User login
How to Keep Pace With Genetic Advances in Movement Disorders
VANCOUVER—Researchers’ understanding of genetic causes of movement disorders is advancing rapidly. “The ability to generate data has almost surpassed our ability to understand and use it in the clinic,” said Buz Jinnah, MD, PhD, at the 21st International Congress of Parkinson’s Disease and Movement Disorders.
A recent study underscores the swift evolution of the field. Investigators compared the diagnostic ability of a dystonia gene panel with that of experts who formulated a diagnostic workup without the use of gene panel analysis. In a cohort of 61 patients, the gene panel led to more genetic diagnoses and did so faster and at less cost on average, compared with experts using traditional methods.
Neurologists face practical questions, such as which patients need genetic testing, which tests they should perform, and how the results influence clinical management, said Dr. Jinnah, Professor of Neurology, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta. Neurologists once considered Wilson’s disease to have the only genetic cause of movement disorders that significantly changed treatment. Now, researchers have identified more than 30 genetic movement disorders with specific, effective treatments.
Does a Patient Need Genetic Testing?
Not all patients need genetic testing. In some cases, the need for genetic testing is obvious, but in other cases, it is not so clear, Dr. Jinnah said. Certain features increase suspicion for a genetic disorder, such as family history, unusually young age of onset, and combinations of features that fit a recognized syndrome.
Genetic testing also may be warranted in presumed acquired cases. “Methodical studies of these so-called acquired cases reveal a high proportion of genetic explanation for them,” he said. “We typically think of cerebral palsy as an acquired disorder…. But the studies are now showing that about a third of these cases have a genetic explanation.”
Single-gene sequencing, chromosomal microarray, and tests for deletions or insertions are available, as well as next-generation sequencing methods with broader reach. Next-generation techniques include gene panels that can test hundreds of genes associated with a disease, whole-exome sequencing, and whole-genome sequencing.
Choosing a Test
Experts tend to use one of three strategies to select which genetic test to perform. One approach entails identifying red flags—“telltale clinical features that point to a specific diagnosis or group of diagnoses,” said Dr. Jinnah.
Another approach involves pattern recognition. Syndromic combinations may lead a neurologist “straight to a single gene test to confirm the diagnosis” if a patient has a classic presentation of a genetic disease.
The third approach uses diagnostic algorithms. “Depending on the presence or absence of various clinical features … [an algorithm] tells you which gene or collection of genes you need to test for,” he said.
Each strategy has limitations, however. It is difficult to remember all of the red flags and syndromic patterns, and many disorders lack red flags. Atypical syndromes can be misleading, and atypical presentations that have been reported in the literature for decades “continue to surprise us,” Dr. Jinnah said. Researchers have published various diagnostic algorithms for dystonia, parkinsonism, and ataxia, and none of them is perfect.
Several studies have shown the potential of next-generation genetic testing. A report from the NIH’s Undiagnosed Diseases Program found that 25% of patients in the program reached a diagnosis within a few weeks using whole-exome sequencing. “Their conclusion was that these agnostic methods need to be used earlier in the diagnostic process,” he said.
A similar study in Canada evaluated the use of whole-exome sequencing in 362 children with disorders that experts had not been able to diagnose. About 30% of the patients received a definitive diagnosis using whole-exome sequencing.
Clinical Implications
Genetic testing may be important for patient counseling. For instance, if a patient has a family history of Huntington’s disease and develops symptoms suggestive of Huntington’s disease, a normal test result is therapeutic, Dr. Jinnah said. Normal results may be false negatives, however. For example, next-generation sequencing methods are not suitable for detecting certain problems like large insertions, duplications, triplet disorders, and certain genes, and neurologists should consider whether other tests may be useful.
If a genetic test yields a pathologic result, it can inform prognosis and guide family counseling and planning. Furthermore, some inherited disorders have life-altering treatments.
Neurologists are familiar with typical and atypical presentations of Wilson’s disease because the disorder has highly effective treatments. But recent studies have identified lesser-known disorders that may be equally important to recognize. “How many of us are routinely testing these same cases for disorders of manganese transporters?” Dr. Jinnah asked. “It is relatively new information, but the clinical scenario is virtually identical.”
The International Parkinson and Movement Disorder Society’s Rare Movement Disorders Task Force sought to determine how many treatable genetic movement disorders have been identified. The task force found more than 30 disorders with specific treatments—including vitamins, dietary interventions, trigger avoidance, and drugs—that can have “a dramatic impact on the patient’s clinical course,” Dr. Jinnah said. “All of them are quite rare, but we do not want to miss them, because they are treatable.” Investigators identify more treatable disorders each year.
Interpreting Ambiguous Results
Another practical concern for neurologists is the interpretation of variants of unknown significance (VOUS) in genetic test results. “It means that a change or variant in the normal gene was discovered by the laboratory, but the change has never been described in association with the disease that you are interested in,” Dr. Jinnah said. “As a result, the laboratory cannot tell you whether it is relevant or not.”
Neurologists might be inclined to tell a patient that they “found something weird in their DNA,” but this approach “consolidates the patient’s concern that they have some mysterious disorder that none of the doctors can figure out, even the experts,” he said. Nor should neurologists tell a patient that the VOUS is not significant, because that is not what VOUS means.
A VOUS is comparable to a radiology report that says, “Clinical correlation is advised.” That phrase leads neurologists to compare neuroimaging to the clinical phenotype and ask whether the imaging findings make sense. “A VOUS is no different from this,” he said. Neurologists cannot explain all genetic variants, just as neurologists cannot explain all of the spots on a brain scan. “We have to get comfortable with the fact that we do not have answers for everything and that there will be some ambiguities when we are done.”
Genetics is logical and straightforward, and educational sessions are available at conferences for neurologists who are interested in learning more about genetic testing, Dr. Jinnah said. Neurologists also can refer patients to experts. “This referral must be a collaboration,” he said. “People in human genetics are not trained in movement disorders, and many of them have no formal training in neurology. They need your careful phenotypic exam to point them in th
Genetic testing often is expensive, not readily available, and not covered by insurance, but this situation may change, Dr. Jinnah said. He likened the situation of genetic testing today to that of MRI in the 1980s. “Only a few centers in the world had [MRI]. It was extremely expensive. Now, MRI scanners are everywhere, and everybody uses it because it is so valuable in clinical medicine,” he said. “I suspect that in a few years, we will see the same with genetic tests.”
—Jake Remaly
Suggested Reading
Charlesworth G, Bhatia KP, Wood NW. The genetics of dystonia: new twists in an old tale. Brain. 2013;136(Pt 7):2017-2037.
Gahl WA, Tifft CJ. The NIH Undiagnosed Diseases Program: lessons learned. JAMA. 2011;305(18):1904-1905.
Olgiati S, Quadri M, Bonifati V. Genetics of movement disorders in the next-generation sequencing era. Mov Disord. 2016;31(4):458-470.
Sawyer SL, Hartley T, Dyment DA, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016;89(3):275-284.
van Egmond ME, Lugtenberg CHA, Brouwer OF, et al. A post hoc study on gene panel analysis for the diagnosis of dystonia. Mov Disord. 2017;32(4):569-575.
VANCOUVER—Researchers’ understanding of genetic causes of movement disorders is advancing rapidly. “The ability to generate data has almost surpassed our ability to understand and use it in the clinic,” said Buz Jinnah, MD, PhD, at the 21st International Congress of Parkinson’s Disease and Movement Disorders.
A recent study underscores the swift evolution of the field. Investigators compared the diagnostic ability of a dystonia gene panel with that of experts who formulated a diagnostic workup without the use of gene panel analysis. In a cohort of 61 patients, the gene panel led to more genetic diagnoses and did so faster and at less cost on average, compared with experts using traditional methods.
Neurologists face practical questions, such as which patients need genetic testing, which tests they should perform, and how the results influence clinical management, said Dr. Jinnah, Professor of Neurology, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta. Neurologists once considered Wilson’s disease to have the only genetic cause of movement disorders that significantly changed treatment. Now, researchers have identified more than 30 genetic movement disorders with specific, effective treatments.
Does a Patient Need Genetic Testing?
Not all patients need genetic testing. In some cases, the need for genetic testing is obvious, but in other cases, it is not so clear, Dr. Jinnah said. Certain features increase suspicion for a genetic disorder, such as family history, unusually young age of onset, and combinations of features that fit a recognized syndrome.
Genetic testing also may be warranted in presumed acquired cases. “Methodical studies of these so-called acquired cases reveal a high proportion of genetic explanation for them,” he said. “We typically think of cerebral palsy as an acquired disorder…. But the studies are now showing that about a third of these cases have a genetic explanation.”
Single-gene sequencing, chromosomal microarray, and tests for deletions or insertions are available, as well as next-generation sequencing methods with broader reach. Next-generation techniques include gene panels that can test hundreds of genes associated with a disease, whole-exome sequencing, and whole-genome sequencing.
Choosing a Test
Experts tend to use one of three strategies to select which genetic test to perform. One approach entails identifying red flags—“telltale clinical features that point to a specific diagnosis or group of diagnoses,” said Dr. Jinnah.
Another approach involves pattern recognition. Syndromic combinations may lead a neurologist “straight to a single gene test to confirm the diagnosis” if a patient has a classic presentation of a genetic disease.
The third approach uses diagnostic algorithms. “Depending on the presence or absence of various clinical features … [an algorithm] tells you which gene or collection of genes you need to test for,” he said.
Each strategy has limitations, however. It is difficult to remember all of the red flags and syndromic patterns, and many disorders lack red flags. Atypical syndromes can be misleading, and atypical presentations that have been reported in the literature for decades “continue to surprise us,” Dr. Jinnah said. Researchers have published various diagnostic algorithms for dystonia, parkinsonism, and ataxia, and none of them is perfect.
Several studies have shown the potential of next-generation genetic testing. A report from the NIH’s Undiagnosed Diseases Program found that 25% of patients in the program reached a diagnosis within a few weeks using whole-exome sequencing. “Their conclusion was that these agnostic methods need to be used earlier in the diagnostic process,” he said.
A similar study in Canada evaluated the use of whole-exome sequencing in 362 children with disorders that experts had not been able to diagnose. About 30% of the patients received a definitive diagnosis using whole-exome sequencing.
Clinical Implications
Genetic testing may be important for patient counseling. For instance, if a patient has a family history of Huntington’s disease and develops symptoms suggestive of Huntington’s disease, a normal test result is therapeutic, Dr. Jinnah said. Normal results may be false negatives, however. For example, next-generation sequencing methods are not suitable for detecting certain problems like large insertions, duplications, triplet disorders, and certain genes, and neurologists should consider whether other tests may be useful.
If a genetic test yields a pathologic result, it can inform prognosis and guide family counseling and planning. Furthermore, some inherited disorders have life-altering treatments.
Neurologists are familiar with typical and atypical presentations of Wilson’s disease because the disorder has highly effective treatments. But recent studies have identified lesser-known disorders that may be equally important to recognize. “How many of us are routinely testing these same cases for disorders of manganese transporters?” Dr. Jinnah asked. “It is relatively new information, but the clinical scenario is virtually identical.”
The International Parkinson and Movement Disorder Society’s Rare Movement Disorders Task Force sought to determine how many treatable genetic movement disorders have been identified. The task force found more than 30 disorders with specific treatments—including vitamins, dietary interventions, trigger avoidance, and drugs—that can have “a dramatic impact on the patient’s clinical course,” Dr. Jinnah said. “All of them are quite rare, but we do not want to miss them, because they are treatable.” Investigators identify more treatable disorders each year.
Interpreting Ambiguous Results
Another practical concern for neurologists is the interpretation of variants of unknown significance (VOUS) in genetic test results. “It means that a change or variant in the normal gene was discovered by the laboratory, but the change has never been described in association with the disease that you are interested in,” Dr. Jinnah said. “As a result, the laboratory cannot tell you whether it is relevant or not.”
Neurologists might be inclined to tell a patient that they “found something weird in their DNA,” but this approach “consolidates the patient’s concern that they have some mysterious disorder that none of the doctors can figure out, even the experts,” he said. Nor should neurologists tell a patient that the VOUS is not significant, because that is not what VOUS means.
A VOUS is comparable to a radiology report that says, “Clinical correlation is advised.” That phrase leads neurologists to compare neuroimaging to the clinical phenotype and ask whether the imaging findings make sense. “A VOUS is no different from this,” he said. Neurologists cannot explain all genetic variants, just as neurologists cannot explain all of the spots on a brain scan. “We have to get comfortable with the fact that we do not have answers for everything and that there will be some ambiguities when we are done.”
Genetics is logical and straightforward, and educational sessions are available at conferences for neurologists who are interested in learning more about genetic testing, Dr. Jinnah said. Neurologists also can refer patients to experts. “This referral must be a collaboration,” he said. “People in human genetics are not trained in movement disorders, and many of them have no formal training in neurology. They need your careful phenotypic exam to point them in th
Genetic testing often is expensive, not readily available, and not covered by insurance, but this situation may change, Dr. Jinnah said. He likened the situation of genetic testing today to that of MRI in the 1980s. “Only a few centers in the world had [MRI]. It was extremely expensive. Now, MRI scanners are everywhere, and everybody uses it because it is so valuable in clinical medicine,” he said. “I suspect that in a few years, we will see the same with genetic tests.”
—Jake Remaly
Suggested Reading
Charlesworth G, Bhatia KP, Wood NW. The genetics of dystonia: new twists in an old tale. Brain. 2013;136(Pt 7):2017-2037.
Gahl WA, Tifft CJ. The NIH Undiagnosed Diseases Program: lessons learned. JAMA. 2011;305(18):1904-1905.
Olgiati S, Quadri M, Bonifati V. Genetics of movement disorders in the next-generation sequencing era. Mov Disord. 2016;31(4):458-470.
Sawyer SL, Hartley T, Dyment DA, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016;89(3):275-284.
van Egmond ME, Lugtenberg CHA, Brouwer OF, et al. A post hoc study on gene panel analysis for the diagnosis of dystonia. Mov Disord. 2017;32(4):569-575.
VANCOUVER—Researchers’ understanding of genetic causes of movement disorders is advancing rapidly. “The ability to generate data has almost surpassed our ability to understand and use it in the clinic,” said Buz Jinnah, MD, PhD, at the 21st International Congress of Parkinson’s Disease and Movement Disorders.
A recent study underscores the swift evolution of the field. Investigators compared the diagnostic ability of a dystonia gene panel with that of experts who formulated a diagnostic workup without the use of gene panel analysis. In a cohort of 61 patients, the gene panel led to more genetic diagnoses and did so faster and at less cost on average, compared with experts using traditional methods.
Neurologists face practical questions, such as which patients need genetic testing, which tests they should perform, and how the results influence clinical management, said Dr. Jinnah, Professor of Neurology, Human Genetics, and Pediatrics at Emory University School of Medicine in Atlanta. Neurologists once considered Wilson’s disease to have the only genetic cause of movement disorders that significantly changed treatment. Now, researchers have identified more than 30 genetic movement disorders with specific, effective treatments.
Does a Patient Need Genetic Testing?
Not all patients need genetic testing. In some cases, the need for genetic testing is obvious, but in other cases, it is not so clear, Dr. Jinnah said. Certain features increase suspicion for a genetic disorder, such as family history, unusually young age of onset, and combinations of features that fit a recognized syndrome.
Genetic testing also may be warranted in presumed acquired cases. “Methodical studies of these so-called acquired cases reveal a high proportion of genetic explanation for them,” he said. “We typically think of cerebral palsy as an acquired disorder…. But the studies are now showing that about a third of these cases have a genetic explanation.”
Single-gene sequencing, chromosomal microarray, and tests for deletions or insertions are available, as well as next-generation sequencing methods with broader reach. Next-generation techniques include gene panels that can test hundreds of genes associated with a disease, whole-exome sequencing, and whole-genome sequencing.
Choosing a Test
Experts tend to use one of three strategies to select which genetic test to perform. One approach entails identifying red flags—“telltale clinical features that point to a specific diagnosis or group of diagnoses,” said Dr. Jinnah.
Another approach involves pattern recognition. Syndromic combinations may lead a neurologist “straight to a single gene test to confirm the diagnosis” if a patient has a classic presentation of a genetic disease.
The third approach uses diagnostic algorithms. “Depending on the presence or absence of various clinical features … [an algorithm] tells you which gene or collection of genes you need to test for,” he said.
Each strategy has limitations, however. It is difficult to remember all of the red flags and syndromic patterns, and many disorders lack red flags. Atypical syndromes can be misleading, and atypical presentations that have been reported in the literature for decades “continue to surprise us,” Dr. Jinnah said. Researchers have published various diagnostic algorithms for dystonia, parkinsonism, and ataxia, and none of them is perfect.
Several studies have shown the potential of next-generation genetic testing. A report from the NIH’s Undiagnosed Diseases Program found that 25% of patients in the program reached a diagnosis within a few weeks using whole-exome sequencing. “Their conclusion was that these agnostic methods need to be used earlier in the diagnostic process,” he said.
A similar study in Canada evaluated the use of whole-exome sequencing in 362 children with disorders that experts had not been able to diagnose. About 30% of the patients received a definitive diagnosis using whole-exome sequencing.
Clinical Implications
Genetic testing may be important for patient counseling. For instance, if a patient has a family history of Huntington’s disease and develops symptoms suggestive of Huntington’s disease, a normal test result is therapeutic, Dr. Jinnah said. Normal results may be false negatives, however. For example, next-generation sequencing methods are not suitable for detecting certain problems like large insertions, duplications, triplet disorders, and certain genes, and neurologists should consider whether other tests may be useful.
If a genetic test yields a pathologic result, it can inform prognosis and guide family counseling and planning. Furthermore, some inherited disorders have life-altering treatments.
Neurologists are familiar with typical and atypical presentations of Wilson’s disease because the disorder has highly effective treatments. But recent studies have identified lesser-known disorders that may be equally important to recognize. “How many of us are routinely testing these same cases for disorders of manganese transporters?” Dr. Jinnah asked. “It is relatively new information, but the clinical scenario is virtually identical.”
The International Parkinson and Movement Disorder Society’s Rare Movement Disorders Task Force sought to determine how many treatable genetic movement disorders have been identified. The task force found more than 30 disorders with specific treatments—including vitamins, dietary interventions, trigger avoidance, and drugs—that can have “a dramatic impact on the patient’s clinical course,” Dr. Jinnah said. “All of them are quite rare, but we do not want to miss them, because they are treatable.” Investigators identify more treatable disorders each year.
Interpreting Ambiguous Results
Another practical concern for neurologists is the interpretation of variants of unknown significance (VOUS) in genetic test results. “It means that a change or variant in the normal gene was discovered by the laboratory, but the change has never been described in association with the disease that you are interested in,” Dr. Jinnah said. “As a result, the laboratory cannot tell you whether it is relevant or not.”
Neurologists might be inclined to tell a patient that they “found something weird in their DNA,” but this approach “consolidates the patient’s concern that they have some mysterious disorder that none of the doctors can figure out, even the experts,” he said. Nor should neurologists tell a patient that the VOUS is not significant, because that is not what VOUS means.
A VOUS is comparable to a radiology report that says, “Clinical correlation is advised.” That phrase leads neurologists to compare neuroimaging to the clinical phenotype and ask whether the imaging findings make sense. “A VOUS is no different from this,” he said. Neurologists cannot explain all genetic variants, just as neurologists cannot explain all of the spots on a brain scan. “We have to get comfortable with the fact that we do not have answers for everything and that there will be some ambiguities when we are done.”
Genetics is logical and straightforward, and educational sessions are available at conferences for neurologists who are interested in learning more about genetic testing, Dr. Jinnah said. Neurologists also can refer patients to experts. “This referral must be a collaboration,” he said. “People in human genetics are not trained in movement disorders, and many of them have no formal training in neurology. They need your careful phenotypic exam to point them in th
Genetic testing often is expensive, not readily available, and not covered by insurance, but this situation may change, Dr. Jinnah said. He likened the situation of genetic testing today to that of MRI in the 1980s. “Only a few centers in the world had [MRI]. It was extremely expensive. Now, MRI scanners are everywhere, and everybody uses it because it is so valuable in clinical medicine,” he said. “I suspect that in a few years, we will see the same with genetic tests.”
—Jake Remaly
Suggested Reading
Charlesworth G, Bhatia KP, Wood NW. The genetics of dystonia: new twists in an old tale. Brain. 2013;136(Pt 7):2017-2037.
Gahl WA, Tifft CJ. The NIH Undiagnosed Diseases Program: lessons learned. JAMA. 2011;305(18):1904-1905.
Olgiati S, Quadri M, Bonifati V. Genetics of movement disorders in the next-generation sequencing era. Mov Disord. 2016;31(4):458-470.
Sawyer SL, Hartley T, Dyment DA, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016;89(3):275-284.
van Egmond ME, Lugtenberg CHA, Brouwer OF, et al. A post hoc study on gene panel analysis for the diagnosis of dystonia. Mov Disord. 2017;32(4):569-575.
Liposomal daunorubicin and cytarabine approved for t-AML, AML-MRC
, the Food and Drug Administration announced on Aug. 3.
Vyxeos is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC, the FDA said in its press release announcing the approval.
“Vyxeos is the first chemotherapy to demonstrate an overall survival advantage over the standard of care in a phase 3 randomized study of older adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes,” Jeffrey E. Lancet, MD, an investigator in the clinical trials of Vyxeos and chair of the department of malignant hematology at the H. Lee Moffitt Cancer Center in Tampa, Fla., said in a press release.
Vyxeos was associated with a median overall survival of 9.6 months and a standard combination of cytarabine and daunorubicin (7+3) was associated with a median survival of 5.9 months in a randomized, multicenter, open-label trial of 309 patients aged 60-75 years with newly-diagnosed t-AML or AML-MRC. Data from the study, which is NCT01696084, was the basis for the drug’s approval.
Vyxeos is a fixed-dose combination with each Vyxeos vial containing 44 mg daunorubicin and 100 mg cytarabine encapsulated together in liposomes. As dosing is based on the daunorubicin component, the corresponding cytarabine dose does not need to be calculated. Daunorubicin dosing is calculated on the basis of body surface area (mg/m2).
For the first induction cycle, the recommended Vyxeos dose is daunorubicin 44 mg/m2 (cytarabine 100 mg/m2) infused intravenously over 90 minutes on days 1, 3, and 5. If a second induction cycle is needed, the same dose is administered on days 1 and 3. The recommended dose of Vyxeos for each cycle of consolidation therapy is daunorubicin 29 mg/m2 (cytarabine 65 mg/m2) liposome via intravenous infusion over 90 minutes on days 1 and 3.
Adverse reactions occurring in at least 25% of treated patients in the clinical trial included hemorrhage, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The prescribing information includes a boxed warning not to substitute Vyxeos with other daunorubicin- or cytarabine-containing products. Full prescribing information is available at: www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf
The maker of Vyxeos is Jazz Pharmaceuticals.
[email protected]
On Twitter @maryjodales
, the Food and Drug Administration announced on Aug. 3.
Vyxeos is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC, the FDA said in its press release announcing the approval.
“Vyxeos is the first chemotherapy to demonstrate an overall survival advantage over the standard of care in a phase 3 randomized study of older adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes,” Jeffrey E. Lancet, MD, an investigator in the clinical trials of Vyxeos and chair of the department of malignant hematology at the H. Lee Moffitt Cancer Center in Tampa, Fla., said in a press release.
Vyxeos was associated with a median overall survival of 9.6 months and a standard combination of cytarabine and daunorubicin (7+3) was associated with a median survival of 5.9 months in a randomized, multicenter, open-label trial of 309 patients aged 60-75 years with newly-diagnosed t-AML or AML-MRC. Data from the study, which is NCT01696084, was the basis for the drug’s approval.
Vyxeos is a fixed-dose combination with each Vyxeos vial containing 44 mg daunorubicin and 100 mg cytarabine encapsulated together in liposomes. As dosing is based on the daunorubicin component, the corresponding cytarabine dose does not need to be calculated. Daunorubicin dosing is calculated on the basis of body surface area (mg/m2).
For the first induction cycle, the recommended Vyxeos dose is daunorubicin 44 mg/m2 (cytarabine 100 mg/m2) infused intravenously over 90 minutes on days 1, 3, and 5. If a second induction cycle is needed, the same dose is administered on days 1 and 3. The recommended dose of Vyxeos for each cycle of consolidation therapy is daunorubicin 29 mg/m2 (cytarabine 65 mg/m2) liposome via intravenous infusion over 90 minutes on days 1 and 3.
Adverse reactions occurring in at least 25% of treated patients in the clinical trial included hemorrhage, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The prescribing information includes a boxed warning not to substitute Vyxeos with other daunorubicin- or cytarabine-containing products. Full prescribing information is available at: www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf
The maker of Vyxeos is Jazz Pharmaceuticals.
[email protected]
On Twitter @maryjodales
, the Food and Drug Administration announced on Aug. 3.
Vyxeos is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC, the FDA said in its press release announcing the approval.
“Vyxeos is the first chemotherapy to demonstrate an overall survival advantage over the standard of care in a phase 3 randomized study of older adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes,” Jeffrey E. Lancet, MD, an investigator in the clinical trials of Vyxeos and chair of the department of malignant hematology at the H. Lee Moffitt Cancer Center in Tampa, Fla., said in a press release.
Vyxeos was associated with a median overall survival of 9.6 months and a standard combination of cytarabine and daunorubicin (7+3) was associated with a median survival of 5.9 months in a randomized, multicenter, open-label trial of 309 patients aged 60-75 years with newly-diagnosed t-AML or AML-MRC. Data from the study, which is NCT01696084, was the basis for the drug’s approval.
Vyxeos is a fixed-dose combination with each Vyxeos vial containing 44 mg daunorubicin and 100 mg cytarabine encapsulated together in liposomes. As dosing is based on the daunorubicin component, the corresponding cytarabine dose does not need to be calculated. Daunorubicin dosing is calculated on the basis of body surface area (mg/m2).
For the first induction cycle, the recommended Vyxeos dose is daunorubicin 44 mg/m2 (cytarabine 100 mg/m2) infused intravenously over 90 minutes on days 1, 3, and 5. If a second induction cycle is needed, the same dose is administered on days 1 and 3. The recommended dose of Vyxeos for each cycle of consolidation therapy is daunorubicin 29 mg/m2 (cytarabine 65 mg/m2) liposome via intravenous infusion over 90 minutes on days 1 and 3.
Adverse reactions occurring in at least 25% of treated patients in the clinical trial included hemorrhage, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.
The prescribing information includes a boxed warning not to substitute Vyxeos with other daunorubicin- or cytarabine-containing products. Full prescribing information is available at: www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf
The maker of Vyxeos is Jazz Pharmaceuticals.
[email protected]
On Twitter @maryjodales
PHM17 session summary: Tools for engaging learners of all levels
NASHVILLE, TENN. – Various instructional tools and techniques can help hospitalists teach medical learners at a variety of levels, according to experts who spoke at Pediatric Hospital Medicine 2017, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Session
Tools for Engaging Learners of All Levels: Multilevel Teaching Techniques & Cognitive Apprenticeship
Presenters
Session summary
Hospitalists are commonly charged with teaching learners at a variety of levels. There are various tools that can be used to accomplish this including multilevel teaching and cognitive apprenticeship.
Multilevel teaching is defined as teaching multiple levels of learners simultaneously. The goal is to maintain engagement without being boring or teaching over any learner’s head. Examples include:
1. Broadening: Change the case to make it more challenging or interesting such as asking what to do if the patient was a different age or had a comorbid condition.
2. Targeting: Target questions at specific team members depending on difficulty such as asking students common causes of bacterial meningitis and asking residents about admission criteria.
3. Novelty: Provide new data such as a recent journal article.
4. Up the Ladder: Ask the same question to all team members, starting with the most junior.
5. Student as Teacher: Ask a senior learner to teach a junior learner.
6. Multi-Answer: Seek multiple answers to one question such as asking each learner to contribute an item to a differential diagnosis.
7. No Right Answer: Ask questions that do not have a single correct answer such as how to approach a difficult conversation.
8. Teaching to the Top: Teach to the level of the most senior learner.
9. Extreme Challenge: Teach at a level above all learners on the team.
Laura Certain, MD, PhD, et al1 found that most trainees feel Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are most effective. No Right Answer, Teaching to the Top, and Extreme Challenge were felt to be least effective.
Another concept for engaging learners at all levels is cognitive apprenticeship, which is an instructional model whereby teachers make explicit their generally tacit cognitive processes. Examples include:
1. Modeling: Actively demonstrate skills such as performing a procedure while verbalizing the steps and thought processes.
2. Couching: Observe learners and provide feedback on their performance.
3. Scaffolding: Inquire about past experiences and provide opportunity for independent activities, while also providing help for activities that are difficult for learners.
4. Articulation: Ask learners to explain their thought processes.
5. Reflection: Prompt students to deliberately consider their strengths and weaknesses.
6. Exploration: Encourage students to set personal learning goals.
Coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
Key takeaways for Pediatric HM
• Multilevel teaching can be used to engage a variety of learners simultaneously. Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are effective methods to achieve this goal.
• Cognitive apprenticeship can be used in clinical teaching to make a tacit cognitive process explicit. Methods such as coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
• Regardless of the method used, teachers should demonstrate interest in the learners’ education and treat them with respect.
Dr. Rogers is assistant professor of pediatrics and Section of Hospital Medicine associate program director, Pediatric Residency Program, at the Medical College of Wisconsin, Milwaukee.
References
1. Certain LK, Guarino AJ, Greenwald JL. Effective multilevel teaching techniques on attending rounds: a pilot survey and systematic review of the literature. Med Teach. 2011;33(12),e644-650. doi: 10.3109/0142159X.2011.610844.
NASHVILLE, TENN. – Various instructional tools and techniques can help hospitalists teach medical learners at a variety of levels, according to experts who spoke at Pediatric Hospital Medicine 2017, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Session
Tools for Engaging Learners of All Levels: Multilevel Teaching Techniques & Cognitive Apprenticeship
Presenters
Session summary
Hospitalists are commonly charged with teaching learners at a variety of levels. There are various tools that can be used to accomplish this including multilevel teaching and cognitive apprenticeship.
Multilevel teaching is defined as teaching multiple levels of learners simultaneously. The goal is to maintain engagement without being boring or teaching over any learner’s head. Examples include:
1. Broadening: Change the case to make it more challenging or interesting such as asking what to do if the patient was a different age or had a comorbid condition.
2. Targeting: Target questions at specific team members depending on difficulty such as asking students common causes of bacterial meningitis and asking residents about admission criteria.
3. Novelty: Provide new data such as a recent journal article.
4. Up the Ladder: Ask the same question to all team members, starting with the most junior.
5. Student as Teacher: Ask a senior learner to teach a junior learner.
6. Multi-Answer: Seek multiple answers to one question such as asking each learner to contribute an item to a differential diagnosis.
7. No Right Answer: Ask questions that do not have a single correct answer such as how to approach a difficult conversation.
8. Teaching to the Top: Teach to the level of the most senior learner.
9. Extreme Challenge: Teach at a level above all learners on the team.
Laura Certain, MD, PhD, et al1 found that most trainees feel Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are most effective. No Right Answer, Teaching to the Top, and Extreme Challenge were felt to be least effective.
Another concept for engaging learners at all levels is cognitive apprenticeship, which is an instructional model whereby teachers make explicit their generally tacit cognitive processes. Examples include:
1. Modeling: Actively demonstrate skills such as performing a procedure while verbalizing the steps and thought processes.
2. Couching: Observe learners and provide feedback on their performance.
3. Scaffolding: Inquire about past experiences and provide opportunity for independent activities, while also providing help for activities that are difficult for learners.
4. Articulation: Ask learners to explain their thought processes.
5. Reflection: Prompt students to deliberately consider their strengths and weaknesses.
6. Exploration: Encourage students to set personal learning goals.
Coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
Key takeaways for Pediatric HM
• Multilevel teaching can be used to engage a variety of learners simultaneously. Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are effective methods to achieve this goal.
• Cognitive apprenticeship can be used in clinical teaching to make a tacit cognitive process explicit. Methods such as coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
• Regardless of the method used, teachers should demonstrate interest in the learners’ education and treat them with respect.
Dr. Rogers is assistant professor of pediatrics and Section of Hospital Medicine associate program director, Pediatric Residency Program, at the Medical College of Wisconsin, Milwaukee.
References
1. Certain LK, Guarino AJ, Greenwald JL. Effective multilevel teaching techniques on attending rounds: a pilot survey and systematic review of the literature. Med Teach. 2011;33(12),e644-650. doi: 10.3109/0142159X.2011.610844.
NASHVILLE, TENN. – Various instructional tools and techniques can help hospitalists teach medical learners at a variety of levels, according to experts who spoke at Pediatric Hospital Medicine 2017, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Session
Tools for Engaging Learners of All Levels: Multilevel Teaching Techniques & Cognitive Apprenticeship
Presenters
Session summary
Hospitalists are commonly charged with teaching learners at a variety of levels. There are various tools that can be used to accomplish this including multilevel teaching and cognitive apprenticeship.
Multilevel teaching is defined as teaching multiple levels of learners simultaneously. The goal is to maintain engagement without being boring or teaching over any learner’s head. Examples include:
1. Broadening: Change the case to make it more challenging or interesting such as asking what to do if the patient was a different age or had a comorbid condition.
2. Targeting: Target questions at specific team members depending on difficulty such as asking students common causes of bacterial meningitis and asking residents about admission criteria.
3. Novelty: Provide new data such as a recent journal article.
4. Up the Ladder: Ask the same question to all team members, starting with the most junior.
5. Student as Teacher: Ask a senior learner to teach a junior learner.
6. Multi-Answer: Seek multiple answers to one question such as asking each learner to contribute an item to a differential diagnosis.
7. No Right Answer: Ask questions that do not have a single correct answer such as how to approach a difficult conversation.
8. Teaching to the Top: Teach to the level of the most senior learner.
9. Extreme Challenge: Teach at a level above all learners on the team.
Laura Certain, MD, PhD, et al1 found that most trainees feel Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are most effective. No Right Answer, Teaching to the Top, and Extreme Challenge were felt to be least effective.
Another concept for engaging learners at all levels is cognitive apprenticeship, which is an instructional model whereby teachers make explicit their generally tacit cognitive processes. Examples include:
1. Modeling: Actively demonstrate skills such as performing a procedure while verbalizing the steps and thought processes.
2. Couching: Observe learners and provide feedback on their performance.
3. Scaffolding: Inquire about past experiences and provide opportunity for independent activities, while also providing help for activities that are difficult for learners.
4. Articulation: Ask learners to explain their thought processes.
5. Reflection: Prompt students to deliberately consider their strengths and weaknesses.
6. Exploration: Encourage students to set personal learning goals.
Coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
Key takeaways for Pediatric HM
• Multilevel teaching can be used to engage a variety of learners simultaneously. Targeting, Up the Ladder, Student as Teacher, and Multi-Answer are effective methods to achieve this goal.
• Cognitive apprenticeship can be used in clinical teaching to make a tacit cognitive process explicit. Methods such as coaching and articulation have been found to be more useful for novice learners. Reflection and exploration are more useful for advanced learners.
• Regardless of the method used, teachers should demonstrate interest in the learners’ education and treat them with respect.
Dr. Rogers is assistant professor of pediatrics and Section of Hospital Medicine associate program director, Pediatric Residency Program, at the Medical College of Wisconsin, Milwaukee.
References
1. Certain LK, Guarino AJ, Greenwald JL. Effective multilevel teaching techniques on attending rounds: a pilot survey and systematic review of the literature. Med Teach. 2011;33(12),e644-650. doi: 10.3109/0142159X.2011.610844.
At PHM 2017
VIDEO: Study highlights risks of postponing cholecystectomy
Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).
“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.
Source: American Gastroenterological Association
Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.
Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).
In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).
Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.
They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).
“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”
Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.
Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).
“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.
Source: American Gastroenterological Association
Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.
Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).
In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).
Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.
They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).
“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”
Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.
Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).
“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.
Source: American Gastroenterological Association
Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.
Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).
In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).
Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.
They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).
“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”
Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy within 60 days.
Major finding: A total of 48% had no cholecystectomy within 60 days. Performing cholecystectomy during index admission cut the risk of recurrent biliary events within 60 days by 92%, compared with delayed or no cholecystectomy (P less than .001).
Data source: A multistate, retrospective study of 4,516 patients hospitalized with choledocholithiasis.
Disclosures: Funders included a Stanford division of gastroenterology and hepatology divisional seed grant and the National Institutes of Health. The investigators had no conflicts of interest.
South African child has suppressed HIV without ART since infancy
A 9-year-old South African child treated with antiretroviral therapy (ART) for HIV infection for 40 weeks as an infant has been living with an undetectable level of the virus ever since without ART, researchers reported on July 24.
“To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” said Avy Violari, MD, at the International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.
Starting with a high viral load at 9 weeks of age, the child’s treatment brought the viral load to undetectable levels and was halted after 40 weeks. Follow-up examinations and blood sampling over the next 8.5 years showed the child in good health, with only a small reservoir of virus in a tiny portion of immune cells, but a completely undetectable viral load by standard assays. The child’s immune system is healthy, and there are no symptoms of HIV infection.
“Further study is needed to learn how to induce long-term HIV remission in infected babies,” Anthony S. Fauci, MD, director of NIAID, said in an NIH news release about the case. “However, this new case strengthens our hope that by treating HIV-infected children for a brief period beginning in infancy, we may be able to spare them the burden of lifelong therapy and the health consequences of long-term immune activation typically associated with HIV disease.”
A 9-year-old South African child treated with antiretroviral therapy (ART) for HIV infection for 40 weeks as an infant has been living with an undetectable level of the virus ever since without ART, researchers reported on July 24.
“To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” said Avy Violari, MD, at the International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.
Starting with a high viral load at 9 weeks of age, the child’s treatment brought the viral load to undetectable levels and was halted after 40 weeks. Follow-up examinations and blood sampling over the next 8.5 years showed the child in good health, with only a small reservoir of virus in a tiny portion of immune cells, but a completely undetectable viral load by standard assays. The child’s immune system is healthy, and there are no symptoms of HIV infection.
“Further study is needed to learn how to induce long-term HIV remission in infected babies,” Anthony S. Fauci, MD, director of NIAID, said in an NIH news release about the case. “However, this new case strengthens our hope that by treating HIV-infected children for a brief period beginning in infancy, we may be able to spare them the burden of lifelong therapy and the health consequences of long-term immune activation typically associated with HIV disease.”
A 9-year-old South African child treated with antiretroviral therapy (ART) for HIV infection for 40 weeks as an infant has been living with an undetectable level of the virus ever since without ART, researchers reported on July 24.
“To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” said Avy Violari, MD, at the International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.
Starting with a high viral load at 9 weeks of age, the child’s treatment brought the viral load to undetectable levels and was halted after 40 weeks. Follow-up examinations and blood sampling over the next 8.5 years showed the child in good health, with only a small reservoir of virus in a tiny portion of immune cells, but a completely undetectable viral load by standard assays. The child’s immune system is healthy, and there are no symptoms of HIV infection.
“Further study is needed to learn how to induce long-term HIV remission in infected babies,” Anthony S. Fauci, MD, director of NIAID, said in an NIH news release about the case. “However, this new case strengthens our hope that by treating HIV-infected children for a brief period beginning in infancy, we may be able to spare them the burden of lifelong therapy and the health consequences of long-term immune activation typically associated with HIV disease.”
FROM IAS 2017
Solid organ transplantation contributes significantly to incidence of NHL among children and adolescents
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
[email protected]
On Twitter @eaztweets
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
[email protected]
On Twitter @eaztweets
Solid organ transplant recipients contribute a disproportionate fraction of pediatric non-Hodgkin lymphoma (NHL) cases, especially diffuse large B-cell lymphoma cases (DLBCL), according to an analysis of data drawn from transplant and cancer registries.
Investigators calculated that the incidence of NHL for the pediatric transplant population was 257 times higher than the general population, after analysis from the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012. The incidence of NHL for the pediatric transplant population was 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general population. Furthermore, transplant recipients made up a much larger proportion of general population DLBCL cases (7.62%; 95% CI, 6.35%-8.88%).
In the general population, the most common subtypes were DLBCL (25% of cases), Burkitt lymphoma (24%), and precursor cell lymphoblastic lymphoma (20%). Among NHLs diagnosed in transplant recipients, 65% were DLBCL, and 9% were Burkitt lymphoma, whereas there were no cases of precursor cell lymphoblastic lymphoma, reported Elizabeth L. Yanik, PhD, of Washington University, St. Louis, and her associates (Cancer. 2017 Jul 31. doi: 10.1002/cncr.30923).
The increased risk of NHL and other cancers for organ transplant recipients is primarily the result of the immunosuppressant medications administered after transplantation, leading to an increased risk of infection-related cancers, the authors said.
“NHL cases are largely attributable to EBV [Epstein-Barr virus] infections that occur while recipients are immunosuppressed, as evidenced by the high prevalence of EBV detectable in NHL tumors and particularly in cases diagnosed during the heavily immunosuppressed period early after transplantation,” wrote Dr. Yanik and her colleagues. “Patients who experience a primary EBV infection after transplantation are particularly susceptible because transplant recipients have a higher NHL risk if they are seronegative for EBV before transplantation.”
Among those at risk, Dr. Yanik and fellow investigators found transplant patients younger than 5 years were the most susceptible to NHL, making up 19.79% of those diagnosed with DLBCL.
The proportion of NHL in solid organ transplant recipients within the entire pediatric NHL population has risen over time, from 1.66% of the NHL population during 1990-1994 to 3.73% during 2010-2012.
“This trend is driven by the rising prevalence of transplant recipients in the general population and not by increases in NHL risk among transplant recipients,” noted Dr. Yanik and her coauthors. “The proportion of NHL diagnoses attributable to transplant recipients has grown over time, and it is likely that this population will be an important source of pediatric NHL cases in the future.”
This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
[email protected]
On Twitter @eaztweets
FROM CANCER
Key clinical point: Solid organ transplant recipients contribute a disproportionate fraction of pediatric NHL cases, especially DLBCL cases.
Major finding: Incidence of NHL among the pediatric transplant population was 257 times higher at 306 cases per 100,000 person-years (95% CI, 271-344), compared to 1.19 cases per 100,000 person-years (95% CI, 1.12-1.27) in the general pediatric population.
Data source: Retrospective cohort study of children and adolescents in the U.S. transplant registry and 16 cancer registries from around the country between 1990 and 2012.
Disclosures: This study was partially funded by the National Cancer Institute. One coauthor reported being an employee at GRAIL Inc. No other relevant financial disclosures were reported.
POLL: Draft classification criteria for SLE stir controversy
[polldaddy:9802068]
[polldaddy:9802068]
[polldaddy:9802068]
Thirdhand smoke shaping up as potential health hazard
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
DENVER – Thirdhand smoke – the persistent residue that collects on indoor surfaces where people have smoked – is “clearly” a potentially hazardous exposure, John M. Rogers, PhD, said at the annual meeting of the Teratology Society.
Everyone knows about the hazards of secondhand smoke, which have led to widespread bans on smoking in public spaces. Still, the Centers for Disease Control and Prevention estimates that 58 million nonsmokers in the United States are exposed to secondhand smoke on a regular basis. And where there is secondhand smoke, there is typically exposure to thirdhand smoke as well.
“If you walk into a hotel room you were told is a nonsmoking room and you take one breath and you know it’s not nonsmoking, that’s thirdhand smoke. Thirdhand smoke is all over the place where smokers have been,” explained Dr. Rogers, director of the toxicity assessment division at the Environmental Protection Agency in Research Triangle Park, N.C.
The main potential health risk is to young children, who ingest thirdhand smoke by the hand-to-mouth route and skin contact.
Thirdhand smoke is a much newer concept than secondhand smoke and has not yet actually been shown to pose a significant health risk. . But that is likely to change.
Thirdhand smoke has become an area of intensive research interest, with California leading the way. The Tobacco-Related Disease Research Program, a state agency funded by a tax on the sale of tobacco products, has created a research consortium on thirdhand smoke, with studies underway investigating thirdhand smoke’s precise chemical composition, cytotoxicity, genotoxicity, and true impact on public health (www.trdrp.org).
Concern regarding thirdhand smoke’s potential public health impact ramped up in response to a study in which investigators at the University of York, England, measured levels of various tobacco-specific nitrosamines, N-nitrosamines, and nicotine in house dust samples from the homes of smokers. The researchers estimated that years of early life exposure to these compounds at the levels they detected could result in one excess case of cancer per 1,000 exposed individuals (Environ Int. 2014 Oct;71:139-47).
In addition to his update on thirdhand smoke, Dr. Rogers also touched on other recent tobacco-related developments, including a determination by the Food and Drug Administration that there has been no decline in tobacco use in the last 5 years in adolescents and young adults. While cigarette smoking by young people decreased, this was offset by a large increase in the use of electronic cigarettes and a smaller rise in the use of hookah tobacco. Indeed, e-cigarette use is now about double that of cigarettes among youth.
Also of concern is evidence of a striking socioeconomic disparity in smoking prevalence: Low-education, low-income Americans have far higher tobacco use rates.
“That’s pretty alarming,” he said. “I think a lot of people in this audience probably don’t see a lot of smoking these days, but it’s still around.”
Dr. Rogers drew attention to updated evidence reviews on the reproductive and developmental effects of smoking contained in the U.S. Surgeon General’s voluminous 2014 report on the health consequences of smoking. The report concluded that there is now sufficient evidence to infer a causal relationship between maternal smoking in pregnancy, ectopic pregnancy, and orofacial clefts. The available evidence is “suggestive but not sufficient” to infer causality between maternal smoking in pregnancy and atrial septal defects, clubfoot, gastroschisis, and attention-deficit/hyperactivity disorder and other disruptive behavior disorders.
Dr. Rogers reported having no financial disclosures related to his presentation, which he noted did not necessarily reflect the views and policies of the EPA.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
New and Noteworthy Information—August 2017
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
LIFSCREEN data support broader cancer screening in Li-Fraumeni syndrome
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.
Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.
Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.
The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.
At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).
Collectively, this amounted to 226.4 person-years of follow-up.
Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.
Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.
Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).
“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”
The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”
FROM JAMA ONCOLOGY
Key clinical point:
Major finding: A total of 23 new primary cancers were diagnosed in 20 patients; more than half were outside the core spectrum of Li-Fraumeni syndrome.
Data source: A preliminary analysis of a phase 3, randomized, controlled trial comparing standard and intensive screening among 107 individuals with Li-Fraumeni syndrome carrying a TP53 mutation (LIFSCREEN trial).
Disclosures: The investigators report having no relevant disclosures. The trial was funded by the French Ligue Contre le Cancer.