone undetected.
Neither Mr. Sarrazin nor his colleagues reported conflicts of interest. The study was funded by Alliance Nationale pour les Sciences de la Vie et de la Santé (aviesan), the Agence Nationale pour la Recherche, the Deutsche Forschungsgemeinschaft, the National Institute of Mental Health, and the Agence Régionale de Santé Ile-de-France.
Whole brain tractography imaging shows decreased white matter integrity in patients with bipolar I disorder, compared with individuals without the disorder, a study published online in JAMA Psychiatry shows.
This effect was even more pronounced in bipolar patients with a history of psychotic features, defined as the patient having had at least one manic or depressive episode with delusions or hallucinations, wrote Samuel Sarrazin and his colleagues.
The investigators compared generalized fractional anisotropy (GFA) values in 118 bipolar I patients recruited from multiple university-affiliated centers in France, Germany, and the United States, with a control group of 86 participants who had no personal or family history of Axis I mood disorders, schizophrenia, or schizoaffective disorder. A lower GFA value suggests loss of integrity or coherence of white matter, the authors said.
At all of the sites, the Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale were administered, in addition to the Young Mania Rating Scale, and the National Adult Reading Test, reported Mr. Sarrazin, who is affiliated with several French medical institutions, including the Assistance Publique–Hôpitaux de Paris.
The mean age of disease onset among the patients with bipolar I was about 20.8 years, and the mean age at MRI was about 36.3 years. For the healthy controls, the mean age at MRI was 37.2 years (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4513]).
In a linear mixed-model analysis comparing the two groups, patients with bipolar I disorder had an average GFA value of 0.101 in the body of the corpus callosum, 0.113 in the splenium, and 0.079 in the anterior segment of the left hemisphere, compared with values of 0.102, 0.115, and 0.081, respectively, in the control group. Results remained significant when adjusting for false discovery rate (P = .03), and were consistent when researchers removed patients from the sample who had confounding factors such as elevated or mixed symptoms, the taking of lithium, and the existence of past alcohol abuse.
Bipolar I patients with a history of psychotic features had even lower GFA values than did bipolar patients with no psychotic history, with a mean GFA value of 0.100 in the body of the corpus callosum. This difference remained significant after adjusting for false discovery rate (P = .03).
"These results highlight the role of interhemispheric disconnectivity" in bipolar I disorder and suggest that bipolar I disorder with psychotic features "could be a relevant subtype of bipolar disorder with specific pathophysiological features," the investigators wrote. Additional large, multicenter studies are needed to compare bipolar I disorder with other psychotic disorders, and to further study such neuroimaging biomarkers, they added.
In an accompanying editorial, Dr. Kathryn R. Cullen and Dr. Kelvin O. Lim said that the latest findings advance the diffusion imaging literature in that the sample was large enough to address two important questions: "where [white matter] deficits are most consistent and how abnormalities vary across subtypes of [bipolar disorder]."
Furthermore, they said, the findings "conclusively affirm prior reports suggesting impaired [fractional anisotropy] in [white matter] tracts ... using state-of-the-art methods. Exciting contributions are the documentation of a more severe biological abnormality in the subgroup of patients with psychosis and additional evidence supporting an interhemispheric disconnectivity theory in [bipolar disorder]," wrote Dr. Cullen and Dr. Lim, both of the University of Minnesota, Minneapolis (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4638]).
Mr. Sarrazin and his colleagues cited several limitations to their study. First, they "did not explore the interrater and intersite reliability of the scales used in the study." Second, they did not include a "phantom procedure" to check the intercenter quality of the acquisitions. Third, the authors cannot exclude a possible effect of past medication use on the results. Fourth, given the large number of tracts to assess, the authors did not exploit other metrics from the orientation distribution function. Last, mean GFA values were calculated along each tract to perform comparisons, and localized decreases in GFA values might have gone undetected.
Neither Mr. Sarrazin nor his colleagues reported conflicts of interest. The study was funded by Alliance Nationale pour les Sciences de la Vie et de la Santé (aviesan), the Agence Nationale pour la Recherche, the Deutsche Forschungsgemeinschaft, the National Institute of Mental Health, and the Agence Régionale de Santé Ile-de-France.
Whole brain tractography imaging shows decreased white matter integrity in patients with bipolar I disorder, compared with individuals without the disorder, a study published online in JAMA Psychiatry shows.
This effect was even more pronounced in bipolar patients with a history of psychotic features, defined as the patient having had at least one manic or depressive episode with delusions or hallucinations, wrote Samuel Sarrazin and his colleagues.
The investigators compared generalized fractional anisotropy (GFA) values in 118 bipolar I patients recruited from multiple university-affiliated centers in France, Germany, and the United States, with a control group of 86 participants who had no personal or family history of Axis I mood disorders, schizophrenia, or schizoaffective disorder. A lower GFA value suggests loss of integrity or coherence of white matter, the authors said.
At all of the sites, the Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale were administered, in addition to the Young Mania Rating Scale, and the National Adult Reading Test, reported Mr. Sarrazin, who is affiliated with several French medical institutions, including the Assistance Publique–Hôpitaux de Paris.
The mean age of disease onset among the patients with bipolar I was about 20.8 years, and the mean age at MRI was about 36.3 years. For the healthy controls, the mean age at MRI was 37.2 years (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4513]).
In a linear mixed-model analysis comparing the two groups, patients with bipolar I disorder had an average GFA value of 0.101 in the body of the corpus callosum, 0.113 in the splenium, and 0.079 in the anterior segment of the left hemisphere, compared with values of 0.102, 0.115, and 0.081, respectively, in the control group. Results remained significant when adjusting for false discovery rate (P = .03), and were consistent when researchers removed patients from the sample who had confounding factors such as elevated or mixed symptoms, the taking of lithium, and the existence of past alcohol abuse.
Bipolar I patients with a history of psychotic features had even lower GFA values than did bipolar patients with no psychotic history, with a mean GFA value of 0.100 in the body of the corpus callosum. This difference remained significant after adjusting for false discovery rate (P = .03).
"These results highlight the role of interhemispheric disconnectivity" in bipolar I disorder and suggest that bipolar I disorder with psychotic features "could be a relevant subtype of bipolar disorder with specific pathophysiological features," the investigators wrote. Additional large, multicenter studies are needed to compare bipolar I disorder with other psychotic disorders, and to further study such neuroimaging biomarkers, they added.
In an accompanying editorial, Dr. Kathryn R. Cullen and Dr. Kelvin O. Lim said that the latest findings advance the diffusion imaging literature in that the sample was large enough to address two important questions: "where [white matter] deficits are most consistent and how abnormalities vary across subtypes of [bipolar disorder]."
Furthermore, they said, the findings "conclusively affirm prior reports suggesting impaired [fractional anisotropy] in [white matter] tracts ... using state-of-the-art methods. Exciting contributions are the documentation of a more severe biological abnormality in the subgroup of patients with psychosis and additional evidence supporting an interhemispheric disconnectivity theory in [bipolar disorder]," wrote Dr. Cullen and Dr. Lim, both of the University of Minnesota, Minneapolis (JAMA Psychiatry 2014 Feb. 12 [doi:10.1001/jamapsychiatry.2013.4638]).
Mr. Sarrazin and his colleagues cited several limitations to their study. First, they "did not explore the interrater and intersite reliability of the scales used in the study." Second, they did not include a "phantom procedure" to check the intercenter quality of the acquisitions. Third, the authors cannot exclude a possible effect of past medication use on the results. Fourth, given the large number of tracts to assess, the authors did not exploit other metrics from the orientation distribution function. Last, mean GFA values were calculated along each tract to perform comparisons, and localized decreases in GFA values might have gone undetected.
Neither Mr. Sarrazin nor his colleagues reported conflicts of interest. The study was funded by Alliance Nationale pour les Sciences de la Vie et de la Santé (aviesan), the Agence Nationale pour la Recherche, the Deutsche Forschungsgemeinschaft, the National Institute of Mental Health, and the Agence Régionale de Santé Ile-de-France.
FROM JAMA PSYCHIATRY
Major finding: Patients with bipolar I disorder had lower generalized fractional anisotropy (GFA) values along the body and splenium of the corpus callosum than those in the control group, with a mean difference of –0.002.
Data source: An analysis using linear mixed models to compare mean GFA between 118 patients with bipolar and 86 controls.
Disclosures: Neither Mr. Sarrazin nor his colleagues reported conflicts of interest. The study was funded by Alliance nationale pour les Sciences de la Vie et de la Santé (aviesan), the Agence Nationale pour la Recherche, the Deutsche Forschungsgemeinschaft, the National Institute of Mental Health, and the Agence Régionale de Santé Ile-de-France.
FDA expands ibrutinib approval to include chronic lymphocytic leukemia
The Food and Drug Administration approved the use of ibrutinib (Imbruvica) for patients with chronic lymphocytic leukemia who have undergone at least one prior therapy, the agency announced Feb. 12.
The FDA’s expanded approval is based on a study of 48 CLL patients who had received previous therapy, the agency said in a statement. On average, participants were diagnosed 6.7 years before the study, and had received four therapies prior to ibrutinib. Patients received a 420-mg oral dose of the drug daily until either treatment reached unacceptable toxicity, or the disease progressed. The overall response rate was almost 58%, with duration of response ranging from 5.6 months to 24.2 months. An improvement in overall survival has not yet been demonstrated.
The drug was approved for CLL patients under the FDA’s accelerated approval process, which allows the agency to approve a medication "based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit," the FDA said.
In November 2013, the FDA approved ibrutinib under its accelerated process to treat patients with mantle cell lymphoma who had received previous therapy.
Drugs receiving accelerated approval are usually bound by an agreement with the company to conduct further confirmatory trials to demonstrate clinical benefit, the FDA said. Because of ibrutinib’s demonstrated potential to treat CLL, a rare disease, the drug received priority review and orphan-product designation.
The FDA reported a number of common side effects in the study, including thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever, constipation, peripheral edema, joint pain, nausea, mouth sores, sinus infection and dizziness.
Ibrutinib is manufactured by Pharmacyclics in Sunnyvale, Calif.
The Food and Drug Administration approved the use of ibrutinib (Imbruvica) for patients with chronic lymphocytic leukemia who have undergone at least one prior therapy, the agency announced Feb. 12.
The FDA’s expanded approval is based on a study of 48 CLL patients who had received previous therapy, the agency said in a statement. On average, participants were diagnosed 6.7 years before the study, and had received four therapies prior to ibrutinib. Patients received a 420-mg oral dose of the drug daily until either treatment reached unacceptable toxicity, or the disease progressed. The overall response rate was almost 58%, with duration of response ranging from 5.6 months to 24.2 months. An improvement in overall survival has not yet been demonstrated.
The drug was approved for CLL patients under the FDA’s accelerated approval process, which allows the agency to approve a medication "based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit," the FDA said.
In November 2013, the FDA approved ibrutinib under its accelerated process to treat patients with mantle cell lymphoma who had received previous therapy.
Drugs receiving accelerated approval are usually bound by an agreement with the company to conduct further confirmatory trials to demonstrate clinical benefit, the FDA said. Because of ibrutinib’s demonstrated potential to treat CLL, a rare disease, the drug received priority review and orphan-product designation.
The FDA reported a number of common side effects in the study, including thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever, constipation, peripheral edema, joint pain, nausea, mouth sores, sinus infection and dizziness.
Ibrutinib is manufactured by Pharmacyclics in Sunnyvale, Calif.
The Food and Drug Administration approved the use of ibrutinib (Imbruvica) for patients with chronic lymphocytic leukemia who have undergone at least one prior therapy, the agency announced Feb. 12.
The FDA’s expanded approval is based on a study of 48 CLL patients who had received previous therapy, the agency said in a statement. On average, participants were diagnosed 6.7 years before the study, and had received four therapies prior to ibrutinib. Patients received a 420-mg oral dose of the drug daily until either treatment reached unacceptable toxicity, or the disease progressed. The overall response rate was almost 58%, with duration of response ranging from 5.6 months to 24.2 months. An improvement in overall survival has not yet been demonstrated.
The drug was approved for CLL patients under the FDA’s accelerated approval process, which allows the agency to approve a medication "based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit," the FDA said.
In November 2013, the FDA approved ibrutinib under its accelerated process to treat patients with mantle cell lymphoma who had received previous therapy.
Drugs receiving accelerated approval are usually bound by an agreement with the company to conduct further confirmatory trials to demonstrate clinical benefit, the FDA said. Because of ibrutinib’s demonstrated potential to treat CLL, a rare disease, the drug received priority review and orphan-product designation.
The FDA reported a number of common side effects in the study, including thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever, constipation, peripheral edema, joint pain, nausea, mouth sores, sinus infection and dizziness.
Ibrutinib is manufactured by Pharmacyclics in Sunnyvale, Calif.
Beta-blockers linked to lower mortality in high-risk prostate cancer
The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.
Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.
The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.
Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.
Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).
Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.
The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."
The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.
The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.
Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.
The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.
Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.
Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).
Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.
The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."
The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.
The use of beta-blockers in men with metastatic and high-risk prostate cancer was associated with a reduced risk of prostate cancer–specific mortality independent of statin or acetylsalicylic acid use, according to a study published in European Urology.
Given these results, beta-blocker use should be further investigated where large registries are available, wrote Dr. Helene Hartvedt Grytli of the Institute of Cancer Research at Oslo University Hospital and her coinvestigators. "This is the first study to assess the association between beta-blocker use and prostate cancer–specific survival in a large cohort of men with known disease aggressiveness at diagnosis," they wrote.
The researchers obtained data from the Cancer Registry of Norway for men diagnosed with prostate cancer between 2004 and 2009. They coupled these data, using participants’ national identification numbers, with information from the Norwegian Prescription Database on filled prescriptions for beta-blockers, statins, and acetylsalicylic acid (ASA). Patients were considered users of these agents if they had filled at least one prescription of the respective drug both before and after diagnosis.
Mortality data were obtained from the Cancer Registry of Norway. A total of 3,561 men were eligible for analysis after exclusion criteria were accounted for; the criteria included having low- or intermediate-risk disease and planned treatment with either radical prostatectomy or radiation therapy.
Beta-blocker use was independently associated with a reduced risk of prostate cancer–specific mortality in a multivariable model (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001). The median follow-up time was 39 months (Eur. Urol. 2014;635-41).
Among beta-blocker users, 72% also used either ASA or statins. The investigators performed a survival analysis, adjusting for the use of these drugs to study any possible confounding effect. Statin use and ASA use were both associated with a reduction in prostate cancer–specific mortality when each drug was analyzed separately. Adjustment for the use of these drug classes did not substantially change the subhazard ratio for beta-blocker use.
The researchers did acknowledge a possible limitation of their study: "Unknown patient characteristics of this patient group might have confounded our results, and additional observation studies are warranted to establish whether beta-blocker use has an independent effect on prostate cancer progression and survival."
The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.
FROM EUROPEAN UROLOGY
Major finding: Beta-blocker use was associated with reduced prostate cancer mortality (adjusted subhazard ratio, 0.79; 95% confidence interval, 0.68-0.91; P = .001).
Data source: An analysis of 3,561 men with metastatic or high-risk prostate cancer, sampled from data obtained from the Cancer Registry of Norway and the Norwegian Prescription Database.
Disclosures: The study was funded by the South-Eastern Norway Regional Health Authority, Oslo University Hospital, and the University of Oslo.
CVS to discontinue sale of tobacco products
CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.
CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."
In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.
Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."
U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.
"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."
CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.
Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."
CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.
CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."
In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.
Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."
U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.
"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."
CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.
Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."
CVS Pharmacy will stop selling cigarettes and other tobacco products by October of this year, the company announced Feb. 5.
CVS President and Chief Executive Officer Larry Merlo said in a statement that the sale of tobacco products is contrary to CVS’s responsibility to help patients manage chronic diseases such as high blood pressure, high cholesterol, and diabetes. "All of these conditions are made worse by smoking," he said. "Tobacco products have no place in a setting where health care is delivered."
In addition to pulling cigarettes from its shelves, CVS also plans to launch a national smoking cessation program in the spring for those trying to quit, Mr. Merlo added.
Dr. Troyen A. Brennan, CVS executive vice president and chief medical officer, and Dr. Steven A. Schroeder, of the Smoking Cessation Leadership Center at the University of California, San Francisco, further explained the decision in a JAMA commentary (JAMA 2014 Feb. 5 [doi:10.1001/jama.2014.686]). "This action may not lead many people to stop smoking; smokers will probably simply go elsewhere to buy cigarettes," they wrote. "But if other retailers follow this lead, tobacco products will become much more difficult to obtain."
U.S. Department of Health and Human Services secretary Kathleen Sebelius praised the effort in a statement, calling the move an "unprecedented step in the retail industry" that would contribute to positive health effects for the next generation.
"Nearly 500,000 Americans die early each year due to smoking, and smoking costs us $289 billion annually," she said, citing the recently released 50th Anniversary Surgeon General Report on smoking and health. "If we fail to reverse course, 5.6 million American children alive today will die prematurely due to smoking."
CVS’s decision also drew support from the American Medical Association. AMA president Dr. Ardis Dee Hoven said in a statement that she applauds the company’s decision to put public health first and recognize the importance of "supporting health and wellness instead of contributing to disease and death caused by tobacco use." Dr. Hoven also said she hoped the change would inspire other pharmacies to follow suit by ending cigarette sales in stores.
Dr. W. Michael Alberts, chief medical officer at Moffitt Cancer Center in Tampa, also voiced approval. "This is a major decision by CVS," he said in an interview. "It may even be a watershed moment akin to the decision to ban smoking on airplanes. Let’s hope such decisions become commonplace in corporate boardrooms."
New teen drug abuse resources released
In advance of National Drug Facts Week, the National Institute on Drug Abuse has released a set of online resources to help parents identify and interact with teens who might be at risk of substance abuse and to provide information on treatment options. National Drug Facts Week is an annual week-long effort to educate teens about drug abuse and will take place from Jan. 27 to Feb. 2.
Adolescents’ substance use and treatment needs differ from those of adults, making it important to highlight available resources for teens and parents, NIDA said in a written statement. "Teens abuse different substances, experience different consequences, and are less likely to seek treatment on their own because they may not want or think they need help," according to the statement.
"Principles of Adolescent Substance Use Disorder Treatment: A Research-Based Guide" is a new online publication that describes approaches to drug abuse treatment, settings in which treatment may occur, and the role of loved ones and medical professionals in identifying substance abuse and assisting recovery.
NIDA will promote several additional resources during National Drug Facts Week to educate parents and teens about drug abuse. Visit National Drug Facts Week to learn more and to find community events and activities aimed at preventing and treating drug abuse in adolescents.
The National Institute on Drug Abuse is a division of the National Institutes of Health. For more information on NIDA research, visit the NIDA website.
In advance of National Drug Facts Week, the National Institute on Drug Abuse has released a set of online resources to help parents identify and interact with teens who might be at risk of substance abuse and to provide information on treatment options. National Drug Facts Week is an annual week-long effort to educate teens about drug abuse and will take place from Jan. 27 to Feb. 2.
Adolescents’ substance use and treatment needs differ from those of adults, making it important to highlight available resources for teens and parents, NIDA said in a written statement. "Teens abuse different substances, experience different consequences, and are less likely to seek treatment on their own because they may not want or think they need help," according to the statement.
"Principles of Adolescent Substance Use Disorder Treatment: A Research-Based Guide" is a new online publication that describes approaches to drug abuse treatment, settings in which treatment may occur, and the role of loved ones and medical professionals in identifying substance abuse and assisting recovery.
NIDA will promote several additional resources during National Drug Facts Week to educate parents and teens about drug abuse. Visit National Drug Facts Week to learn more and to find community events and activities aimed at preventing and treating drug abuse in adolescents.
The National Institute on Drug Abuse is a division of the National Institutes of Health. For more information on NIDA research, visit the NIDA website.
In advance of National Drug Facts Week, the National Institute on Drug Abuse has released a set of online resources to help parents identify and interact with teens who might be at risk of substance abuse and to provide information on treatment options. National Drug Facts Week is an annual week-long effort to educate teens about drug abuse and will take place from Jan. 27 to Feb. 2.
Adolescents’ substance use and treatment needs differ from those of adults, making it important to highlight available resources for teens and parents, NIDA said in a written statement. "Teens abuse different substances, experience different consequences, and are less likely to seek treatment on their own because they may not want or think they need help," according to the statement.
"Principles of Adolescent Substance Use Disorder Treatment: A Research-Based Guide" is a new online publication that describes approaches to drug abuse treatment, settings in which treatment may occur, and the role of loved ones and medical professionals in identifying substance abuse and assisting recovery.
NIDA will promote several additional resources during National Drug Facts Week to educate parents and teens about drug abuse. Visit National Drug Facts Week to learn more and to find community events and activities aimed at preventing and treating drug abuse in adolescents.
The National Institute on Drug Abuse is a division of the National Institutes of Health. For more information on NIDA research, visit the NIDA website.
FLINT trial halted early because of positive results
The phase II clinical trial of first-in-class farnesoid X receptor agonist obeticholic acid as a treatment for nonalcoholic steatohepatitis was stopped early because the trial endpoint was met with high significance, Intercept Pharmaceuticals announced Jan. 9.
The National Institute of Diabetes and Digestive and Kidney Diseases, which sponsored and conducted the FLINT trial, said in its statement that "OCA [obeticholic acid] has a significant beneficial effect on the liver damage due to NASH."
An interim analysis conducted by the Data Safety Monitoring Board of the trial found a highly statistically significant improvement in the primary endpoint, defined as "a decrease in the NAFLD Activity Score of at least two points with no worsening of fibrosis, as compared to placebo," the company said in a statement. The predetermined significance threshold for ending the trial was P less than .0031, but early results exceeded expectations with a significance of P = .0024.
An estimated 6 million adults in the United States have advanced liver fibrosis or cirrhosis caused bynonalcoholic steatohepatitis (NASH), said Dr. Mark Pruzanski, CEO of Intercept.
"This disease has seemingly come out of nowhere and has become an epidemic," he said. "On its current trajectory, NASH is expected to be the No. 1 indication for liver transplant over the next decade."
The FLINT trial, sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases, studied the efficacy of a 25-mg. oral dose of obeticholic acid (OCA) in approximately half of 283 biopsy-confirmed NASH patients over a period of 72 weeks. Patients were randomized to receive either a 25-mg dose of OCA or placebo for the treatment period.
Participants were 18 years of age or older, with histologic evidence of nonalcoholic steatohepatitis, based on a liver biopsy, obtained no more than 90 days prior to randomization and a NAFLD activity score of 4 or greater with at least one in each component of the NAFLD activity score (steatosis scored 0-3; ballooning degeneration scored 0-2; and lobular inflammation scored 0-3). End of study biopsies were conducted in patients after the 72-week treatment period.
As specified in the protocol, a 24-week follow-up period will start, and all FLINT participants will stop taking the drug or placebo no later than Jan. 20.
Lipid derangements involving elevated total [cholesterol] and LDL cholesterol and reduced HDL cholesterol have been seen in OCA, compared with placebo-treated patients. While lipid abnormalities are not uncommon in NASH, researchers will be checking to see if lipids return to pretreatment levels during this 24-week follow-up period.
During this period, both FLINT investigators and trial participants will remain blinded to treatment. The NIDDK expects to present the results of the trial in the fourth quarter of 2014.
OCA has not only been studied as a promising treatment for NASH. A 2013 study also found that OCA increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes and nonalcoholic fatty liver disease. Additionally, OCA is currently in a phase III trial for the treatment of primary biliary cirrhosis.
A concurrent trial to study OCA as a treatment for NASH is underway in Japan, added Dr. Pruzanski, with top-line results expected in 2015. Dr. Pruzanski said he hopes the trial’s unexpected success will help pave the path to FDA approval, pending final NIDDK analyses and publication of the results.
The FLINT trial was sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases.
Current data suggest that nonalcoholic fatty liver disease (NAFLD) is present in 30%-40% of adults in the United States, with a subset of this population having a more aggressive form of fatty liver called nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis. NASH is currently the third-leading cause for liver transplantation and is predicted to become the most common within 10-15 years (Gastroenterology 2011;141:1249-53).
Most NAFLD patients are overweight or obese and have underlying insulin resistance or diabetes mellitus. Comorbid illness is also common, with cardiovascular disease being the leading cause of death (Clin. Gastroenterol. Hepatol. 2012;10:837-58). Treatment for this condition is predicated on losing weight via diet and exercise, with 7%-10% weight loss being associated with improvement in underlying liver disease. Unfortunately, it is quite difficult for most patients to lose and maintain this weight level, so attention has turned to pharmacotherapy as a possible adjunct to diet and exercise. To date, pioglitazone and vitamin E have shown the most promise but are not universally effective, and they are linked to unwanted side effects or potential disease associations (Clin. Gastroenterol. Hepatol. 2012;10:837-58).
 |
| Dr. Stephen A. Harrison |
While these data are provocative, caution is needed until more complete data are presented. While the study met its primary endpoint, the report did not detail the source of the two-point improvement. NAS is based on an eight-point scale, with three points possible for the degree of steatosis, three points for lobular inflammation, and two points for ballooning degeneration of hepatocytes. Improvement in steatosis alone does not necessarily constitute improvement in NASH, the subset of disease that may progress in severity. It is important to know what percentage of patients actually resolved NASH or improved lobular inflammation or ballooning degeneration over placebo. Given that NASH patients are at increased risk for cardiovascular disease, it is concerning that serum cholesterol levels worsened. Details on LDL particle size and concentration as well as HDL subfractions are needed.
Additionally, further information on the tolerability and safety of OCA among NASH patients is eagerly awaited. While these preliminary data are promising, more details are needed before we can fully embrace this drug to treat NASH.
Dr. Stephen A. Harrison, COL, USA, MC, is director of medical education and associate dean, San Antonio Uniformed Services Health Education Consortium; chief of hepatology, Brooke Army Medical Center, San Antonio; professor of medicine, Uniformed Services University of the Health Sciences; and GI Consultant to the Office of the Surgeon General. He is an adviser to Genentech, Merck, and Nimbus Discovery, and has been on the speakers bureaus for Merck and Vertex within the past 12 months.
Current data suggest that nonalcoholic fatty liver disease (NAFLD) is present in 30%-40% of adults in the United States, with a subset of this population having a more aggressive form of fatty liver called nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis. NASH is currently the third-leading cause for liver transplantation and is predicted to become the most common within 10-15 years (Gastroenterology 2011;141:1249-53).
Most NAFLD patients are overweight or obese and have underlying insulin resistance or diabetes mellitus. Comorbid illness is also common, with cardiovascular disease being the leading cause of death (Clin. Gastroenterol. Hepatol. 2012;10:837-58). Treatment for this condition is predicated on losing weight via diet and exercise, with 7%-10% weight loss being associated with improvement in underlying liver disease. Unfortunately, it is quite difficult for most patients to lose and maintain this weight level, so attention has turned to pharmacotherapy as a possible adjunct to diet and exercise. To date, pioglitazone and vitamin E have shown the most promise but are not universally effective, and they are linked to unwanted side effects or potential disease associations (Clin. Gastroenterol. Hepatol. 2012;10:837-58).
|
| Dr. Stephen A. Harrison |
While these data are provocative, caution is needed until more complete data are presented. While the study met its primary endpoint, the report did not detail the source of the two-point improvement. NAS is based on an eight-point scale, with three points possible for the degree of steatosis, three points for lobular inflammation, and two points for ballooning degeneration of hepatocytes. Improvement in steatosis alone does not necessarily constitute improvement in NASH, the subset of disease that may progress in severity. It is important to know what percentage of patients actually resolved NASH or improved lobular inflammation or ballooning degeneration over placebo. Given that NASH patients are at increased risk for cardiovascular disease, it is concerning that serum cholesterol levels worsened. Details on LDL particle size and concentration as well as HDL subfractions are needed.
Additionally, further information on the tolerability and safety of OCA among NASH patients is eagerly awaited. While these preliminary data are promising, more details are needed before we can fully embrace this drug to treat NASH.
Dr. Stephen A. Harrison, COL, USA, MC, is director of medical education and associate dean, San Antonio Uniformed Services Health Education Consortium; chief of hepatology, Brooke Army Medical Center, San Antonio; professor of medicine, Uniformed Services University of the Health Sciences; and GI Consultant to the Office of the Surgeon General. He is an adviser to Genentech, Merck, and Nimbus Discovery, and has been on the speakers bureaus for Merck and Vertex within the past 12 months.
Current data suggest that nonalcoholic fatty liver disease (NAFLD) is present in 30%-40% of adults in the United States, with a subset of this population having a more aggressive form of fatty liver called nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis. NASH is currently the third-leading cause for liver transplantation and is predicted to become the most common within 10-15 years (Gastroenterology 2011;141:1249-53).
Most NAFLD patients are overweight or obese and have underlying insulin resistance or diabetes mellitus. Comorbid illness is also common, with cardiovascular disease being the leading cause of death (Clin. Gastroenterol. Hepatol. 2012;10:837-58). Treatment for this condition is predicated on losing weight via diet and exercise, with 7%-10% weight loss being associated with improvement in underlying liver disease. Unfortunately, it is quite difficult for most patients to lose and maintain this weight level, so attention has turned to pharmacotherapy as a possible adjunct to diet and exercise. To date, pioglitazone and vitamin E have shown the most promise but are not universally effective, and they are linked to unwanted side effects or potential disease associations (Clin. Gastroenterol. Hepatol. 2012;10:837-58).
|
| Dr. Stephen A. Harrison |
While these data are provocative, caution is needed until more complete data are presented. While the study met its primary endpoint, the report did not detail the source of the two-point improvement. NAS is based on an eight-point scale, with three points possible for the degree of steatosis, three points for lobular inflammation, and two points for ballooning degeneration of hepatocytes. Improvement in steatosis alone does not necessarily constitute improvement in NASH, the subset of disease that may progress in severity. It is important to know what percentage of patients actually resolved NASH or improved lobular inflammation or ballooning degeneration over placebo. Given that NASH patients are at increased risk for cardiovascular disease, it is concerning that serum cholesterol levels worsened. Details on LDL particle size and concentration as well as HDL subfractions are needed.
Additionally, further information on the tolerability and safety of OCA among NASH patients is eagerly awaited. While these preliminary data are promising, more details are needed before we can fully embrace this drug to treat NASH.
Dr. Stephen A. Harrison, COL, USA, MC, is director of medical education and associate dean, San Antonio Uniformed Services Health Education Consortium; chief of hepatology, Brooke Army Medical Center, San Antonio; professor of medicine, Uniformed Services University of the Health Sciences; and GI Consultant to the Office of the Surgeon General. He is an adviser to Genentech, Merck, and Nimbus Discovery, and has been on the speakers bureaus for Merck and Vertex within the past 12 months.
The phase II clinical trial of first-in-class farnesoid X receptor agonist obeticholic acid as a treatment for nonalcoholic steatohepatitis was stopped early because the trial endpoint was met with high significance, Intercept Pharmaceuticals announced Jan. 9.
The National Institute of Diabetes and Digestive and Kidney Diseases, which sponsored and conducted the FLINT trial, said in its statement that "OCA [obeticholic acid] has a significant beneficial effect on the liver damage due to NASH."
An interim analysis conducted by the Data Safety Monitoring Board of the trial found a highly statistically significant improvement in the primary endpoint, defined as "a decrease in the NAFLD Activity Score of at least two points with no worsening of fibrosis, as compared to placebo," the company said in a statement. The predetermined significance threshold for ending the trial was P less than .0031, but early results exceeded expectations with a significance of P = .0024.
An estimated 6 million adults in the United States have advanced liver fibrosis or cirrhosis caused bynonalcoholic steatohepatitis (NASH), said Dr. Mark Pruzanski, CEO of Intercept.
"This disease has seemingly come out of nowhere and has become an epidemic," he said. "On its current trajectory, NASH is expected to be the No. 1 indication for liver transplant over the next decade."
The FLINT trial, sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases, studied the efficacy of a 25-mg. oral dose of obeticholic acid (OCA) in approximately half of 283 biopsy-confirmed NASH patients over a period of 72 weeks. Patients were randomized to receive either a 25-mg dose of OCA or placebo for the treatment period.
Participants were 18 years of age or older, with histologic evidence of nonalcoholic steatohepatitis, based on a liver biopsy, obtained no more than 90 days prior to randomization and a NAFLD activity score of 4 or greater with at least one in each component of the NAFLD activity score (steatosis scored 0-3; ballooning degeneration scored 0-2; and lobular inflammation scored 0-3). End of study biopsies were conducted in patients after the 72-week treatment period.
As specified in the protocol, a 24-week follow-up period will start, and all FLINT participants will stop taking the drug or placebo no later than Jan. 20.
Lipid derangements involving elevated total [cholesterol] and LDL cholesterol and reduced HDL cholesterol have been seen in OCA, compared with placebo-treated patients. While lipid abnormalities are not uncommon in NASH, researchers will be checking to see if lipids return to pretreatment levels during this 24-week follow-up period.
During this period, both FLINT investigators and trial participants will remain blinded to treatment. The NIDDK expects to present the results of the trial in the fourth quarter of 2014.
OCA has not only been studied as a promising treatment for NASH. A 2013 study also found that OCA increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes and nonalcoholic fatty liver disease. Additionally, OCA is currently in a phase III trial for the treatment of primary biliary cirrhosis.
A concurrent trial to study OCA as a treatment for NASH is underway in Japan, added Dr. Pruzanski, with top-line results expected in 2015. Dr. Pruzanski said he hopes the trial’s unexpected success will help pave the path to FDA approval, pending final NIDDK analyses and publication of the results.
The FLINT trial was sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases.
The phase II clinical trial of first-in-class farnesoid X receptor agonist obeticholic acid as a treatment for nonalcoholic steatohepatitis was stopped early because the trial endpoint was met with high significance, Intercept Pharmaceuticals announced Jan. 9.
The National Institute of Diabetes and Digestive and Kidney Diseases, which sponsored and conducted the FLINT trial, said in its statement that "OCA [obeticholic acid] has a significant beneficial effect on the liver damage due to NASH."
An interim analysis conducted by the Data Safety Monitoring Board of the trial found a highly statistically significant improvement in the primary endpoint, defined as "a decrease in the NAFLD Activity Score of at least two points with no worsening of fibrosis, as compared to placebo," the company said in a statement. The predetermined significance threshold for ending the trial was P less than .0031, but early results exceeded expectations with a significance of P = .0024.
An estimated 6 million adults in the United States have advanced liver fibrosis or cirrhosis caused bynonalcoholic steatohepatitis (NASH), said Dr. Mark Pruzanski, CEO of Intercept.
"This disease has seemingly come out of nowhere and has become an epidemic," he said. "On its current trajectory, NASH is expected to be the No. 1 indication for liver transplant over the next decade."
The FLINT trial, sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases, studied the efficacy of a 25-mg. oral dose of obeticholic acid (OCA) in approximately half of 283 biopsy-confirmed NASH patients over a period of 72 weeks. Patients were randomized to receive either a 25-mg dose of OCA or placebo for the treatment period.
Participants were 18 years of age or older, with histologic evidence of nonalcoholic steatohepatitis, based on a liver biopsy, obtained no more than 90 days prior to randomization and a NAFLD activity score of 4 or greater with at least one in each component of the NAFLD activity score (steatosis scored 0-3; ballooning degeneration scored 0-2; and lobular inflammation scored 0-3). End of study biopsies were conducted in patients after the 72-week treatment period.
As specified in the protocol, a 24-week follow-up period will start, and all FLINT participants will stop taking the drug or placebo no later than Jan. 20.
Lipid derangements involving elevated total [cholesterol] and LDL cholesterol and reduced HDL cholesterol have been seen in OCA, compared with placebo-treated patients. While lipid abnormalities are not uncommon in NASH, researchers will be checking to see if lipids return to pretreatment levels during this 24-week follow-up period.
During this period, both FLINT investigators and trial participants will remain blinded to treatment. The NIDDK expects to present the results of the trial in the fourth quarter of 2014.
OCA has not only been studied as a promising treatment for NASH. A 2013 study also found that OCA increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type 2 diabetes and nonalcoholic fatty liver disease. Additionally, OCA is currently in a phase III trial for the treatment of primary biliary cirrhosis.
A concurrent trial to study OCA as a treatment for NASH is underway in Japan, added Dr. Pruzanski, with top-line results expected in 2015. Dr. Pruzanski said he hopes the trial’s unexpected success will help pave the path to FDA approval, pending final NIDDK analyses and publication of the results.
The FLINT trial was sponsored and conducted by the National Institute of Diabetes and Digestive and Kidney Diseases.
FROM A TELECONFERENCE HELD BY INTERCEPT PHARMACEUTICALS
Major finding: Treatment for nonalcoholic steatohepatitis with obeticholic acid resulted in a highly statistically significant improvement (P = .0024) for the primary endpoint.
Data source: A multicenter, double-blind, placebo-controlled clinical trial assessing the safety and efficacy of a 25-mg oral dose of first-in-class FXR-agonist OCA administered daily to biopsy-proven adult NASH patients over a 72-week treatment period.
Disclosures: The FLINT trial was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.