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First addiction medicine certification exam slated for fall 2017
The certification exam for the new subspecialty of addiction medicine will be held in fall 2017, the American Board of Preventive Medicine and the Addiction Medicine Foundation announced.
“We recognize the importance of providing certification in addiction medicine for physicians who have expertise and demonstrated knowledge in the prevention and treatment of substance use disorders,” ABPM President Marie Krousel-Wood, MD, said in a statement. “The advances in physician certification and training in addiction medicine set the stage to engage all of medicine as strong partners in addressing this critical public health issue.”
1) Have an appropriate medical degree or its equivalent.
2) Have current certification by at least one American Board of Medical Specialties member board.
3) Complete specified education and training or experience in the subspecialty field through either the Practice Pathway or an Accreditation Council for Graduate Medical Education–accredited fellowship training pathway.
4) Have a current, unrestricted, and valid license to practice medicine.
During the first 5 years the exam is administered, physicians will use the Practice Pathway to meet certification eligibility requirements. The includes a minimum of 1,920 hours engaged in the practice of addiction medicine occurring over at least 24 of the previous 60 months prior to the application, though the 24 months need not be continuous. Credit for completing a non-ACGME–accredited fellowship may be substituted for the time in practice requirements.
Dates and updates to the application process will be posted on ABPM’s website as they become available.
The American Society of Addiction Medicine announced a review course scheduled for July 27-29, 2017, in Dallas, to help prepare physicians for the certification exam.
The certification exam for the new subspecialty of addiction medicine will be held in fall 2017, the American Board of Preventive Medicine and the Addiction Medicine Foundation announced.
“We recognize the importance of providing certification in addiction medicine for physicians who have expertise and demonstrated knowledge in the prevention and treatment of substance use disorders,” ABPM President Marie Krousel-Wood, MD, said in a statement. “The advances in physician certification and training in addiction medicine set the stage to engage all of medicine as strong partners in addressing this critical public health issue.”
1) Have an appropriate medical degree or its equivalent.
2) Have current certification by at least one American Board of Medical Specialties member board.
3) Complete specified education and training or experience in the subspecialty field through either the Practice Pathway or an Accreditation Council for Graduate Medical Education–accredited fellowship training pathway.
4) Have a current, unrestricted, and valid license to practice medicine.
During the first 5 years the exam is administered, physicians will use the Practice Pathway to meet certification eligibility requirements. The includes a minimum of 1,920 hours engaged in the practice of addiction medicine occurring over at least 24 of the previous 60 months prior to the application, though the 24 months need not be continuous. Credit for completing a non-ACGME–accredited fellowship may be substituted for the time in practice requirements.
Dates and updates to the application process will be posted on ABPM’s website as they become available.
The American Society of Addiction Medicine announced a review course scheduled for July 27-29, 2017, in Dallas, to help prepare physicians for the certification exam.
The certification exam for the new subspecialty of addiction medicine will be held in fall 2017, the American Board of Preventive Medicine and the Addiction Medicine Foundation announced.
“We recognize the importance of providing certification in addiction medicine for physicians who have expertise and demonstrated knowledge in the prevention and treatment of substance use disorders,” ABPM President Marie Krousel-Wood, MD, said in a statement. “The advances in physician certification and training in addiction medicine set the stage to engage all of medicine as strong partners in addressing this critical public health issue.”
1) Have an appropriate medical degree or its equivalent.
2) Have current certification by at least one American Board of Medical Specialties member board.
3) Complete specified education and training or experience in the subspecialty field through either the Practice Pathway or an Accreditation Council for Graduate Medical Education–accredited fellowship training pathway.
4) Have a current, unrestricted, and valid license to practice medicine.
During the first 5 years the exam is administered, physicians will use the Practice Pathway to meet certification eligibility requirements. The includes a minimum of 1,920 hours engaged in the practice of addiction medicine occurring over at least 24 of the previous 60 months prior to the application, though the 24 months need not be continuous. Credit for completing a non-ACGME–accredited fellowship may be substituted for the time in practice requirements.
Dates and updates to the application process will be posted on ABPM’s website as they become available.
The American Society of Addiction Medicine announced a review course scheduled for July 27-29, 2017, in Dallas, to help prepare physicians for the certification exam.
Mild, moderate hypertriglyceridemia raises pancreatitis risk
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Mild to moderate hypertriglyceridemia is associated with increased risk of acute pancreatitis.
Major finding: Compared with normal triglyceride levels of less than 89 mg/dL, the risk for acute pancreatitis increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above.
Data source: A prospective, longitudinal cohort study involving 116,550 adults followed for 6.7 years.
Disclosures: This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Is better reporting to blame for the rise maternal mortality rates?
Better surveillance could be responsible for increased rates of U.S. maternal mortality, a sign that previous estimates were too low, according to a new study.
For more than 2 decades, rates of maternal deaths have increased significantly, climbing from 7.55 per 100,000 live births in 1993 to 9.88 in 1999, and rising again to 21.5 in 2014. This means the relative risk of maternal death between 2014 and 1993 was 2.84, while it was 2.17 between 2014 and 1999.
Although rising rates of obesity and other chronic conditions are often theorized as possible factors in the spiking maternal death rates K.S. Joseph, MD, PhD, of the University of British Columbia, Vancouver, and his colleagues suggest the more likely causes are improved maternal death surveillance and changes in how these deaths are coded.
This conclusion is based on a retrospective cohort analysis of maternal deaths and live births from 1993-2014 as recorded in the National Center for Health Statistics and the Wide-Ranging Online Data for Epidemiologic Research files of the Centers for Disease Control and Prevention (Obstet Gynecol 2017;129:91-100).
Surveillance and reporting changes have been implemented across the country over the last few decades. During the 1990s, some states began including a separate question regarding pregnancy on death certificates. Starting in 2003, pregnancy was added to the standardized checklist of causes of death on certificates used nationwide, although state-by-state implementation has varied. In addition, in 1999, ICD-10 codes for underlying causes of death were introduced, including O96 and O97 for late maternal deaths, O26.8 for specified pregnancy-related conditions, and O99 for other maternal diseases classifiable elsewhere.
When Dr. Joseph and his colleagues excluded from their analysis maternal deaths coded according to the new ICD-10 codes primarily related to renal disease and other maternal diseases classifiable elsewhere, the increase between 1999 and 2014 was erased, dropping the relative risk to 1.09 (95% CI, 0.94-1.27).
Adjustment for improvements in surveillance also wiped out the temporal increase in maternal mortality rates for a relative risk of 1.06 for 2013 compared to 1993 (95% CI, 0.90-1.25).
“Reports of temporal increases in maternal mortality rates in the United States have led to shock and soul-searching by clinicians,” the investigators wrote. “In fact, maternal deaths from conditions historically associated with high case fatality rates including preeclampsia, eclampsia, complications of labor and delivery, antepartum and postpartum hemorrhage, and abortion either declined substantially or remained stable between 1999 and 2014.”
The investigators did not report having any potential conflicts of interest.
[email protected]
On Twitter @whitneymcknight
Better surveillance could be responsible for increased rates of U.S. maternal mortality, a sign that previous estimates were too low, according to a new study.
For more than 2 decades, rates of maternal deaths have increased significantly, climbing from 7.55 per 100,000 live births in 1993 to 9.88 in 1999, and rising again to 21.5 in 2014. This means the relative risk of maternal death between 2014 and 1993 was 2.84, while it was 2.17 between 2014 and 1999.
Although rising rates of obesity and other chronic conditions are often theorized as possible factors in the spiking maternal death rates K.S. Joseph, MD, PhD, of the University of British Columbia, Vancouver, and his colleagues suggest the more likely causes are improved maternal death surveillance and changes in how these deaths are coded.
This conclusion is based on a retrospective cohort analysis of maternal deaths and live births from 1993-2014 as recorded in the National Center for Health Statistics and the Wide-Ranging Online Data for Epidemiologic Research files of the Centers for Disease Control and Prevention (Obstet Gynecol 2017;129:91-100).
Surveillance and reporting changes have been implemented across the country over the last few decades. During the 1990s, some states began including a separate question regarding pregnancy on death certificates. Starting in 2003, pregnancy was added to the standardized checklist of causes of death on certificates used nationwide, although state-by-state implementation has varied. In addition, in 1999, ICD-10 codes for underlying causes of death were introduced, including O96 and O97 for late maternal deaths, O26.8 for specified pregnancy-related conditions, and O99 for other maternal diseases classifiable elsewhere.
When Dr. Joseph and his colleagues excluded from their analysis maternal deaths coded according to the new ICD-10 codes primarily related to renal disease and other maternal diseases classifiable elsewhere, the increase between 1999 and 2014 was erased, dropping the relative risk to 1.09 (95% CI, 0.94-1.27).
Adjustment for improvements in surveillance also wiped out the temporal increase in maternal mortality rates for a relative risk of 1.06 for 2013 compared to 1993 (95% CI, 0.90-1.25).
“Reports of temporal increases in maternal mortality rates in the United States have led to shock and soul-searching by clinicians,” the investigators wrote. “In fact, maternal deaths from conditions historically associated with high case fatality rates including preeclampsia, eclampsia, complications of labor and delivery, antepartum and postpartum hemorrhage, and abortion either declined substantially or remained stable between 1999 and 2014.”
The investigators did not report having any potential conflicts of interest.
[email protected]
On Twitter @whitneymcknight
Better surveillance could be responsible for increased rates of U.S. maternal mortality, a sign that previous estimates were too low, according to a new study.
For more than 2 decades, rates of maternal deaths have increased significantly, climbing from 7.55 per 100,000 live births in 1993 to 9.88 in 1999, and rising again to 21.5 in 2014. This means the relative risk of maternal death between 2014 and 1993 was 2.84, while it was 2.17 between 2014 and 1999.
Although rising rates of obesity and other chronic conditions are often theorized as possible factors in the spiking maternal death rates K.S. Joseph, MD, PhD, of the University of British Columbia, Vancouver, and his colleagues suggest the more likely causes are improved maternal death surveillance and changes in how these deaths are coded.
This conclusion is based on a retrospective cohort analysis of maternal deaths and live births from 1993-2014 as recorded in the National Center for Health Statistics and the Wide-Ranging Online Data for Epidemiologic Research files of the Centers for Disease Control and Prevention (Obstet Gynecol 2017;129:91-100).
Surveillance and reporting changes have been implemented across the country over the last few decades. During the 1990s, some states began including a separate question regarding pregnancy on death certificates. Starting in 2003, pregnancy was added to the standardized checklist of causes of death on certificates used nationwide, although state-by-state implementation has varied. In addition, in 1999, ICD-10 codes for underlying causes of death were introduced, including O96 and O97 for late maternal deaths, O26.8 for specified pregnancy-related conditions, and O99 for other maternal diseases classifiable elsewhere.
When Dr. Joseph and his colleagues excluded from their analysis maternal deaths coded according to the new ICD-10 codes primarily related to renal disease and other maternal diseases classifiable elsewhere, the increase between 1999 and 2014 was erased, dropping the relative risk to 1.09 (95% CI, 0.94-1.27).
Adjustment for improvements in surveillance also wiped out the temporal increase in maternal mortality rates for a relative risk of 1.06 for 2013 compared to 1993 (95% CI, 0.90-1.25).
“Reports of temporal increases in maternal mortality rates in the United States have led to shock and soul-searching by clinicians,” the investigators wrote. “In fact, maternal deaths from conditions historically associated with high case fatality rates including preeclampsia, eclampsia, complications of labor and delivery, antepartum and postpartum hemorrhage, and abortion either declined substantially or remained stable between 1999 and 2014.”
The investigators did not report having any potential conflicts of interest.
[email protected]
On Twitter @whitneymcknight
Key clinical point:
Major finding: The relative risk for maternal death was 2.17 between 1999 and 2014, but dropped to 1.09 when certain new ICD-10 codes were excluded.
Data source: Retrospective cohort study of maternal deaths recorded in federal health data from 1993-2004.
Disclosures: The investigators did not report any potential conflicts of interest.
Delays in Diagnosis and Treatment of Infantile Spasms Are Common
HOUSTON—Children with infantile spasms commonly endure substantial delays in diagnosis and treatment, according to research presented at the 70th Annual Meeting of the American Epilepsy Society. “A simple lack of awareness of infantile spasms among healthcare providers may be responsible for potentially catastrophic delays in diagnosis and treatment,” said Shaun Hussain, MD, Director of the University of California, Los Angeles Infantile Spasms Program, and colleagues. “There is a desperate need for effective interventions to increase basic familiarity with infantile spasms among healthcare providers.” 
Treatment delay among children with infantile spasms is associated with poor long-term developmental outcomes. Dr. Hussain and his colleagues performed a study to measure delays in diagnosis and treatment of infantile spasms and identify barriers to optimal care.
The researchers retrospectively identified children with video-EEG-confirmed infantile spasms in a clinical database. When the children’s parents presented for follow-up, they were surveyed about their experiences with diagnosis and treatment. The investigators asked about medical and sociodemographic factors that could affect the care of infantile spasms. Specifically, the researchers determined the dates of infantile spasms onset, first visit with any healthcare provider, first visit with any neurologist, and first visit with an effective provider. Dr. Hussain and colleagues defined an effective provider as a healthcare provider who identified infantile spasms and prescribed a first-line treatment (ie, ACTH, corticosteroids, vigabatrin, or surgical resection). The investigators reviewed medical records to corroborate parents’ survey responses. They calculated the time to first effective provider using Cox proportional hazards regression.
The parents of 100 children with previous or ongoing infantile spasms were included in the study. Approximately 29% of patients were seen by an effective provider within one week of spasms onset. The median time from spasms onset to the first visit with an effective provider was 24.5 days. In sequential univariate analyses, parental sociodemographic attributes (eg, race, ethnicity, religion, household income, education level, type of healthcare insurance, and distance from patients’ home to the tertiary center) did not predict time to first effective provider. In open-ended discussions, numerous parents reported that their suspicions that “something was wrong” often had been discounted by pediatricians, emergency room physicians, and neurologists. In a qualitative analysis, many parents reported self-diagnosis using Internet resources and self-referral after various diagnostic difficulties and false reassurance by healthcare providers.
“A delay in diagnosis can lead to treatment failure and increase the risk of intellectual disability, autism, lifelong epilepsy, and even death,” said Dr. Hussain. “Some of these children can be cured, but successful treatment often depends on prompt diagnosis. The delays we observed are simply horrifying and represent a failure of our healthcare system to address a preventable cause of mental retardation.”
—Erik Greb
HOUSTON—Children with infantile spasms commonly endure substantial delays in diagnosis and treatment, according to research presented at the 70th Annual Meeting of the American Epilepsy Society. “A simple lack of awareness of infantile spasms among healthcare providers may be responsible for potentially catastrophic delays in diagnosis and treatment,” said Shaun Hussain, MD, Director of the University of California, Los Angeles Infantile Spasms Program, and colleagues. “There is a desperate need for effective interventions to increase basic familiarity with infantile spasms among healthcare providers.”
Treatment delay among children with infantile spasms is associated with poor long-term developmental outcomes. Dr. Hussain and his colleagues performed a study to measure delays in diagnosis and treatment of infantile spasms and identify barriers to optimal care.
The researchers retrospectively identified children with video-EEG-confirmed infantile spasms in a clinical database. When the children’s parents presented for follow-up, they were surveyed about their experiences with diagnosis and treatment. The investigators asked about medical and sociodemographic factors that could affect the care of infantile spasms. Specifically, the researchers determined the dates of infantile spasms onset, first visit with any healthcare provider, first visit with any neurologist, and first visit with an effective provider. Dr. Hussain and colleagues defined an effective provider as a healthcare provider who identified infantile spasms and prescribed a first-line treatment (ie, ACTH, corticosteroids, vigabatrin, or surgical resection). The investigators reviewed medical records to corroborate parents’ survey responses. They calculated the time to first effective provider using Cox proportional hazards regression.
The parents of 100 children with previous or ongoing infantile spasms were included in the study. Approximately 29% of patients were seen by an effective provider within one week of spasms onset. The median time from spasms onset to the first visit with an effective provider was 24.5 days. In sequential univariate analyses, parental sociodemographic attributes (eg, race, ethnicity, religion, household income, education level, type of healthcare insurance, and distance from patients’ home to the tertiary center) did not predict time to first effective provider. In open-ended discussions, numerous parents reported that their suspicions that “something was wrong” often had been discounted by pediatricians, emergency room physicians, and neurologists. In a qualitative analysis, many parents reported self-diagnosis using Internet resources and self-referral after various diagnostic difficulties and false reassurance by healthcare providers.
“A delay in diagnosis can lead to treatment failure and increase the risk of intellectual disability, autism, lifelong epilepsy, and even death,” said Dr. Hussain. “Some of these children can be cured, but successful treatment often depends on prompt diagnosis. The delays we observed are simply horrifying and represent a failure of our healthcare system to address a preventable cause of mental retardation.”
—Erik Greb
HOUSTON—Children with infantile spasms commonly endure substantial delays in diagnosis and treatment, according to research presented at the 70th Annual Meeting of the American Epilepsy Society. “A simple lack of awareness of infantile spasms among healthcare providers may be responsible for potentially catastrophic delays in diagnosis and treatment,” said Shaun Hussain, MD, Director of the University of California, Los Angeles Infantile Spasms Program, and colleagues. “There is a desperate need for effective interventions to increase basic familiarity with infantile spasms among healthcare providers.”
Treatment delay among children with infantile spasms is associated with poor long-term developmental outcomes. Dr. Hussain and his colleagues performed a study to measure delays in diagnosis and treatment of infantile spasms and identify barriers to optimal care.
The researchers retrospectively identified children with video-EEG-confirmed infantile spasms in a clinical database. When the children’s parents presented for follow-up, they were surveyed about their experiences with diagnosis and treatment. The investigators asked about medical and sociodemographic factors that could affect the care of infantile spasms. Specifically, the researchers determined the dates of infantile spasms onset, first visit with any healthcare provider, first visit with any neurologist, and first visit with an effective provider. Dr. Hussain and colleagues defined an effective provider as a healthcare provider who identified infantile spasms and prescribed a first-line treatment (ie, ACTH, corticosteroids, vigabatrin, or surgical resection). The investigators reviewed medical records to corroborate parents’ survey responses. They calculated the time to first effective provider using Cox proportional hazards regression.
The parents of 100 children with previous or ongoing infantile spasms were included in the study. Approximately 29% of patients were seen by an effective provider within one week of spasms onset. The median time from spasms onset to the first visit with an effective provider was 24.5 days. In sequential univariate analyses, parental sociodemographic attributes (eg, race, ethnicity, religion, household income, education level, type of healthcare insurance, and distance from patients’ home to the tertiary center) did not predict time to first effective provider. In open-ended discussions, numerous parents reported that their suspicions that “something was wrong” often had been discounted by pediatricians, emergency room physicians, and neurologists. In a qualitative analysis, many parents reported self-diagnosis using Internet resources and self-referral after various diagnostic difficulties and false reassurance by healthcare providers.
“A delay in diagnosis can lead to treatment failure and increase the risk of intellectual disability, autism, lifelong epilepsy, and even death,” said Dr. Hussain. “Some of these children can be cured, but successful treatment often depends on prompt diagnosis. The delays we observed are simply horrifying and represent a failure of our healthcare system to address a preventable cause of mental retardation.”
—Erik Greb
Sigma-1 agonist presses forward after positive results in small Alzheimer’s trial
SAN DIEGO – A novel Alzheimer’s disease drug candidate appeared to stabilize cognition and function over 57 weeks in a small, early-phase, open-label trial.
Patients with mild to moderate Alzheimer’s who took ANAVEX 2-73, an agonist of the sigma-1 receptor, experienced virtually no decline on either the Mini-Mental State Examination (MMSE) or the Alzheimer’s Disease Cooperative Study–activities of daily living (ADCS-ADL) functional scale. These findings correlated with significant improvements in the P300 evoked potential test – an electrophysiologic measure sometimes used to approximate synaptic connectivity and cortical processing speed.
The findings must be interpreted cautiously. The phase IIa study was designed to assess safety and tolerability; cognitive and functional endpoints were secondary. It comprised only 32 patients at baseline, 25 of whom completed both the 5-week, randomized, dose-finding, crossover trial and the 52-week, open-label, extension study. There was no placebo comparator. Instead, the study used three different sets of historical control data taken from other Alzheimer’s studies.
Nevertheless, the positive results are enough to propel ANAVEX 2-73 forward. The company will continue to treat and follow the extension study cohort, and plans to launch a placebo-controlled study in 2017, said Dr. Macfarlane, head of clinical governance for The Dementia Centre in Melbourne.
The 5-week, randomized, dose-finding, crossover trial started one group of patients on 30 or 50 mg/day oral ANAVEX 2-73 for 11 days after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 11 days of 3 mg/day or 5 mg/day intravenously. A second group first received 11 days of 3 mg/day or 5 mg/day ANAVEX 2-73 intravenously after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 30 or 50 mg/day oral ANAVEX 2-73 for 11 days. This was followed by a 52-week, open-label, extension trial of 10-50 mg/day orally, titrating each patient to the maximum tolerated dose. The extension phase was originally planned to last 6 months, but patients and caregivers wanted to continue on the medication, so the company extended it to 12 months. It is ongoing.
The sigma-1 receptor targeted by ANAVEX 2-73 is found on neurons and glia in many areas of the central nervous system. It modulates a number of processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke.
The sigma-1 receptor also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.
In preclinical testing, ANAVEX 2-73 showed an additional cognitive property, seeming to display a cognition-enhancing effect in both wild-type and AD model mice.
The mean age of the patients in the extension study was 71 years. The median MMSE score was 20.5. Most patients (78%) were taking a stable dose of acetylcholinesterase inhibitor. During the extension phase, they were titrated to the maximum tolerated dose; 14 mg was the minimum dose necessary to achieve a therapeutic effect and keep the MMSE stable, but Dr. Macfarlane didn’t discuss detailed dosing.
The primary endpoints were safety, tolerability, and pharmacokinetics. The exploratory measures included the P300 electroencephalogram, MMSE score, the Computerized Cogstate Alzheimer’s Battery, and the ADCS-ADL. The Hamilton Depression (HAM-D) Scale was also employed as a neuropsychiatric symptom measure.
The cohort had low baseline depression scores, with a mean score of 2 on the HAM-D. By study’s end, that had decreased to a mean of 1 point. The biggest change was seen in insomnia; all patients who endorsed it at baseline reported it gone by 12 weeks into treatment.
Patients also reported improvements in their ability to work or do other activities, in anxiety, agitation, hypochondriasis, and insight.
The P300 wave amplitude showed a small initial bump from about 6 to 7 microvolts by 4 weeks, and then a dip back down to about 6 microvolts until about week 32. Thereafter it steadily improved, landing at around 8 microvolts by 57 weeks – a level usually seen in healthy age-matched controls. There was a significant separation from the P300 decline seen in a matched historical Alzheimer’s cohort, which dropped to about 4 microvolts over a 52-week period while patients were taking donepezil.
The study employed a second historical control group in another cognitive assessment using the Computerized Cogstate Alzheimer’s Battery. All subjects in the large Australian prospective cohort study, called AIBL (Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing), were taking standard of care Alzheimer’s drugs. Compared with that cohort, the ANAVEX 2-73 group experienced benefits in processing speed, attention, and working memory, which became statistically significant at week 31 and continued to grow.
At 57 weeks, the mean MMSE score was stable, hovering around the baseline of 20. The ADCS-ADL declined slightly, from a mean of around 70 to around 65.
Finally, the investigators used yet another historical cohort as a comparator in a statistical analysis of projected cognitive and functional benefit. Compared with a pooled, placebo-arm, cohort study conducted by the Alzheimer Disease Cooperative Study Group over 12 months, ANAVEX 2-73 would have been associated with 1.8-point bump in score on the MMSE (P less than .016) and a 4-point benefit on the ADCS-ADL (P less than .019).
“The MMSE declined 45% less and the ADCS-ADL declined 56% less than what we would have expected from the historical control data,” Dr. Macfarlane said. “This is not only statistically significant, but clearly clinically meaningful for patients.”
Nearly all patients (98%) had some sort of adverse event, but most of them were mild transitory dizziness or headache; 76% of the events were grade 1, and 2% were grade 2. There were no serious adverse events. Three subjects dropped out because of adverse events (delirium, dizziness, and a combination of confusion, disorientation, and lethargy). There were no problematic interactions between the study drug and any standard of care AD medications.
Dr. Macfarlane has no financial interest in ANAVEX 2-73. He reported consultancies with Eli Lilly, Janssen-Cilag, and Lundbeck.
[email protected]
On Twitter @alz_gal
SAN DIEGO – A novel Alzheimer’s disease drug candidate appeared to stabilize cognition and function over 57 weeks in a small, early-phase, open-label trial.
Patients with mild to moderate Alzheimer’s who took ANAVEX 2-73, an agonist of the sigma-1 receptor, experienced virtually no decline on either the Mini-Mental State Examination (MMSE) or the Alzheimer’s Disease Cooperative Study–activities of daily living (ADCS-ADL) functional scale. These findings correlated with significant improvements in the P300 evoked potential test – an electrophysiologic measure sometimes used to approximate synaptic connectivity and cortical processing speed.
The findings must be interpreted cautiously. The phase IIa study was designed to assess safety and tolerability; cognitive and functional endpoints were secondary. It comprised only 32 patients at baseline, 25 of whom completed both the 5-week, randomized, dose-finding, crossover trial and the 52-week, open-label, extension study. There was no placebo comparator. Instead, the study used three different sets of historical control data taken from other Alzheimer’s studies.
Nevertheless, the positive results are enough to propel ANAVEX 2-73 forward. The company will continue to treat and follow the extension study cohort, and plans to launch a placebo-controlled study in 2017, said Dr. Macfarlane, head of clinical governance for The Dementia Centre in Melbourne.
The 5-week, randomized, dose-finding, crossover trial started one group of patients on 30 or 50 mg/day oral ANAVEX 2-73 for 11 days after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 11 days of 3 mg/day or 5 mg/day intravenously. A second group first received 11 days of 3 mg/day or 5 mg/day ANAVEX 2-73 intravenously after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 30 or 50 mg/day oral ANAVEX 2-73 for 11 days. This was followed by a 52-week, open-label, extension trial of 10-50 mg/day orally, titrating each patient to the maximum tolerated dose. The extension phase was originally planned to last 6 months, but patients and caregivers wanted to continue on the medication, so the company extended it to 12 months. It is ongoing.
The sigma-1 receptor targeted by ANAVEX 2-73 is found on neurons and glia in many areas of the central nervous system. It modulates a number of processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke.
The sigma-1 receptor also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.
In preclinical testing, ANAVEX 2-73 showed an additional cognitive property, seeming to display a cognition-enhancing effect in both wild-type and AD model mice.
The mean age of the patients in the extension study was 71 years. The median MMSE score was 20.5. Most patients (78%) were taking a stable dose of acetylcholinesterase inhibitor. During the extension phase, they were titrated to the maximum tolerated dose; 14 mg was the minimum dose necessary to achieve a therapeutic effect and keep the MMSE stable, but Dr. Macfarlane didn’t discuss detailed dosing.
The primary endpoints were safety, tolerability, and pharmacokinetics. The exploratory measures included the P300 electroencephalogram, MMSE score, the Computerized Cogstate Alzheimer’s Battery, and the ADCS-ADL. The Hamilton Depression (HAM-D) Scale was also employed as a neuropsychiatric symptom measure.
The cohort had low baseline depression scores, with a mean score of 2 on the HAM-D. By study’s end, that had decreased to a mean of 1 point. The biggest change was seen in insomnia; all patients who endorsed it at baseline reported it gone by 12 weeks into treatment.
Patients also reported improvements in their ability to work or do other activities, in anxiety, agitation, hypochondriasis, and insight.
The P300 wave amplitude showed a small initial bump from about 6 to 7 microvolts by 4 weeks, and then a dip back down to about 6 microvolts until about week 32. Thereafter it steadily improved, landing at around 8 microvolts by 57 weeks – a level usually seen in healthy age-matched controls. There was a significant separation from the P300 decline seen in a matched historical Alzheimer’s cohort, which dropped to about 4 microvolts over a 52-week period while patients were taking donepezil.
The study employed a second historical control group in another cognitive assessment using the Computerized Cogstate Alzheimer’s Battery. All subjects in the large Australian prospective cohort study, called AIBL (Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing), were taking standard of care Alzheimer’s drugs. Compared with that cohort, the ANAVEX 2-73 group experienced benefits in processing speed, attention, and working memory, which became statistically significant at week 31 and continued to grow.
At 57 weeks, the mean MMSE score was stable, hovering around the baseline of 20. The ADCS-ADL declined slightly, from a mean of around 70 to around 65.
Finally, the investigators used yet another historical cohort as a comparator in a statistical analysis of projected cognitive and functional benefit. Compared with a pooled, placebo-arm, cohort study conducted by the Alzheimer Disease Cooperative Study Group over 12 months, ANAVEX 2-73 would have been associated with 1.8-point bump in score on the MMSE (P less than .016) and a 4-point benefit on the ADCS-ADL (P less than .019).
“The MMSE declined 45% less and the ADCS-ADL declined 56% less than what we would have expected from the historical control data,” Dr. Macfarlane said. “This is not only statistically significant, but clearly clinically meaningful for patients.”
Nearly all patients (98%) had some sort of adverse event, but most of them were mild transitory dizziness or headache; 76% of the events were grade 1, and 2% were grade 2. There were no serious adverse events. Three subjects dropped out because of adverse events (delirium, dizziness, and a combination of confusion, disorientation, and lethargy). There were no problematic interactions between the study drug and any standard of care AD medications.
Dr. Macfarlane has no financial interest in ANAVEX 2-73. He reported consultancies with Eli Lilly, Janssen-Cilag, and Lundbeck.
[email protected]
On Twitter @alz_gal
SAN DIEGO – A novel Alzheimer’s disease drug candidate appeared to stabilize cognition and function over 57 weeks in a small, early-phase, open-label trial.
Patients with mild to moderate Alzheimer’s who took ANAVEX 2-73, an agonist of the sigma-1 receptor, experienced virtually no decline on either the Mini-Mental State Examination (MMSE) or the Alzheimer’s Disease Cooperative Study–activities of daily living (ADCS-ADL) functional scale. These findings correlated with significant improvements in the P300 evoked potential test – an electrophysiologic measure sometimes used to approximate synaptic connectivity and cortical processing speed.
The findings must be interpreted cautiously. The phase IIa study was designed to assess safety and tolerability; cognitive and functional endpoints were secondary. It comprised only 32 patients at baseline, 25 of whom completed both the 5-week, randomized, dose-finding, crossover trial and the 52-week, open-label, extension study. There was no placebo comparator. Instead, the study used three different sets of historical control data taken from other Alzheimer’s studies.
Nevertheless, the positive results are enough to propel ANAVEX 2-73 forward. The company will continue to treat and follow the extension study cohort, and plans to launch a placebo-controlled study in 2017, said Dr. Macfarlane, head of clinical governance for The Dementia Centre in Melbourne.
The 5-week, randomized, dose-finding, crossover trial started one group of patients on 30 or 50 mg/day oral ANAVEX 2-73 for 11 days after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 11 days of 3 mg/day or 5 mg/day intravenously. A second group first received 11 days of 3 mg/day or 5 mg/day ANAVEX 2-73 intravenously after an initial 2-day, single-dose, pharmacokinetic analysis, followed by an 11-day washout period, and then 30 or 50 mg/day oral ANAVEX 2-73 for 11 days. This was followed by a 52-week, open-label, extension trial of 10-50 mg/day orally, titrating each patient to the maximum tolerated dose. The extension phase was originally planned to last 6 months, but patients and caregivers wanted to continue on the medication, so the company extended it to 12 months. It is ongoing.
The sigma-1 receptor targeted by ANAVEX 2-73 is found on neurons and glia in many areas of the central nervous system. It modulates a number of processes implicated in neurodegenerative diseases, including glutamate and calcium activity, reaction to oxidative stress, and mitochondrial function. There is some evidence that sigma-1 receptor activation can induce neuronal regrowth and functional recovery after stroke.
The sigma-1 receptor also appears to play a role in helping cells clear misfolded proteins – a pathway that makes it an attractive drug target in Alzheimer’s disease, as well as other neurodegenerative diseases with aberrant proteins, such as Parkinson’s and Huntington’s diseases.
In preclinical testing, ANAVEX 2-73 showed an additional cognitive property, seeming to display a cognition-enhancing effect in both wild-type and AD model mice.
The mean age of the patients in the extension study was 71 years. The median MMSE score was 20.5. Most patients (78%) were taking a stable dose of acetylcholinesterase inhibitor. During the extension phase, they were titrated to the maximum tolerated dose; 14 mg was the minimum dose necessary to achieve a therapeutic effect and keep the MMSE stable, but Dr. Macfarlane didn’t discuss detailed dosing.
The primary endpoints were safety, tolerability, and pharmacokinetics. The exploratory measures included the P300 electroencephalogram, MMSE score, the Computerized Cogstate Alzheimer’s Battery, and the ADCS-ADL. The Hamilton Depression (HAM-D) Scale was also employed as a neuropsychiatric symptom measure.
The cohort had low baseline depression scores, with a mean score of 2 on the HAM-D. By study’s end, that had decreased to a mean of 1 point. The biggest change was seen in insomnia; all patients who endorsed it at baseline reported it gone by 12 weeks into treatment.
Patients also reported improvements in their ability to work or do other activities, in anxiety, agitation, hypochondriasis, and insight.
The P300 wave amplitude showed a small initial bump from about 6 to 7 microvolts by 4 weeks, and then a dip back down to about 6 microvolts until about week 32. Thereafter it steadily improved, landing at around 8 microvolts by 57 weeks – a level usually seen in healthy age-matched controls. There was a significant separation from the P300 decline seen in a matched historical Alzheimer’s cohort, which dropped to about 4 microvolts over a 52-week period while patients were taking donepezil.
The study employed a second historical control group in another cognitive assessment using the Computerized Cogstate Alzheimer’s Battery. All subjects in the large Australian prospective cohort study, called AIBL (Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing), were taking standard of care Alzheimer’s drugs. Compared with that cohort, the ANAVEX 2-73 group experienced benefits in processing speed, attention, and working memory, which became statistically significant at week 31 and continued to grow.
At 57 weeks, the mean MMSE score was stable, hovering around the baseline of 20. The ADCS-ADL declined slightly, from a mean of around 70 to around 65.
Finally, the investigators used yet another historical cohort as a comparator in a statistical analysis of projected cognitive and functional benefit. Compared with a pooled, placebo-arm, cohort study conducted by the Alzheimer Disease Cooperative Study Group over 12 months, ANAVEX 2-73 would have been associated with 1.8-point bump in score on the MMSE (P less than .016) and a 4-point benefit on the ADCS-ADL (P less than .019).
“The MMSE declined 45% less and the ADCS-ADL declined 56% less than what we would have expected from the historical control data,” Dr. Macfarlane said. “This is not only statistically significant, but clearly clinically meaningful for patients.”
Nearly all patients (98%) had some sort of adverse event, but most of them were mild transitory dizziness or headache; 76% of the events were grade 1, and 2% were grade 2. There were no serious adverse events. Three subjects dropped out because of adverse events (delirium, dizziness, and a combination of confusion, disorientation, and lethargy). There were no problematic interactions between the study drug and any standard of care AD medications.
Dr. Macfarlane has no financial interest in ANAVEX 2-73. He reported consultancies with Eli Lilly, Janssen-Cilag, and Lundbeck.
[email protected]
On Twitter @alz_gal
AT CTAD
Key clinical point:
Major finding: At 57 weeks, the mean MMSE score stayed around the baseline of 20. The ADCS-ADL declined slightly, from about 70 to 65.
Data source: A phase IIa study comprising 32 patients, 25 of whom completed 57 weeks of treatment.
Disclosures: Dr. Macfarlane has no financial ties with Anavex Life Sciences, which is developing the drug. He reported consultancies with Eli Lilly, Janssen-Cilag, and Lundbeck.
Macrolide monotherapy works in some NTM lung disease
Patients with cystic fibrosis or bronchiectasis and one form of Mycobacterium abscessus disease can be successfully treated with long-term oral macrolide monotherapy following short-term intravenous combination antibiotic therapy, a Korean research team has shown.
The M. abscessus complex is implicated in between a fifth and half of all cases of lung disease caused by nontuberculous mycobacteria (NTM). Though treatment is notoriously difficult and prolonged in all NTM lung disease, one subspecies of M. abscessus – M. massiliense – lacks the active gene needed for developing resistance to macrolide-based antibiotics, making it potentially more readily treated.
In research published in CHEST, Won-Jung Koh, MD, of Samsung Medical Center and Sungkyunkwan University in Seoul, South Korea, and colleagues, sought to determine the optimal treatment protocol for patients with massiliense disease (Chest. 2016 Dec;150[6]:1211-21). They identified 71 patients with massiliense disease who had initiated antibiotic treatment between January 2007 and December 2012. These patients were part of an ongoing prospective cohort study on NTM lung disease. The first 28 patients in the study were hospitalized for 4 weeks and treated with intravenous amikacin and cefoxitin along with oral clarithromycin and a fluoroquinolone. Following discharge these patients remained on the oral agents for 24 months.
Two years into the study, the protocol changed, and the next 43 patients were treated with a 2-week course of intravenous amikacin and cefoxitin along with the oral agents. In some patients, azithromycin, which came into use in Korea for NTM lung disease in 2011, replaced a fluoroquinolone. After discharge, all patients stayed on the oral macrolides (with seven also taking a fluoroquinolone) until their sputum cultures were negative for 12 months.
For the patients treated for 4 weeks, the response rates after 12 months of treatment were 89% for symptoms, 79% for computed tomography, and 100% for negative sputum cultures. In the patients treated for 2 weeks, they were 100%, 91%, and 91%, respectively. None of these differences between the two groups were statistically significant. Median total treatment duration, however, was significantly shorter – by nearly a year – in the 2-week plus macrolide monotherapy group than in the other group of patients (15.2 months vs. 23.9 months, P less than .001).
Acquired macrolide resistance developed in two patients in the group who received a 2-week course of intravenous amikacin and cefoxitin along with the oral agents, including one case of high-level clarithromycin resistance. Genotyping revealed reinfection with different strains of M. massiliense.
“[Oral] macrolide therapy after an initial 2-week course of combination antibiotics, rather than long-term parenteral antibiotics, might be effective in most patients with M. massiliense lung disease,” Dr. Koh and colleagues wrote, noting that their study’s nonrandomized single-site design was a limitation, and that multicenter randomized trials would be needed “to assess the efficacy” of the findings.
The Korean government funded Dr. Koh and colleagues’ study. None of the authors disclosed conflicts of interest.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
Patients with cystic fibrosis or bronchiectasis and one form of Mycobacterium abscessus disease can be successfully treated with long-term oral macrolide monotherapy following short-term intravenous combination antibiotic therapy, a Korean research team has shown.
The M. abscessus complex is implicated in between a fifth and half of all cases of lung disease caused by nontuberculous mycobacteria (NTM). Though treatment is notoriously difficult and prolonged in all NTM lung disease, one subspecies of M. abscessus – M. massiliense – lacks the active gene needed for developing resistance to macrolide-based antibiotics, making it potentially more readily treated.
In research published in CHEST, Won-Jung Koh, MD, of Samsung Medical Center and Sungkyunkwan University in Seoul, South Korea, and colleagues, sought to determine the optimal treatment protocol for patients with massiliense disease (Chest. 2016 Dec;150[6]:1211-21). They identified 71 patients with massiliense disease who had initiated antibiotic treatment between January 2007 and December 2012. These patients were part of an ongoing prospective cohort study on NTM lung disease. The first 28 patients in the study were hospitalized for 4 weeks and treated with intravenous amikacin and cefoxitin along with oral clarithromycin and a fluoroquinolone. Following discharge these patients remained on the oral agents for 24 months.
Two years into the study, the protocol changed, and the next 43 patients were treated with a 2-week course of intravenous amikacin and cefoxitin along with the oral agents. In some patients, azithromycin, which came into use in Korea for NTM lung disease in 2011, replaced a fluoroquinolone. After discharge, all patients stayed on the oral macrolides (with seven also taking a fluoroquinolone) until their sputum cultures were negative for 12 months.
For the patients treated for 4 weeks, the response rates after 12 months of treatment were 89% for symptoms, 79% for computed tomography, and 100% for negative sputum cultures. In the patients treated for 2 weeks, they were 100%, 91%, and 91%, respectively. None of these differences between the two groups were statistically significant. Median total treatment duration, however, was significantly shorter – by nearly a year – in the 2-week plus macrolide monotherapy group than in the other group of patients (15.2 months vs. 23.9 months, P less than .001).
Acquired macrolide resistance developed in two patients in the group who received a 2-week course of intravenous amikacin and cefoxitin along with the oral agents, including one case of high-level clarithromycin resistance. Genotyping revealed reinfection with different strains of M. massiliense.
“[Oral] macrolide therapy after an initial 2-week course of combination antibiotics, rather than long-term parenteral antibiotics, might be effective in most patients with M. massiliense lung disease,” Dr. Koh and colleagues wrote, noting that their study’s nonrandomized single-site design was a limitation, and that multicenter randomized trials would be needed “to assess the efficacy” of the findings.
The Korean government funded Dr. Koh and colleagues’ study. None of the authors disclosed conflicts of interest.
Patients with cystic fibrosis or bronchiectasis and one form of Mycobacterium abscessus disease can be successfully treated with long-term oral macrolide monotherapy following short-term intravenous combination antibiotic therapy, a Korean research team has shown.
The M. abscessus complex is implicated in between a fifth and half of all cases of lung disease caused by nontuberculous mycobacteria (NTM). Though treatment is notoriously difficult and prolonged in all NTM lung disease, one subspecies of M. abscessus – M. massiliense – lacks the active gene needed for developing resistance to macrolide-based antibiotics, making it potentially more readily treated.
In research published in CHEST, Won-Jung Koh, MD, of Samsung Medical Center and Sungkyunkwan University in Seoul, South Korea, and colleagues, sought to determine the optimal treatment protocol for patients with massiliense disease (Chest. 2016 Dec;150[6]:1211-21). They identified 71 patients with massiliense disease who had initiated antibiotic treatment between January 2007 and December 2012. These patients were part of an ongoing prospective cohort study on NTM lung disease. The first 28 patients in the study were hospitalized for 4 weeks and treated with intravenous amikacin and cefoxitin along with oral clarithromycin and a fluoroquinolone. Following discharge these patients remained on the oral agents for 24 months.
Two years into the study, the protocol changed, and the next 43 patients were treated with a 2-week course of intravenous amikacin and cefoxitin along with the oral agents. In some patients, azithromycin, which came into use in Korea for NTM lung disease in 2011, replaced a fluoroquinolone. After discharge, all patients stayed on the oral macrolides (with seven also taking a fluoroquinolone) until their sputum cultures were negative for 12 months.
For the patients treated for 4 weeks, the response rates after 12 months of treatment were 89% for symptoms, 79% for computed tomography, and 100% for negative sputum cultures. In the patients treated for 2 weeks, they were 100%, 91%, and 91%, respectively. None of these differences between the two groups were statistically significant. Median total treatment duration, however, was significantly shorter – by nearly a year – in the 2-week plus macrolide monotherapy group than in the other group of patients (15.2 months vs. 23.9 months, P less than .001).
Acquired macrolide resistance developed in two patients in the group who received a 2-week course of intravenous amikacin and cefoxitin along with the oral agents, including one case of high-level clarithromycin resistance. Genotyping revealed reinfection with different strains of M. massiliense.
“[Oral] macrolide therapy after an initial 2-week course of combination antibiotics, rather than long-term parenteral antibiotics, might be effective in most patients with M. massiliense lung disease,” Dr. Koh and colleagues wrote, noting that their study’s nonrandomized single-site design was a limitation, and that multicenter randomized trials would be needed “to assess the efficacy” of the findings.
The Korean government funded Dr. Koh and colleagues’ study. None of the authors disclosed conflicts of interest.
FROM CHEST
Key clinical point: A short course of intravenous antibiotics followed by oral macrolides may be effective at treating lung disease caused by the massiliense subspecies of M. abscessus.
Major finding: Of 43 patients receiving 2 weeks of combination antibiotics followed by a year of oral macrolides, 39 (91%) converted to negative sputum cultures before 12 months.
Data source: A prospective cohort study enrolling 71 patients at a single treatment center in Korea.
Disclosures: The Korean government sponsored the study and investigators disclosed no conflicts of interest.
XR version of Synjardy gets FDA’s nod
for use in the management of blood sugar in adults with type 2 diabetes. The drug, to be marketed as Synjardy XR by Boehringer Ingelheim and Eli Lilly, is intended for use with a diet and exercise program.
Its standard release formulation was approved in August 2015.
FDA approved the extended-release version on Dec. 12. The updated label includes a boxed warning regarding the risk of metformin-associated lactic acidosis
Empagliflozin recently received an FDA indication as a medication for use in reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease, the first drug for type 2 diabetes to do so.
The label includes information of the drug’s four doses, all of which contain 1,000 mg of metformin plus empagliflozin in strengths of 5 mg, 10 mg, 12.5 mg, and 25 mg.
Among patients who are already taking metformin and plan to begin a regimen of Synjardy XR, their best choice is to switch to the formulation containing a similar daily dose of metformin and a total daily dose of 10 mg empagliflozin. Those already on empagliflozin should switch to Synjardy XR containing the same daily dose of empagliflozin and a total daily dose of 1,000 mg metformin. Dosing may be adjusted upward on the basis of effectiveness and tolerability up to a maximum of 25 mg empagliflozin/2,000 mg metformin, taken once daily with a meal in the morning.
Synjardy XR is contraindicated in patients with an estimated glomerular filtration rate of less than 45 mL/min per 1.73 m2. Renal function should be assessed in patients with impaired renal function before taking Synjardy XR.
Several clinical trials tested coadministration of metformin and empagliflozin. In the largest, 637 patients with type 2 diabetes who were inadequately controlled (hemoglobin A1c of 7%-10%) with 1,500 mg metformin were randomized to receive placebo, 10 mg empagliflozin, or 25 mg empagliflozin for 24 weeks. Both the 10-mg and 25-mg dosages of empagliflozin resulted in significant reductions compared with placebo in HbA1c (–0.7% and –0.8%, respectively) fasting glucose (–26 mg/dL and –29 mg/dL), and body weight (–2 kg and –2.5 kg).
The single-pill formulation of Synjardy XR was not tested in clinical trials for efficacy; however, several trials performed in healthy subjects showed bioequivalence of the fixed dose combination, compared with separate pills.
[email protected]
for use in the management of blood sugar in adults with type 2 diabetes. The drug, to be marketed as Synjardy XR by Boehringer Ingelheim and Eli Lilly, is intended for use with a diet and exercise program.
Its standard release formulation was approved in August 2015.
FDA approved the extended-release version on Dec. 12. The updated label includes a boxed warning regarding the risk of metformin-associated lactic acidosis
Empagliflozin recently received an FDA indication as a medication for use in reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease, the first drug for type 2 diabetes to do so.
The label includes information of the drug’s four doses, all of which contain 1,000 mg of metformin plus empagliflozin in strengths of 5 mg, 10 mg, 12.5 mg, and 25 mg.
Among patients who are already taking metformin and plan to begin a regimen of Synjardy XR, their best choice is to switch to the formulation containing a similar daily dose of metformin and a total daily dose of 10 mg empagliflozin. Those already on empagliflozin should switch to Synjardy XR containing the same daily dose of empagliflozin and a total daily dose of 1,000 mg metformin. Dosing may be adjusted upward on the basis of effectiveness and tolerability up to a maximum of 25 mg empagliflozin/2,000 mg metformin, taken once daily with a meal in the morning.
Synjardy XR is contraindicated in patients with an estimated glomerular filtration rate of less than 45 mL/min per 1.73 m2. Renal function should be assessed in patients with impaired renal function before taking Synjardy XR.
Several clinical trials tested coadministration of metformin and empagliflozin. In the largest, 637 patients with type 2 diabetes who were inadequately controlled (hemoglobin A1c of 7%-10%) with 1,500 mg metformin were randomized to receive placebo, 10 mg empagliflozin, or 25 mg empagliflozin for 24 weeks. Both the 10-mg and 25-mg dosages of empagliflozin resulted in significant reductions compared with placebo in HbA1c (–0.7% and –0.8%, respectively) fasting glucose (–26 mg/dL and –29 mg/dL), and body weight (–2 kg and –2.5 kg).
The single-pill formulation of Synjardy XR was not tested in clinical trials for efficacy; however, several trials performed in healthy subjects showed bioequivalence of the fixed dose combination, compared with separate pills.
[email protected]
for use in the management of blood sugar in adults with type 2 diabetes. The drug, to be marketed as Synjardy XR by Boehringer Ingelheim and Eli Lilly, is intended for use with a diet and exercise program.
Its standard release formulation was approved in August 2015.
FDA approved the extended-release version on Dec. 12. The updated label includes a boxed warning regarding the risk of metformin-associated lactic acidosis
Empagliflozin recently received an FDA indication as a medication for use in reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease, the first drug for type 2 diabetes to do so.
The label includes information of the drug’s four doses, all of which contain 1,000 mg of metformin plus empagliflozin in strengths of 5 mg, 10 mg, 12.5 mg, and 25 mg.
Among patients who are already taking metformin and plan to begin a regimen of Synjardy XR, their best choice is to switch to the formulation containing a similar daily dose of metformin and a total daily dose of 10 mg empagliflozin. Those already on empagliflozin should switch to Synjardy XR containing the same daily dose of empagliflozin and a total daily dose of 1,000 mg metformin. Dosing may be adjusted upward on the basis of effectiveness and tolerability up to a maximum of 25 mg empagliflozin/2,000 mg metformin, taken once daily with a meal in the morning.
Synjardy XR is contraindicated in patients with an estimated glomerular filtration rate of less than 45 mL/min per 1.73 m2. Renal function should be assessed in patients with impaired renal function before taking Synjardy XR.
Several clinical trials tested coadministration of metformin and empagliflozin. In the largest, 637 patients with type 2 diabetes who were inadequately controlled (hemoglobin A1c of 7%-10%) with 1,500 mg metformin were randomized to receive placebo, 10 mg empagliflozin, or 25 mg empagliflozin for 24 weeks. Both the 10-mg and 25-mg dosages of empagliflozin resulted in significant reductions compared with placebo in HbA1c (–0.7% and –0.8%, respectively) fasting glucose (–26 mg/dL and –29 mg/dL), and body weight (–2 kg and –2.5 kg).
The single-pill formulation of Synjardy XR was not tested in clinical trials for efficacy; however, several trials performed in healthy subjects showed bioequivalence of the fixed dose combination, compared with separate pills.
[email protected]
Cooling device reduces breast cancer–related alopecia during chemotherapy
SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.
Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.
The study was stopped after the interim analysis because of the positive superiority in the treatment group, Dr. Nangia said.
Study subjects were women with early-stage breast cancer and planned neoadjuvant or adjuvant chemotherapy. Most (65%) received taxane-based chemotherapy and 35% received anthracycline-based chemotherapy; the latter has been shown to be associated with higher rates of hair loss.
The OPHLPS system involves the use of a “cold cap” that is cooled using a refrigeration system and fitted to a patient’s head during chemotherapy treatment. For the current study, subjects underwent scalp cooling for 30 minutes before chemotherapy, during chemotherapy, and for 90 minutes after.
Most subjects (39%-52%) reported that they were reasonably comfortable during use of the device during treatment cycles 1-4. Only 2.4% reported being very uncomfortable, and that was only during cycle 2.
An analysis based on type of therapy showed that 65.1% of those receiving a taxane experienced hair preservation, compared with 21.9% of those receiving an anthracycline.
Scalp cooling, which reduces blood flow and chemoexposure to the hair follicles and thereby reduces hair loss, is widely used in Europe and, despite a great deal of interest in the technology in the United States, the Food and Drug Administration has been slow to get on board because of concerns over the potential for scalp metastasis. However, long-term outcomes data from Europe demonstrate that scalp metastasis is “exceedingly rare” and has occurred only in those with metastasis throughout the body, Dr. Nangia said.
Those data opened the door to the current study – the first prospective randomized trial of scalp-cooling.
In response to questions about the effects of scalp cooling across additional chemotherapy cycles (for example, those who undergo eight cycles), Dr. Nangia said that all patients completed four cycles, and data for those with eight cycles planned will be included in a final analysis.
“In other countries, they do have success rates with eight cycles, which is standard for some women,” she said. SCALP trial subjects will also be followed for 5 years to monitor overall survival, recurrence of cancer, and potential metastasis to the scalp, she said.
Based on the findings of the study, the maker of the device is seeking FDA clearance. If approved, the OPHLPS would compete with the DigniCap (Dignitana), which has already received approval.
“Scalp cooling devices are highly effective and should become available to women with breast cancer receiving chemotherapy ... Further study should be done exploring the technology for other types of tumors and with other chemotherapy regimens. More study looking at the impact of chemotherapy-induced alopecia on psyche and body image should be performed as well,” Dr. Nangia concluded, noting that tailored quality-of-life tools are needed to evaluate the impact of alopecia on quality of life.
Dr. Nangia reported receiving research funding from Paxman, the sponsor of the study, to her institution.
SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.
Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.
The study was stopped after the interim analysis because of the positive superiority in the treatment group, Dr. Nangia said.
Study subjects were women with early-stage breast cancer and planned neoadjuvant or adjuvant chemotherapy. Most (65%) received taxane-based chemotherapy and 35% received anthracycline-based chemotherapy; the latter has been shown to be associated with higher rates of hair loss.
The OPHLPS system involves the use of a “cold cap” that is cooled using a refrigeration system and fitted to a patient’s head during chemotherapy treatment. For the current study, subjects underwent scalp cooling for 30 minutes before chemotherapy, during chemotherapy, and for 90 minutes after.
Most subjects (39%-52%) reported that they were reasonably comfortable during use of the device during treatment cycles 1-4. Only 2.4% reported being very uncomfortable, and that was only during cycle 2.
An analysis based on type of therapy showed that 65.1% of those receiving a taxane experienced hair preservation, compared with 21.9% of those receiving an anthracycline.
Scalp cooling, which reduces blood flow and chemoexposure to the hair follicles and thereby reduces hair loss, is widely used in Europe and, despite a great deal of interest in the technology in the United States, the Food and Drug Administration has been slow to get on board because of concerns over the potential for scalp metastasis. However, long-term outcomes data from Europe demonstrate that scalp metastasis is “exceedingly rare” and has occurred only in those with metastasis throughout the body, Dr. Nangia said.
Those data opened the door to the current study – the first prospective randomized trial of scalp-cooling.
In response to questions about the effects of scalp cooling across additional chemotherapy cycles (for example, those who undergo eight cycles), Dr. Nangia said that all patients completed four cycles, and data for those with eight cycles planned will be included in a final analysis.
“In other countries, they do have success rates with eight cycles, which is standard for some women,” she said. SCALP trial subjects will also be followed for 5 years to monitor overall survival, recurrence of cancer, and potential metastasis to the scalp, she said.
Based on the findings of the study, the maker of the device is seeking FDA clearance. If approved, the OPHLPS would compete with the DigniCap (Dignitana), which has already received approval.
“Scalp cooling devices are highly effective and should become available to women with breast cancer receiving chemotherapy ... Further study should be done exploring the technology for other types of tumors and with other chemotherapy regimens. More study looking at the impact of chemotherapy-induced alopecia on psyche and body image should be performed as well,” Dr. Nangia concluded, noting that tailored quality-of-life tools are needed to evaluate the impact of alopecia on quality of life.
Dr. Nangia reported receiving research funding from Paxman, the sponsor of the study, to her institution.
SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.
Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.
The study was stopped after the interim analysis because of the positive superiority in the treatment group, Dr. Nangia said.
Study subjects were women with early-stage breast cancer and planned neoadjuvant or adjuvant chemotherapy. Most (65%) received taxane-based chemotherapy and 35% received anthracycline-based chemotherapy; the latter has been shown to be associated with higher rates of hair loss.
The OPHLPS system involves the use of a “cold cap” that is cooled using a refrigeration system and fitted to a patient’s head during chemotherapy treatment. For the current study, subjects underwent scalp cooling for 30 minutes before chemotherapy, during chemotherapy, and for 90 minutes after.
Most subjects (39%-52%) reported that they were reasonably comfortable during use of the device during treatment cycles 1-4. Only 2.4% reported being very uncomfortable, and that was only during cycle 2.
An analysis based on type of therapy showed that 65.1% of those receiving a taxane experienced hair preservation, compared with 21.9% of those receiving an anthracycline.
Scalp cooling, which reduces blood flow and chemoexposure to the hair follicles and thereby reduces hair loss, is widely used in Europe and, despite a great deal of interest in the technology in the United States, the Food and Drug Administration has been slow to get on board because of concerns over the potential for scalp metastasis. However, long-term outcomes data from Europe demonstrate that scalp metastasis is “exceedingly rare” and has occurred only in those with metastasis throughout the body, Dr. Nangia said.
Those data opened the door to the current study – the first prospective randomized trial of scalp-cooling.
In response to questions about the effects of scalp cooling across additional chemotherapy cycles (for example, those who undergo eight cycles), Dr. Nangia said that all patients completed four cycles, and data for those with eight cycles planned will be included in a final analysis.
“In other countries, they do have success rates with eight cycles, which is standard for some women,” she said. SCALP trial subjects will also be followed for 5 years to monitor overall survival, recurrence of cancer, and potential metastasis to the scalp, she said.
Based on the findings of the study, the maker of the device is seeking FDA clearance. If approved, the OPHLPS would compete with the DigniCap (Dignitana), which has already received approval.
“Scalp cooling devices are highly effective and should become available to women with breast cancer receiving chemotherapy ... Further study should be done exploring the technology for other types of tumors and with other chemotherapy regimens. More study looking at the impact of chemotherapy-induced alopecia on psyche and body image should be performed as well,” Dr. Nangia concluded, noting that tailored quality-of-life tools are needed to evaluate the impact of alopecia on quality of life.
Dr. Nangia reported receiving research funding from Paxman, the sponsor of the study, to her institution.
AT SABCS 2016
Key clinical point:
Major finding: 50.5% of treated patients experienced no more than grade 1 alopecia (less than 50% hair loss), compared with 0% of control subjects.
Data source: The prospective, randomized SCALP trial involving 182 women.
Disclosures: Dr. Nangia reported receiving research funding from Paxman, sponsor of the study, to her institution.
FDA affirms bladder cancer warning with diabetes drug
Though a 10-year epidemiologic study did not find an increased risk of bladder cancer with pioglitazone use, the Food and Drug Administration has chosen to affirm the warning on the label of the type 2 diabetes drug following an updated review of several studies.
The FDA issued a warning about the possible risk of bladder cancer based on interim results from the 10-year epidemiologic study in 2010, and it changed the labels of pioglitazone-containing medicines in 2011 to include warnings about this risk.
There was a modest trend toward higher risk with increasing duration of use, but the trend was not statistically significant. Compared with the interim 5-year results, these final 10-year results found weaker associations that were not statistically significant.
The directions of the associations, however, remained unchanged. Based on these findings and other reviewed studies with conflicting results, the FDA has concluded that use of pioglitazone may be linked to an increased risk of bladder cancer.
The labels of pioglitazone-containing medicines already contain warnings about this risk, but the FDA has now approved label updates to describe the additional studies reviewed.
Read the FDA update and data summary here.
[email protected]
On Twitter @nikolaideslaura
Though a 10-year epidemiologic study did not find an increased risk of bladder cancer with pioglitazone use, the Food and Drug Administration has chosen to affirm the warning on the label of the type 2 diabetes drug following an updated review of several studies.
The FDA issued a warning about the possible risk of bladder cancer based on interim results from the 10-year epidemiologic study in 2010, and it changed the labels of pioglitazone-containing medicines in 2011 to include warnings about this risk.
There was a modest trend toward higher risk with increasing duration of use, but the trend was not statistically significant. Compared with the interim 5-year results, these final 10-year results found weaker associations that were not statistically significant.
The directions of the associations, however, remained unchanged. Based on these findings and other reviewed studies with conflicting results, the FDA has concluded that use of pioglitazone may be linked to an increased risk of bladder cancer.
The labels of pioglitazone-containing medicines already contain warnings about this risk, but the FDA has now approved label updates to describe the additional studies reviewed.
Read the FDA update and data summary here.
[email protected]
On Twitter @nikolaideslaura
Though a 10-year epidemiologic study did not find an increased risk of bladder cancer with pioglitazone use, the Food and Drug Administration has chosen to affirm the warning on the label of the type 2 diabetes drug following an updated review of several studies.
The FDA issued a warning about the possible risk of bladder cancer based on interim results from the 10-year epidemiologic study in 2010, and it changed the labels of pioglitazone-containing medicines in 2011 to include warnings about this risk.
There was a modest trend toward higher risk with increasing duration of use, but the trend was not statistically significant. Compared with the interim 5-year results, these final 10-year results found weaker associations that were not statistically significant.
The directions of the associations, however, remained unchanged. Based on these findings and other reviewed studies with conflicting results, the FDA has concluded that use of pioglitazone may be linked to an increased risk of bladder cancer.
The labels of pioglitazone-containing medicines already contain warnings about this risk, but the FDA has now approved label updates to describe the additional studies reviewed.
Read the FDA update and data summary here.
[email protected]
On Twitter @nikolaideslaura
HIV research update: Late November 2016
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
There has been a significant increase over time in the proportion of deliveries to women living with HIV aged 40 years and older, which has implications for pregnancy management, according to a study in HIV Medicine.
HIV-positive older adults have higher cystatin C levels than do HIV-negative older adults, according to a recent study, and cystatin C may be associated with neurocognitive impairment in this population, particularly if they use tenofovir.
A low Infant and Child Feeding Index, dietary diversity, and food consistency scores were likely associated with increased risk of diarrhea and acute respiratory infection among HIV-exposed infants in Tanzania, according to a study in JAIDS.
A Pediatric HIV/AIDS Cohort Study of HIV-exposed, uninfected U.S. children found growth was above average, although maternal tenofovir use was not associated with lower length or head circumference at 2 years of age, as hypothesized.
Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol, according to a study published in JAIDS.
Antiretroviral therapy during pregnancy was not associated with preterm birth, a recent study found, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth.
A large majority of HIV-negative gay and bisexual men were appropriate candidates for PrEP, yet less than 1 in 10 were using and adherent to PrEP, according to a study in JAIDS. The findings highlight the need for interventions tailored to address the unique barriers men face at each stage of the care cascade.
Men who have sex with men remain a high risk group for HIV infection in a low prevalence setting, according to a study in Istanbul, and thus represent a key target population for diagnostic and therapeutic interventions.
A Kenya-based study found there is an urgent need to implement HIV prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts less than 100 cells/mcL), to optimize the impact of HIV prevention, care, and treatment in resource scarce settings.
A recent Nigerian study found evidence of a rising tide of HIV infection in TB patients, in particular among single middle-aged women with low education.
Negative emotional states with significant severity were common among people living with HIV, particularly depression and anxiety, according to a study in HIV & AIDS Review.
Drug-drug interactions between direct-acting antivirals and antiretroviral therapy are frequently found among HIV/HCV-coinfected patients, according to a study in HIV Medicine.
Key pretreatment viral resistant-associated variants (RAVs) for hepatitis C protease inhibitors are present in a major portion of the HCV/HIV coinfected population prior to therapy, a recent study found.
[email protected]
On Twitter @richpizzi
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
There has been a significant increase over time in the proportion of deliveries to women living with HIV aged 40 years and older, which has implications for pregnancy management, according to a study in HIV Medicine.
HIV-positive older adults have higher cystatin C levels than do HIV-negative older adults, according to a recent study, and cystatin C may be associated with neurocognitive impairment in this population, particularly if they use tenofovir.
A low Infant and Child Feeding Index, dietary diversity, and food consistency scores were likely associated with increased risk of diarrhea and acute respiratory infection among HIV-exposed infants in Tanzania, according to a study in JAIDS.
A Pediatric HIV/AIDS Cohort Study of HIV-exposed, uninfected U.S. children found growth was above average, although maternal tenofovir use was not associated with lower length or head circumference at 2 years of age, as hypothesized.
Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol, according to a study published in JAIDS.
Antiretroviral therapy during pregnancy was not associated with preterm birth, a recent study found, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth.
A large majority of HIV-negative gay and bisexual men were appropriate candidates for PrEP, yet less than 1 in 10 were using and adherent to PrEP, according to a study in JAIDS. The findings highlight the need for interventions tailored to address the unique barriers men face at each stage of the care cascade.
Men who have sex with men remain a high risk group for HIV infection in a low prevalence setting, according to a study in Istanbul, and thus represent a key target population for diagnostic and therapeutic interventions.
A Kenya-based study found there is an urgent need to implement HIV prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts less than 100 cells/mcL), to optimize the impact of HIV prevention, care, and treatment in resource scarce settings.
A recent Nigerian study found evidence of a rising tide of HIV infection in TB patients, in particular among single middle-aged women with low education.
Negative emotional states with significant severity were common among people living with HIV, particularly depression and anxiety, according to a study in HIV & AIDS Review.
Drug-drug interactions between direct-acting antivirals and antiretroviral therapy are frequently found among HIV/HCV-coinfected patients, according to a study in HIV Medicine.
Key pretreatment viral resistant-associated variants (RAVs) for hepatitis C protease inhibitors are present in a major portion of the HCV/HIV coinfected population prior to therapy, a recent study found.
[email protected]
On Twitter @richpizzi
A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
There has been a significant increase over time in the proportion of deliveries to women living with HIV aged 40 years and older, which has implications for pregnancy management, according to a study in HIV Medicine.
HIV-positive older adults have higher cystatin C levels than do HIV-negative older adults, according to a recent study, and cystatin C may be associated with neurocognitive impairment in this population, particularly if they use tenofovir.
A low Infant and Child Feeding Index, dietary diversity, and food consistency scores were likely associated with increased risk of diarrhea and acute respiratory infection among HIV-exposed infants in Tanzania, according to a study in JAIDS.
A Pediatric HIV/AIDS Cohort Study of HIV-exposed, uninfected U.S. children found growth was above average, although maternal tenofovir use was not associated with lower length or head circumference at 2 years of age, as hypothesized.
Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol, according to a study published in JAIDS.
Antiretroviral therapy during pregnancy was not associated with preterm birth, a recent study found, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth.
A large majority of HIV-negative gay and bisexual men were appropriate candidates for PrEP, yet less than 1 in 10 were using and adherent to PrEP, according to a study in JAIDS. The findings highlight the need for interventions tailored to address the unique barriers men face at each stage of the care cascade.
Men who have sex with men remain a high risk group for HIV infection in a low prevalence setting, according to a study in Istanbul, and thus represent a key target population for diagnostic and therapeutic interventions.
A Kenya-based study found there is an urgent need to implement HIV prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts less than 100 cells/mcL), to optimize the impact of HIV prevention, care, and treatment in resource scarce settings.
A recent Nigerian study found evidence of a rising tide of HIV infection in TB patients, in particular among single middle-aged women with low education.
Negative emotional states with significant severity were common among people living with HIV, particularly depression and anxiety, according to a study in HIV & AIDS Review.
Drug-drug interactions between direct-acting antivirals and antiretroviral therapy are frequently found among HIV/HCV-coinfected patients, according to a study in HIV Medicine.
Key pretreatment viral resistant-associated variants (RAVs) for hepatitis C protease inhibitors are present in a major portion of the HCV/HIV coinfected population prior to therapy, a recent study found.
[email protected]
On Twitter @richpizzi