User login
Many believe in unproven causes of cancer, survey shows
A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.
In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.
More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.
“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.
“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”
Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.
The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).
The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).
The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.
Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.
Results
Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).
Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.
The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).
In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.
The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.
However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.
“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.
“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”
Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”
A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.
In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.
More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.
“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.
“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”
Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.
The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).
The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).
The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.
Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.
Results
Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).
Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.
The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).
In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.
The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.
However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.
“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.
“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”
Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”
A new survey suggests many people believe certain environmental and lifestyle factors cause cancer even though there is insufficient evidence to support these beliefs.
In a survey of 1330 people in England, more than 40% of respondents said that stress and food additives can cause cancer.
More than a third of participants reported that cancer may result from exposure to electromagnetic frequencies and eating genetically modified foods.
“It’s worrying to see so many people endorse risk factors for which there is no convincing evidence,” said Samuel Smith, PhD, of the University of Leeds in the UK.
“Compared to past research, it appears the number of people believing in unproven causes of cancer has increased since the start of the century, which could be a result of changes to how we access news and information through the Internet and social media.”
Dr Smith and his colleagues reported results from the survey in European Journal of Cancer.
The researchers surveyed 1330 people with a mean age of 43.7. Slightly more than half (51.6%) were female, most (84.7%) were white, and most (67%) had post-16 qualifications (education beyond age 16).
The survey included questions about 11 known cancer risk factors, such as being overweight, alcohol consumption, having a relative with cancer, and infection with human papillomavirus (HPV).
The survey also included questions about 12 factors that are commonly believed to cause cancer but for which there is no scientific evidence to confirm the belief. Some of these include eating food containing artificial sweeteners and using mobile phones, cleaning products, and aerosol containers.
Respondents were asked how much they agree that each of the factors increase the risk of cancer. Response options were: strongly disagree, disagree, unsure, agree, and strongly agree.
Results
Participants provided a correct response to more of the questions about proven cancer risk factors than unproven factors—53% and 36%, respectively (P<0.01).
Most respondents knew that active smoking (88%) and exposure to smoking (80%) can cause cancer. However, only 30% of them knew that HPV or low fruit and vegetable consumption are proven cancer risk factors.
The most common unproven factors believed to cause cancer were stress (43%), food additives (42%), electromagnetic frequencies (35%), and genetically modified foods (34%).
In addition, 19% of respondents said using microwave ovens can cause cancer, and 15% said drinking from plastic bottles can cause cancer.
The researchers did note that belief in unproven causes of cancer did not mean a person was more likely to have risky lifestyle habits.
However, respondents who had better knowledge of proven causes were more likely to engage in habits that might reduce their risk of cancer.
“People’s beliefs are so important because they have an impact on the lifestyle choices they make,” said Lion Shahab, PhD, of University College London in the UK.
“Those with better awareness of proven causes of cancer were more likely not to smoke and to eat more fruit and vegetables.”
Dr Smith added, “It’s vital to improve public education about the causes of cancer if we want to help people make informed decisions about their lives and ensure they aren’t worrying unnecessarily.”
Abstract: Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Hay, A.D., et al, JAMA 318(8):721, August 22, 2017
BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.
METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).
RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).
CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references ([email protected] – no reprints)
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Hay, A.D., et al, JAMA 318(8):721, August 22, 2017
BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.
METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).
RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).
CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references ([email protected] – no reprints)
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Hay, A.D., et al, JAMA 318(8):721, August 22, 2017
BACKGROUND: Although symptoms and underlying bronchial hyperresponsiveness are similar in asthma and acute lower respiratory tract infection, guidelines do not include recommendations, and evidence is scarce, regarding the use of corticosteroids for acute lower respiratory infections.
METHODS: In this multinational trial, 401 patients (mean age, 47.4 years) without a history of asthma who presented to primary care with suspected acute lower respiratory tract infection were randomized to a five-day course of oral prednisolone (40mg daily) or placebo. Study participants were followed for 28 days for the primary outcomes of the duration of moderately bad or worse cough, and mean symptom severity score on days two to four (score range 0 to 6, for the main symptoms of cough, phlegm production, shortness of breath, sleep disturbance, feeling unwell and activity disturbance).
RESULTS: In both groups, the median duration of moderately bad or worse cough was five days (hazard ratio 1.11, p=NS). On days two to four, the mean symptom severity score was 1.99 points in the prednisolone group vs. 2.16 points in placebo-treated controls (adjusted difference 0.20 point, p=0.05). Absence of a statistically significant difference between the groups persisted in sensitivity and subgroup analyses. Both groups were similar in terms of symptom duration, antibiotic use, patient satisfaction and the nature of adverse events (no serious adverse events occurred).
CONCLUSIONS: This study does not support the use of oral corticosteroids in primary care patients without asthma who present with acute lower respiratory tract infection. 35 references ([email protected] – no reprints)
Learn more about the Primary Care Medical Abstracts and podcasts, for which you can earn up to 9 CME credits per month.
Copyright © The Center for Medical Education
VIDEO: National suicide hotline could result from pending U.S. law
WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.
“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”
The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.
Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.
“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented.
Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.
Dr. Hogan had no disclosures.
WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.
“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”
The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.
Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.
“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented.
Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.
Dr. Hogan had no disclosures.
WASHINGTON – A bill working its way through the U.S. Congress that would mandate study of the feasibility of a three-digit phone number for suicide prevention and mental health crisis has the potential to establish not only a much-needed national hotline, but more broadly “reboot U.S. crisis care,” Michael F. Hogan, PhD, said at the annual conference of the American Association of Suicidology.
“If we get this legislation passed and some funding, it is a remarkable opportunity to get it right,” said Dr. Hogan, a mental health policy consultant based in Delmar, N.Y., and former commissioner of the New York State Office of Mental Health. A single, “N11,” three-digit phone number for suicide prevention, substance abuse, and mental health crises would “provide a skeleton for a whole new system of crisis centers.”
The pending legislation, the National Suicide Hotline Improvement Act of 2017, “would create parity between brain health and heart health,” Dr. Hogan noted in a video interview. The bill passed the Senate in November 2017, and in late March 2018 had a positive hearing before the Energy and Commerce Committee of the House of Representatives. “The prospects are pretty good,” he said.
Currently, U.S. services are “a mess,” bemoaned Dr. Hogan, who attributed the problem to abandonment of a national program starting in 1981 because of funding changes introduced by the Reagan administration. The centerpiece of the current U.S. system, the National Suicide Prevention Lifeline, receives limited and indirect federal support and relies on coordination among more than 160 local crisis line operations across the country that get no federal funding. Many calls into the Lifeline are, by necessity, answered outside of the locality or even the state from where the call was placed. Inadequacies in the resources available to help people who are suicidal or having other mental health crises have placed the response burden on police departments and emergency departments, “the worst place to go” for mental health care, Dr. Hogan said.
“The primary way around the country to address the problem is cops and EDs; that’s expensive and bad. When you don’t have good crisis services, people go to emergency departments where it’s ‘go upstairs or go home,’ ” he lamented.
Establishment of a centralized and funded U.S. crisis call system would tie into other measures aimed at transforming national crisis services called for by the Crisis Now program of the National Association of State Mental Health Program Directors, Dr. Hogan said.
Dr. Hogan had no disclosures.
REPORTING FROM THE AAS ANNUAL CONFERENCE
Bipolar and seizure medication linked with serious immune system reaction
The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.
This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.
Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.
The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.
The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.
HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.
Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.
The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.
This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.
Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.
The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.
The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.
HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.
Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.
The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
The Food and Drug Administration has issued a warning that the seizure and bipolar medication Lamictal (lamotrigine) can cause a rare but potentially life-threatening immune response.
This life-threatening immune response, known as hemophagocytic lymphohistiocytosis (HLH), causes an uncontrolled immune response and can present as a persistent fever greater than 101° F. HLH can also lead to severe issues with blood cells and organs like the liver, kidneys, and lungs.
Lamotrigine is commonly used as a maintenance treatment for patients with bipolar disorder to help manage depression and mood episodes of mania and hypomania. Patients who abruptly stop taking lamotrigine before talking to their physician can suffer seizures, as well as new or worsening mental health issues.
The FDA is recommending that health care providers be aware of the connection between lamotrigine and HLH and be able to recognize and treat the immune response promptly to improve outcomes and decrease mortality. This can be difficult because of the nonspecific nature of HLH symptoms like fever and rash. HLH is commonly confused with another immune-related reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients should be evaluated if they develop fever or rash and immediately discontinue use of lamotrigine if HLH is suspected.
The basis for the new warning is eight cases worldwide of confirmed or suspected HLH involving “reasonable evidence that lamotrigine was the cause of HLH ... based on the timing of events and the order in which they occurred,” the agency said, noting that this number includes only reports submitted to the FDA and found in the medical literature during the 24-year approval history of the drug, so there are likely additional cases about which we are unaware. The eight patients were all hospitalized and received drug and other medical treatments, with one dying.
HLH can be diagnosed if a patient has at least five of the following eight signs or symptoms: fever and rash; enlarged spleen; cytopenias; elevated blood triglycerides and high levels of ferritin or low levels of fibrinogen; hemophagocytosis confirmed via bone marrow, spleen, or lymph node biopsy; decreased or absent natural killer (NK) cell activity; and elevated levels of CD25 in the blood.
Other signs and symptoms may include: enlarged liver, swollen lymph nodes, yellowing of the skin or eyes, unusual bleeding, disturbances in vision, and trouble walking.
The FDA encourages health care providers and patients to report adverse events to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Prolactin, the pituitary, and pregnancy: Where’s the balance?
CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.
The first step: restoring fertility
“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.
Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.
“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.
Preferable to any of these, though, is achieving normal prolactin levels.
In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.
“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).
From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.
Dopamine agonists and pregnancy
Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.
Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.
“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.
Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.
Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.
Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).
“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.
What if the tumor grows in pregnancy?
During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.
The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.
It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.
Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.
“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.
Postpartum prolactinoma considerations
Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.
For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.
Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.
SOURCE: Molitch M ENDO 2018. Abstract M02-2.
CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.
The first step: restoring fertility
“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.
Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.
“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.
Preferable to any of these, though, is achieving normal prolactin levels.
In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.
“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).
From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.
Dopamine agonists and pregnancy
Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.
Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.
“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.
Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.
Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.
Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).
“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.
What if the tumor grows in pregnancy?
During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.
The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.
It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.
Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.
“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.
Postpartum prolactinoma considerations
Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.
For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.
Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.
SOURCE: Molitch M ENDO 2018. Abstract M02-2.
CHICAGO – Management of fertility and reproduction for women with prolactin-secreting pituitary tumors is a balancing act, often in the absence of robust data to support clinical decision making. So judgment, communication, and paying attention to the patient become paramount considerations, said endocrinologist Mark Molitch, MD, speaking at the annual meeting of the Endocrine Society.
The first step: restoring fertility
“Remember that our patients that have hyperprolactinemia are generally infertile,” said Dr. Molitch, Martha Leland Sherwin Professor of Medicine at Northwestern University, Chicago. “You really need to restore prolactin levels to close to normal, or normal, to allow ovulation to occur,” he said.
Dr. Molitch noted that up to 94% of women with hyperprolactinemia will initially have anovulation, amenorrhea, and infertility, but restoration of normal prolactin levels usually corrects these.
“If you have a patient where you are unable to restore prolactin levels to normal, there are other methods” to consider. Patients may end up using clomiphene, gonadotropin-releasing hormone (GnRH) or gonadotropins, or even moving to in vitro fertilization in these cases, said Dr. Molitch.
Preferable to any of these, though, is achieving normal prolactin levels.
In patients who are hyperprolactinemic, “the major action is occurring at the hypothalamic level,” with decreases in pulsatile secretion of GnRH, said Dr. Molitch. Next, there are resultant decreases in gonadotropin secretion, which in turn interrupt the ovary’s normal physiology. “There’s also an interruption in positive estrogen feedback in this cycle,” he said.
“So what’s new in this area is kisspeptin,” Dr. Molitch said, adding that the peptide activates the G-protein coupled receptor GPR54, found in the hypothalamus and pituitary. Infusion of kisspeptin stimulates secretion of luteinizing hormone, follicle stimulating hormone, and testosterone. Conversely, mutations that inactivate GPR43 result in hypogonadotropic hypogonadism, while activating mutations are associated with centrally caused precocious puberty (Biol Reprod. 2011 Oct;85[4]:650-60; Mol Cell Endocrinol. 2011 Oct 22;346[1-2]:29-3).
From this and other work, endocrinologists now know that kisspeptin is “very likely involved in puberty initiation and in response to fasting,” said Dr. Molitch. It’s now thought that high prolactin levels alter kisspeptin levels, “which then causes the further downstream effects,” said Dr. Molitch.
Dopamine agonists and pregnancy
Dopamine agonists are the primary therapies used for patients with prolactinomas and hyperprolactinemia. In patients seeking fertility, the dopamine agonist is usually continued just through the first few weeks of pregnancy, until the patient misses her first menstrual period, he said.
Establishing the menstrual interval is key to knowing when to stop the dopamine agonist, though. “We often use barrier contraceptives, so we can tell what the menstrual interval is – so we can tell when somebody’s missed her period,” Dr. Molitch explained.
“Most of the safety data on these drugs … are based on that relatively short period of exposure,” said Dr. Molitch. “As far as long-term use during pregnancy, only about 100 patients who took bromocriptine throughout pregnancy have been reported,” with two minor fetal anomalies reported from this series of patients, he said.
Though fewer than 20 cases have been reported of cabergoline being continued throughout a pregnancy, “there have not been any problems with that,” said Dr. Molitch.
Overall, over 6,000 pregnancies with bromocriptine exposure, as well as over 1,000 with cabergoline, have now been reported.
Dr. Molitch summarized the aggregate safety data for each dopamine agonist: “When we look at the adverse outcomes that occurred with either of these drugs, as far as spontaneous abortions or terminations, premature deliveries, multiple births, and, of course, the most important thing here being major malformations … in neither drug is there an increase in these adverse outcomes” (J Endocrinol Invest. 2018 Jan;41[1]:129-41).
“In my own mind now, I think that the number of cases with cabergoline now is quite sufficient to justify the safety of its use during pregnancy,” Dr. Molitch said. “However, this is sort of an individualized decision between you – the clinician – as well as your patient to make”: whether to trust the 1,000-case–strong data for cabergoline. “I no longer change patients from cabergoline to bromocriptine because of safety concerns. I think that cabergoline is perfectly safe,” he added.
What if the tumor grows in pregnancy?
During pregnancy, high estrogen levels from the placenta can stimulate prolactinoma growth, and the dopamine agonist’s inhibitory effect is gone once that medication’s been stopped. This means that “We have both a ‘push’ and a decrease in the ‘pull’ here, so you may have tumor enlargement,” said Dr. Molitch.
The risk for tumor enlargement in microadenomas is about 2.4%, and ranges to about 16% for enlargement of macroadenomas during pregnancy. For macroadenomas, “you might consider a prepregnancy debulking of the tumor,” Dr. Molitch said.
It’s reasonable to stop a dopamine agonist once pregnancy’s been established in a patient with a prolactinoma, and “follow the patient symptomatically every few months,” letting suspicious new symptoms like visual changes or headaches be the prompt for visual field exam and magnetic resonance imaging without contrast, said Dr. Molitch.
Though it’s not FDA approved, consideration can be given to continuing a dopamine agonist in a patient with a large prepregnancy adenoma throughout pregnancy – and if the tumor is enlarging significantly, the dopamine agonist should be restarted if it’s been withheld, said Dr. Molitch. Finally, surgery is the option if an enlarging tumor doesn’t respond to a dopamine agonist, unless the pregnancy is far enough along that delivery is a safe option.
“It’s important to actually document that there’s tumor enlargement, because if you’re going to do something like restarting a drug or even surgery, you really want to make sure that it’s the enlarging tumor that’s causing the problem,” said Dr. Molitch.
Postpartum prolactinoma considerations
Postpartum, even though prolactin secretion is upped by nursing, “there are no data to show that lactation stimulates tumor growth,” said Dr. Molitch. “I don’t see that there’s any problem with somebody nursing if they choose to do so.” However, “You certainly cannot restart the dopamine agonist, because that will lower prolactin levels and prevent that person from being able to nurse,” he said.
For reasons that are not clear, prolactin levels often drop post partum. Accordingly, it’s a reasonable approach in a nursing mother with mildly elevated prolactin levels to wait until nursing is done to see if menses resume spontaneously before restarting the dopamine agonist, said Dr. Molitch.
Dr. Molitch reported receiving fees and research funding from several pharmaceutical companies. He also disclosed that his spouse holds stock in Amgen.
SOURCE: Molitch M ENDO 2018. Abstract M02-2.
REPORTING FROM ENDO 2018
Improving survival in older AML patients
The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, Have we begun to witness an improvement in the survival of these patients?
Several clinical trials and observational registration studies have made it very clear that, without treatment, the survival in AML is very short – ranging from 11-16 weeks (for patients enrolled in therapeutic trials who received best supportive care only) to only 6-8 weeks in the “real-world” setting, based upon observational studies.1,2,3,4
These data are very meaningful because older AML patients often do not receive active therapy. As recently as 2009, SEER data indicate that 50% of patients aged 65 years or older receive no treatment for AML. This trend appears to be changing, based upon data from the AMLSG in 2012-2014, in which only a minority of patients in this age range received best supportive care only for their AML.
Knowing the very poor outcomes of patients who are not treated for AML, along with a high number of patients who are not treated, we must next ask whether any treatment at all is superior to no treatment. The data appear relatively clear on this question, with two representative publications highlighting the superiority of treatment vs. no treatment. First, in the SEER registry analysis by Medeiros et al., treated patients had a median survival of 5 months, compared with 2.5 months in untreated patients, and there was an unequivocal survival advantage attributed to treatment after adjustment for covariates and propensity score matching. Treatment included both traditional induction regimens and hypomethylating agent (HMA) therapy. Similarly, a phase 3 clinical trial testing low-dose cytarabine (LDAC) vs. best supportive care demonstrated survival improvement with LDAC (odds ratio, 0.60).
Recognizing that treatment improves survival in older adults with AML and that there is an upward trend in the percent of patients who receive active therapy, we can reasonably ask next whether survival has begun to trend upward over the past several years. This, of course, is a challenging question, but one that can be at least partially addressed through analyses of registration cohorts.
SEER data regarding AML patients aged 65 and older from the 1970s to 2013 suggest modestly improved 2-year survival, from less than 10% in the 1970s to 10%-15% since the early 2000s. The Moffitt Cancer Center database of patients aged 70 years and older also indicates a strong trend toward modestly improved survival after 2005, compared with prior to 2005 (unpublished data). Although the precise reason for trending improvements in overall survival of these patients over time is not clear, it is reasonable to suggest that a greater proportion of patients who receive actual therapy for AML could explain the modest improvements being observed. Improvements in supportive care through the years could also contribute to survival improvement trends over time, though this hypothesis has not been formally tested.
Next, we should ask about the most effective currently available therapy for older adults with AML. Standard treatment options for these patients, as mentioned previously, include high-intensity (traditional induction chemotherapy) and lower-intensity (LDAC, HMAs) regimens. Unfortunately, a prospective, randomized comparison between such regimens has not been undertaken, so it is impossible to declare with any certainty as to the superiority of one approach versus another. Larger database analyses, utilizing multivariate cox regression analyses, have been performed, suggesting that HMAs and intensive therapies perform similarly, such that offering an older adult with AML frontline therapy with a lower-intensity regimen is very reasonable.5
It is quite important to address the possibility that newer therapies in AML are changing the natural history of the disease. First of all, strategies utilizing HMA therapy with 5-azacitidine or decitabine have been widely studied. Unfortunately, a clear and convincing signal of survival benefit of frontline HMA therapy, compared with conventional care regimens (most commonly LDAC) has not been demonstrated, although trends toward a very modest survival advantage favoring HMAs were observed.6,7
Interestingly, in the AZA-AML-001 study, only the subgroup of patients who were preselected to receive best supportive care achieved survival benefit from 5-azacitidine, again suggesting that treatment vs. no treatment is among the most important factors leading to survival improvement in elderly AML.
Other novel agents are coming to the forefront, with the potential to change the natural history of AML in elderly patients. CPX-351 is a liposomal product that encapsulates cytarabine and daunorubicin in a fixed and synergistic molar ratio, thereby allowing delivery of both agents to the leukemic cell in the optimal fashion for cell kill. A recently completed phase 3 trial in older adults with secondary AML demonstrated statistically significant survival improvement with CPX-351 as compared with traditional daunorubicin plus cytarabine induction. A substantial minority of patients on this trial went to allogeneic hematopoietic cell transplant during first remission, and a landmark analysis performed at the time of transplant indicated better survival among patients who had received initial therapy with CPX-351.8
These data suggest that, in selected older adults with secondary AML who are fit enough to receive induction chemotherapy, CPX-351 offers a survival advantage, even among traditionally higher-risk subgroups, including patients with adverse karyotype of above age 70 years. As such, CPX-351 (Vyxeos) received FDA approval as frontline therapy for secondary AML in 2017.
Newer targeted therapies for older adults with AML also appear to hold promise. Glasdegib, an inhibitor of SMO (part of the hedgehog signaling pathway) was recently studied in combination with LDAC versus LDAC alone in a randomized phase 2 trial in older patients considered unfit for intensive induction chemotherapy. In this trial, patients assigned to glasdegib plus LDAC had longer median and overall survival than patients treated with LDAC alone, suggesting a promising novel agent on the horizon.9
Another example of a promising and novel targeted agent for AML is venetoclax, an inhibitor of BCL-2. Encouragingly high response rates and overall survival in phase 2 trials that combined venetoclax with LDAC or HMAs have driven randomized trials to definitively ascertain a survival advantage in older patients considered unfit for intensive therapy.10,11
The question also arises as to whether therapeutic outcomes can be optimized by better selection of currently available therapies for any given. This concept requires development of a decision analysis model that can be used to accurately predict outcomes among older patients with newly diagnosed AML. At Moffitt Cancer Center, such a model is being developed using a systematic review of the literature, followed by validation in a large institutional database. To date, there is the strong initial suggestion that initial therapy selection can be optimized for best outcome, taking into account variables including ECOG performance status, Charlson Comorbidity Index, and cytogenetic risk.12
The goal of improving survival in older adults with AML remains elusive. The decision to treat (regardless of high vs. low intensity) appears critical toward achieving this goal. New therapies such as CPX-351, glasdegib, and venetoclax also hold promise in further improving survival in subgroups of older patients. Finally, development of accurate predictive models to optimize initial therapy will be of critical importance for improving survival in this very heterogeneous disease that afflicts a very heterogeneous group of patients.
Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.
References
1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.
2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.
3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.
4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.
5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.
6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.
7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.
8. Lancet JE et al. Blood 2016 128:906.
9. Cortes JE et al. Blood 2016 128:99.
10. DiNardo CD et al. Blood 2017 130:2628.
11. Wei A et al. Blood 2017 130:890.
12. Extermann M et al. SIOG 2017.
The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, Have we begun to witness an improvement in the survival of these patients?
Several clinical trials and observational registration studies have made it very clear that, without treatment, the survival in AML is very short – ranging from 11-16 weeks (for patients enrolled in therapeutic trials who received best supportive care only) to only 6-8 weeks in the “real-world” setting, based upon observational studies.1,2,3,4
These data are very meaningful because older AML patients often do not receive active therapy. As recently as 2009, SEER data indicate that 50% of patients aged 65 years or older receive no treatment for AML. This trend appears to be changing, based upon data from the AMLSG in 2012-2014, in which only a minority of patients in this age range received best supportive care only for their AML.
Knowing the very poor outcomes of patients who are not treated for AML, along with a high number of patients who are not treated, we must next ask whether any treatment at all is superior to no treatment. The data appear relatively clear on this question, with two representative publications highlighting the superiority of treatment vs. no treatment. First, in the SEER registry analysis by Medeiros et al., treated patients had a median survival of 5 months, compared with 2.5 months in untreated patients, and there was an unequivocal survival advantage attributed to treatment after adjustment for covariates and propensity score matching. Treatment included both traditional induction regimens and hypomethylating agent (HMA) therapy. Similarly, a phase 3 clinical trial testing low-dose cytarabine (LDAC) vs. best supportive care demonstrated survival improvement with LDAC (odds ratio, 0.60).
Recognizing that treatment improves survival in older adults with AML and that there is an upward trend in the percent of patients who receive active therapy, we can reasonably ask next whether survival has begun to trend upward over the past several years. This, of course, is a challenging question, but one that can be at least partially addressed through analyses of registration cohorts.
SEER data regarding AML patients aged 65 and older from the 1970s to 2013 suggest modestly improved 2-year survival, from less than 10% in the 1970s to 10%-15% since the early 2000s. The Moffitt Cancer Center database of patients aged 70 years and older also indicates a strong trend toward modestly improved survival after 2005, compared with prior to 2005 (unpublished data). Although the precise reason for trending improvements in overall survival of these patients over time is not clear, it is reasonable to suggest that a greater proportion of patients who receive actual therapy for AML could explain the modest improvements being observed. Improvements in supportive care through the years could also contribute to survival improvement trends over time, though this hypothesis has not been formally tested.
Next, we should ask about the most effective currently available therapy for older adults with AML. Standard treatment options for these patients, as mentioned previously, include high-intensity (traditional induction chemotherapy) and lower-intensity (LDAC, HMAs) regimens. Unfortunately, a prospective, randomized comparison between such regimens has not been undertaken, so it is impossible to declare with any certainty as to the superiority of one approach versus another. Larger database analyses, utilizing multivariate cox regression analyses, have been performed, suggesting that HMAs and intensive therapies perform similarly, such that offering an older adult with AML frontline therapy with a lower-intensity regimen is very reasonable.5
It is quite important to address the possibility that newer therapies in AML are changing the natural history of the disease. First of all, strategies utilizing HMA therapy with 5-azacitidine or decitabine have been widely studied. Unfortunately, a clear and convincing signal of survival benefit of frontline HMA therapy, compared with conventional care regimens (most commonly LDAC) has not been demonstrated, although trends toward a very modest survival advantage favoring HMAs were observed.6,7
Interestingly, in the AZA-AML-001 study, only the subgroup of patients who were preselected to receive best supportive care achieved survival benefit from 5-azacitidine, again suggesting that treatment vs. no treatment is among the most important factors leading to survival improvement in elderly AML.
Other novel agents are coming to the forefront, with the potential to change the natural history of AML in elderly patients. CPX-351 is a liposomal product that encapsulates cytarabine and daunorubicin in a fixed and synergistic molar ratio, thereby allowing delivery of both agents to the leukemic cell in the optimal fashion for cell kill. A recently completed phase 3 trial in older adults with secondary AML demonstrated statistically significant survival improvement with CPX-351 as compared with traditional daunorubicin plus cytarabine induction. A substantial minority of patients on this trial went to allogeneic hematopoietic cell transplant during first remission, and a landmark analysis performed at the time of transplant indicated better survival among patients who had received initial therapy with CPX-351.8
These data suggest that, in selected older adults with secondary AML who are fit enough to receive induction chemotherapy, CPX-351 offers a survival advantage, even among traditionally higher-risk subgroups, including patients with adverse karyotype of above age 70 years. As such, CPX-351 (Vyxeos) received FDA approval as frontline therapy for secondary AML in 2017.
Newer targeted therapies for older adults with AML also appear to hold promise. Glasdegib, an inhibitor of SMO (part of the hedgehog signaling pathway) was recently studied in combination with LDAC versus LDAC alone in a randomized phase 2 trial in older patients considered unfit for intensive induction chemotherapy. In this trial, patients assigned to glasdegib plus LDAC had longer median and overall survival than patients treated with LDAC alone, suggesting a promising novel agent on the horizon.9
Another example of a promising and novel targeted agent for AML is venetoclax, an inhibitor of BCL-2. Encouragingly high response rates and overall survival in phase 2 trials that combined venetoclax with LDAC or HMAs have driven randomized trials to definitively ascertain a survival advantage in older patients considered unfit for intensive therapy.10,11
The question also arises as to whether therapeutic outcomes can be optimized by better selection of currently available therapies for any given. This concept requires development of a decision analysis model that can be used to accurately predict outcomes among older patients with newly diagnosed AML. At Moffitt Cancer Center, such a model is being developed using a systematic review of the literature, followed by validation in a large institutional database. To date, there is the strong initial suggestion that initial therapy selection can be optimized for best outcome, taking into account variables including ECOG performance status, Charlson Comorbidity Index, and cytogenetic risk.12
The goal of improving survival in older adults with AML remains elusive. The decision to treat (regardless of high vs. low intensity) appears critical toward achieving this goal. New therapies such as CPX-351, glasdegib, and venetoclax also hold promise in further improving survival in subgroups of older patients. Finally, development of accurate predictive models to optimize initial therapy will be of critical importance for improving survival in this very heterogeneous disease that afflicts a very heterogeneous group of patients.
Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.
References
1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.
2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.
3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.
4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.
5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.
6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.
7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.
8. Lancet JE et al. Blood 2016 128:906.
9. Cortes JE et al. Blood 2016 128:99.
10. DiNardo CD et al. Blood 2017 130:2628.
11. Wei A et al. Blood 2017 130:890.
12. Extermann M et al. SIOG 2017.
The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, Have we begun to witness an improvement in the survival of these patients?
Several clinical trials and observational registration studies have made it very clear that, without treatment, the survival in AML is very short – ranging from 11-16 weeks (for patients enrolled in therapeutic trials who received best supportive care only) to only 6-8 weeks in the “real-world” setting, based upon observational studies.1,2,3,4
These data are very meaningful because older AML patients often do not receive active therapy. As recently as 2009, SEER data indicate that 50% of patients aged 65 years or older receive no treatment for AML. This trend appears to be changing, based upon data from the AMLSG in 2012-2014, in which only a minority of patients in this age range received best supportive care only for their AML.
Knowing the very poor outcomes of patients who are not treated for AML, along with a high number of patients who are not treated, we must next ask whether any treatment at all is superior to no treatment. The data appear relatively clear on this question, with two representative publications highlighting the superiority of treatment vs. no treatment. First, in the SEER registry analysis by Medeiros et al., treated patients had a median survival of 5 months, compared with 2.5 months in untreated patients, and there was an unequivocal survival advantage attributed to treatment after adjustment for covariates and propensity score matching. Treatment included both traditional induction regimens and hypomethylating agent (HMA) therapy. Similarly, a phase 3 clinical trial testing low-dose cytarabine (LDAC) vs. best supportive care demonstrated survival improvement with LDAC (odds ratio, 0.60).
Recognizing that treatment improves survival in older adults with AML and that there is an upward trend in the percent of patients who receive active therapy, we can reasonably ask next whether survival has begun to trend upward over the past several years. This, of course, is a challenging question, but one that can be at least partially addressed through analyses of registration cohorts.
SEER data regarding AML patients aged 65 and older from the 1970s to 2013 suggest modestly improved 2-year survival, from less than 10% in the 1970s to 10%-15% since the early 2000s. The Moffitt Cancer Center database of patients aged 70 years and older also indicates a strong trend toward modestly improved survival after 2005, compared with prior to 2005 (unpublished data). Although the precise reason for trending improvements in overall survival of these patients over time is not clear, it is reasonable to suggest that a greater proportion of patients who receive actual therapy for AML could explain the modest improvements being observed. Improvements in supportive care through the years could also contribute to survival improvement trends over time, though this hypothesis has not been formally tested.
Next, we should ask about the most effective currently available therapy for older adults with AML. Standard treatment options for these patients, as mentioned previously, include high-intensity (traditional induction chemotherapy) and lower-intensity (LDAC, HMAs) regimens. Unfortunately, a prospective, randomized comparison between such regimens has not been undertaken, so it is impossible to declare with any certainty as to the superiority of one approach versus another. Larger database analyses, utilizing multivariate cox regression analyses, have been performed, suggesting that HMAs and intensive therapies perform similarly, such that offering an older adult with AML frontline therapy with a lower-intensity regimen is very reasonable.5
It is quite important to address the possibility that newer therapies in AML are changing the natural history of the disease. First of all, strategies utilizing HMA therapy with 5-azacitidine or decitabine have been widely studied. Unfortunately, a clear and convincing signal of survival benefit of frontline HMA therapy, compared with conventional care regimens (most commonly LDAC) has not been demonstrated, although trends toward a very modest survival advantage favoring HMAs were observed.6,7
Interestingly, in the AZA-AML-001 study, only the subgroup of patients who were preselected to receive best supportive care achieved survival benefit from 5-azacitidine, again suggesting that treatment vs. no treatment is among the most important factors leading to survival improvement in elderly AML.
Other novel agents are coming to the forefront, with the potential to change the natural history of AML in elderly patients. CPX-351 is a liposomal product that encapsulates cytarabine and daunorubicin in a fixed and synergistic molar ratio, thereby allowing delivery of both agents to the leukemic cell in the optimal fashion for cell kill. A recently completed phase 3 trial in older adults with secondary AML demonstrated statistically significant survival improvement with CPX-351 as compared with traditional daunorubicin plus cytarabine induction. A substantial minority of patients on this trial went to allogeneic hematopoietic cell transplant during first remission, and a landmark analysis performed at the time of transplant indicated better survival among patients who had received initial therapy with CPX-351.8
These data suggest that, in selected older adults with secondary AML who are fit enough to receive induction chemotherapy, CPX-351 offers a survival advantage, even among traditionally higher-risk subgroups, including patients with adverse karyotype of above age 70 years. As such, CPX-351 (Vyxeos) received FDA approval as frontline therapy for secondary AML in 2017.
Newer targeted therapies for older adults with AML also appear to hold promise. Glasdegib, an inhibitor of SMO (part of the hedgehog signaling pathway) was recently studied in combination with LDAC versus LDAC alone in a randomized phase 2 trial in older patients considered unfit for intensive induction chemotherapy. In this trial, patients assigned to glasdegib plus LDAC had longer median and overall survival than patients treated with LDAC alone, suggesting a promising novel agent on the horizon.9
Another example of a promising and novel targeted agent for AML is venetoclax, an inhibitor of BCL-2. Encouragingly high response rates and overall survival in phase 2 trials that combined venetoclax with LDAC or HMAs have driven randomized trials to definitively ascertain a survival advantage in older patients considered unfit for intensive therapy.10,11
The question also arises as to whether therapeutic outcomes can be optimized by better selection of currently available therapies for any given. This concept requires development of a decision analysis model that can be used to accurately predict outcomes among older patients with newly diagnosed AML. At Moffitt Cancer Center, such a model is being developed using a systematic review of the literature, followed by validation in a large institutional database. To date, there is the strong initial suggestion that initial therapy selection can be optimized for best outcome, taking into account variables including ECOG performance status, Charlson Comorbidity Index, and cytogenetic risk.12
The goal of improving survival in older adults with AML remains elusive. The decision to treat (regardless of high vs. low intensity) appears critical toward achieving this goal. New therapies such as CPX-351, glasdegib, and venetoclax also hold promise in further improving survival in subgroups of older patients. Finally, development of accurate predictive models to optimize initial therapy will be of critical importance for improving survival in this very heterogeneous disease that afflicts a very heterogeneous group of patients.
Dr. Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa. He has received consulting fees from Astellas, BioSight, Celgene, Janssen R&D, and Jazz Pharmaceuticals.
References
1. Burnett AK et al. Cancer. 2007 Mar 15;109(6):1114-24.
2. Harousseau JL et al. Blood. 2009 Aug 6;114(6):1166-73.
3. Medeiros BC et al. Ann Hematol. 2015 Mar 20; 94(7):1127-38.
4. Oran B et al. Haematologica. 2012 Dec;97(12):1916-24.
5. Lancet JE et al. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.35.15_suppl.7031.
6. Dombret H et al. Blood. 2015 Jul 16;126(3):291-9.
7. Kantarjian HM et al. J Clin Oncol. 2012 Jul 20;30(21):2670-7.
8. Lancet JE et al. Blood 2016 128:906.
9. Cortes JE et al. Blood 2016 128:99.
10. DiNardo CD et al. Blood 2017 130:2628.
11. Wei A et al. Blood 2017 130:890.
12. Extermann M et al. SIOG 2017.
Continuous EEG Helps Detect Delayed Cerebral Ischemia
Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.
- DCI is a common complication of subarachnoid hemorrhage.
- Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
- Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
- Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.
Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232
Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.
- DCI is a common complication of subarachnoid hemorrhage.
- Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
- Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
- Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.
Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232
Performing continuous EEG (cEEG) monitoring in patients who have experienced a subarachnoid hemorrhage can help predict the occurrence of delayed cerebral ischemia (DCI) according to a prospective study of 103 patients who underwent cEEG.
- DCI is a common complication of subarachnoid hemorrhage.
- Retrospective studies have suggested a link between cEEG and DCI but the association needed to be confirmed with a prospective evaluation.
- Continuous EEG monitoring involved an average of 7.7 days duration, and a EEG alarm occurred in about 96% of patients with subsequent DCI but in only 19.6% of patients without the ischemic complication.
- Among patients who had a EEG alarm, late onset epileptiform abnormalities were most likely to predict DCI.
Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy [published online ahead of print Apr 16, 2018]. Ann Neurol. doi: 10.1002/ana.25232
Measuring Suboptimal Effort in Adults with Epilepsy
The commonly accepted cutoff scores for reliable digit span (RDS), a way to measure attention and working memory and assess suboptimal effort, are not appropriate for adults with epilepsy, according to a study of 63 patients with epilepsy or suspected seizures.
- A cutoff of ≤6 or ≤7 for RDS, which is part of the Wechsler Adult Intelligence Scale, is typically used in adult clinical populations.
- Maiman et al applied these thresholds to adult patients with epilepsy or suspected seizures, most of whom passed trial 2 of the Test for Memory Malingering with a score of 45 or above.
- A cutoff of 6 or less on the RDS subtest yielded a specificity of 85% while 7 or less yielded 77%.
- A secondary analysis concluded that a cutoff of 4 or less may be more appropriate for adults with epilepsy who have a low average IQ or lower.
Maiman M, Del Bene VA, MacAllister WS, et al. Reliable digit span: does it adequately measure suboptimal effort in an adult epilepsy population [published online ahead of print April 5, 2018]? Arch Clin Neuropsychol. doi: 10.1093/arclin/acy027
The commonly accepted cutoff scores for reliable digit span (RDS), a way to measure attention and working memory and assess suboptimal effort, are not appropriate for adults with epilepsy, according to a study of 63 patients with epilepsy or suspected seizures.
- A cutoff of ≤6 or ≤7 for RDS, which is part of the Wechsler Adult Intelligence Scale, is typically used in adult clinical populations.
- Maiman et al applied these thresholds to adult patients with epilepsy or suspected seizures, most of whom passed trial 2 of the Test for Memory Malingering with a score of 45 or above.
- A cutoff of 6 or less on the RDS subtest yielded a specificity of 85% while 7 or less yielded 77%.
- A secondary analysis concluded that a cutoff of 4 or less may be more appropriate for adults with epilepsy who have a low average IQ or lower.
Maiman M, Del Bene VA, MacAllister WS, et al. Reliable digit span: does it adequately measure suboptimal effort in an adult epilepsy population [published online ahead of print April 5, 2018]? Arch Clin Neuropsychol. doi: 10.1093/arclin/acy027
The commonly accepted cutoff scores for reliable digit span (RDS), a way to measure attention and working memory and assess suboptimal effort, are not appropriate for adults with epilepsy, according to a study of 63 patients with epilepsy or suspected seizures.
- A cutoff of ≤6 or ≤7 for RDS, which is part of the Wechsler Adult Intelligence Scale, is typically used in adult clinical populations.
- Maiman et al applied these thresholds to adult patients with epilepsy or suspected seizures, most of whom passed trial 2 of the Test for Memory Malingering with a score of 45 or above.
- A cutoff of 6 or less on the RDS subtest yielded a specificity of 85% while 7 or less yielded 77%.
- A secondary analysis concluded that a cutoff of 4 or less may be more appropriate for adults with epilepsy who have a low average IQ or lower.
Maiman M, Del Bene VA, MacAllister WS, et al. Reliable digit span: does it adequately measure suboptimal effort in an adult epilepsy population [published online ahead of print April 5, 2018]? Arch Clin Neuropsychol. doi: 10.1093/arclin/acy027
International travel updates
It’s that time of year again. Many of your patients will join the 80.2 million Americans with plans for international travel this summer.
In 2016, Mexico (31.2 million) and Canada (13.9 million) were the top two destinations of U.S. residents. Based on 2016 U.S. Commerce data, an additional 35.1 million Americans headed to overseas destinations, including 9% who traveled with children. Vacation and visiting friends and relatives accounted for 55% and 27% of the reasons for all travel, respectively. Education accounted for 4% of travelers.
Required versus recommended vaccines
The goal of a required vaccine is to prevent international spread of disease. The host country is protecting its citizens from visitors importing and facilitating the spread of a disease. Yellow fever and meningococcal disease are the only vaccines required for entry into any country. Entry requirements vary by country. Yellow fever may be an entry requirement for all travelers or it may be limited to those who have been in, or have had transit through, a country where yellow fever can be transmitted at least 6 days prior to the arrival at their final destination – a reminder that the sequence of the patient’s itinerary is important. In addition, just because a vaccine is not required for entry does not mean the risk for exposure and acquisition is nonexistent.
In contrast, recommended vaccines are for the protection of the individual. Travelers may be exposed to vaccine-preventable diseases that do not exist in their country (such as measles, typhoid fever, and yellow fever). They are at risk for acquisition and may return home infected, which could create the potential to spread the disease to susceptible contacts.
Most travelers comprehend required vaccines but often fail to understand the importance of receiving recommended vaccines. Lammert et al. reported that, of 24,478 persons who received pretravel advice between July 2012 and June 2014 through Global TravEpiNet, a national consortium of U.S. clinics, 97% were eligible for at least one vaccine. The majority were eligible for typhoid (n = 20,092) and hepatitis A (n = 12,990). Of patients included in the study, 25% (6,573) refused one or more vaccines. The most common reason cited for refusal was a lack of concern about the illness. Travelers visiting friends and relatives were less likely to accept all recommended vaccines, compared with those who were not visiting friends and relatives (odds ratio, 0.74) (J Trav Med. 2017 Jan. doi: 10.1093/jtm/taw075). In the United States, international travel remains the most common risk factor for acquisition of both typhoid fever and hepatitis A.
What’s new
The U.S. Advisory Committee on Immunization Practices recommends administering the hepatitis A vaccine to infants aged 6-11 months with travel to or living in developing countries and areas with high to moderate risk for hepatitis A virus transmission. Any dose received at less than 12 months of age does not count, and the administration of two age-appropriate doses should occur following this dose.
Old but still relevant
Measles: The Advisory Committee on Immunization Practices recommends all infants aged 6-11 months receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Prior to administering, determine whether your patient will travel to a yellow fever–endemic area because both are live vaccines and should be received the same day. Otherwise, administer MMR doses 28 days apart; coordination between facilities or receipt of both at one facility may be necessary.
Yellow fever vaccine: The U.S. supplies of YF-Vax by Sanofi Pasteur are not expected to be available again until the end of 2018. To provide vaccines for U.S. travelers, Stamaril – a yellow fever vaccine produced by Sanofi Pasteur in France – has been made available at more than 250 sites through an Expanded Access Investigational New Drug Program.
Since Stamaril is offered at a limited number of locations, persons with anticipated travel to a country where receipt of yellow fever vaccine is either required for entry or recommended for their protection should not wait until the last minute to obtain it. Postponing a trip or changing a destination is preferred if vaccine is not received, especially when the person is traveling to countries with an ongoing outbreak.
The vaccination does not become valid until 10 days after receipt. Infants aged at least 9 months may receive the vaccine. Since the yellow fever vaccine is a live vaccine, administration may be contraindicated in certain individuals. Exemption letters are provided for those with medical contraindication.
To locate a Stamaril site in your area: https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
Current disease outbreaks
Yellow fever: Brazil
Since Dec. 2017, more than 1,100 laboratory-confirmed cases of yellow fever have been reported, including 17 reported in unvaccinated international travelers. Fatal cases also have been reported. In addition to areas in Brazil where yellow fever vaccination had been recommended prior to the recent outbreaks, the vaccine now also is recommended for people who are traveling to or living in all of Espírito Santo State, São Paulo State, and Rio de Janeiro State, as well as several cities in Bahia State. Unvaccinated travelers should avoid travel to areas where vaccination is recommended. Those previously vaccinated at 10 years ago or longer should consider a booster.
Listeria: South Africa
An ongoing outbreak has been reported since Jan. 2017. Around 1,000 people have been infected. Avoid consumption of processed meats including “Polony” (South African bologna).
Measles: Belarus, Japan, Liberia, and Taiwan
All countries have reported an increase in cases since April 2018. Measles outbreaks have been reported in an additional 13 countries since Jan. 2018, including France, Ireland, Italy, the Philippines, and the United Kingdom.
Norovirus: Canada
More than 120 cases have been linked to consumption of raw or lightly cooked oysters from western Canada.
For more country-specific information and up to date travel alerts, visit http://www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and the director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
It’s that time of year again. Many of your patients will join the 80.2 million Americans with plans for international travel this summer.
In 2016, Mexico (31.2 million) and Canada (13.9 million) were the top two destinations of U.S. residents. Based on 2016 U.S. Commerce data, an additional 35.1 million Americans headed to overseas destinations, including 9% who traveled with children. Vacation and visiting friends and relatives accounted for 55% and 27% of the reasons for all travel, respectively. Education accounted for 4% of travelers.
Required versus recommended vaccines
The goal of a required vaccine is to prevent international spread of disease. The host country is protecting its citizens from visitors importing and facilitating the spread of a disease. Yellow fever and meningococcal disease are the only vaccines required for entry into any country. Entry requirements vary by country. Yellow fever may be an entry requirement for all travelers or it may be limited to those who have been in, or have had transit through, a country where yellow fever can be transmitted at least 6 days prior to the arrival at their final destination – a reminder that the sequence of the patient’s itinerary is important. In addition, just because a vaccine is not required for entry does not mean the risk for exposure and acquisition is nonexistent.
In contrast, recommended vaccines are for the protection of the individual. Travelers may be exposed to vaccine-preventable diseases that do not exist in their country (such as measles, typhoid fever, and yellow fever). They are at risk for acquisition and may return home infected, which could create the potential to spread the disease to susceptible contacts.
Most travelers comprehend required vaccines but often fail to understand the importance of receiving recommended vaccines. Lammert et al. reported that, of 24,478 persons who received pretravel advice between July 2012 and June 2014 through Global TravEpiNet, a national consortium of U.S. clinics, 97% were eligible for at least one vaccine. The majority were eligible for typhoid (n = 20,092) and hepatitis A (n = 12,990). Of patients included in the study, 25% (6,573) refused one or more vaccines. The most common reason cited for refusal was a lack of concern about the illness. Travelers visiting friends and relatives were less likely to accept all recommended vaccines, compared with those who were not visiting friends and relatives (odds ratio, 0.74) (J Trav Med. 2017 Jan. doi: 10.1093/jtm/taw075). In the United States, international travel remains the most common risk factor for acquisition of both typhoid fever and hepatitis A.
What’s new
The U.S. Advisory Committee on Immunization Practices recommends administering the hepatitis A vaccine to infants aged 6-11 months with travel to or living in developing countries and areas with high to moderate risk for hepatitis A virus transmission. Any dose received at less than 12 months of age does not count, and the administration of two age-appropriate doses should occur following this dose.
Old but still relevant
Measles: The Advisory Committee on Immunization Practices recommends all infants aged 6-11 months receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Prior to administering, determine whether your patient will travel to a yellow fever–endemic area because both are live vaccines and should be received the same day. Otherwise, administer MMR doses 28 days apart; coordination between facilities or receipt of both at one facility may be necessary.
Yellow fever vaccine: The U.S. supplies of YF-Vax by Sanofi Pasteur are not expected to be available again until the end of 2018. To provide vaccines for U.S. travelers, Stamaril – a yellow fever vaccine produced by Sanofi Pasteur in France – has been made available at more than 250 sites through an Expanded Access Investigational New Drug Program.
Since Stamaril is offered at a limited number of locations, persons with anticipated travel to a country where receipt of yellow fever vaccine is either required for entry or recommended for their protection should not wait until the last minute to obtain it. Postponing a trip or changing a destination is preferred if vaccine is not received, especially when the person is traveling to countries with an ongoing outbreak.
The vaccination does not become valid until 10 days after receipt. Infants aged at least 9 months may receive the vaccine. Since the yellow fever vaccine is a live vaccine, administration may be contraindicated in certain individuals. Exemption letters are provided for those with medical contraindication.
To locate a Stamaril site in your area: https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
Current disease outbreaks
Yellow fever: Brazil
Since Dec. 2017, more than 1,100 laboratory-confirmed cases of yellow fever have been reported, including 17 reported in unvaccinated international travelers. Fatal cases also have been reported. In addition to areas in Brazil where yellow fever vaccination had been recommended prior to the recent outbreaks, the vaccine now also is recommended for people who are traveling to or living in all of Espírito Santo State, São Paulo State, and Rio de Janeiro State, as well as several cities in Bahia State. Unvaccinated travelers should avoid travel to areas where vaccination is recommended. Those previously vaccinated at 10 years ago or longer should consider a booster.
Listeria: South Africa
An ongoing outbreak has been reported since Jan. 2017. Around 1,000 people have been infected. Avoid consumption of processed meats including “Polony” (South African bologna).
Measles: Belarus, Japan, Liberia, and Taiwan
All countries have reported an increase in cases since April 2018. Measles outbreaks have been reported in an additional 13 countries since Jan. 2018, including France, Ireland, Italy, the Philippines, and the United Kingdom.
Norovirus: Canada
More than 120 cases have been linked to consumption of raw or lightly cooked oysters from western Canada.
For more country-specific information and up to date travel alerts, visit http://www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and the director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
It’s that time of year again. Many of your patients will join the 80.2 million Americans with plans for international travel this summer.
In 2016, Mexico (31.2 million) and Canada (13.9 million) were the top two destinations of U.S. residents. Based on 2016 U.S. Commerce data, an additional 35.1 million Americans headed to overseas destinations, including 9% who traveled with children. Vacation and visiting friends and relatives accounted for 55% and 27% of the reasons for all travel, respectively. Education accounted for 4% of travelers.
Required versus recommended vaccines
The goal of a required vaccine is to prevent international spread of disease. The host country is protecting its citizens from visitors importing and facilitating the spread of a disease. Yellow fever and meningococcal disease are the only vaccines required for entry into any country. Entry requirements vary by country. Yellow fever may be an entry requirement for all travelers or it may be limited to those who have been in, or have had transit through, a country where yellow fever can be transmitted at least 6 days prior to the arrival at their final destination – a reminder that the sequence of the patient’s itinerary is important. In addition, just because a vaccine is not required for entry does not mean the risk for exposure and acquisition is nonexistent.
In contrast, recommended vaccines are for the protection of the individual. Travelers may be exposed to vaccine-preventable diseases that do not exist in their country (such as measles, typhoid fever, and yellow fever). They are at risk for acquisition and may return home infected, which could create the potential to spread the disease to susceptible contacts.
Most travelers comprehend required vaccines but often fail to understand the importance of receiving recommended vaccines. Lammert et al. reported that, of 24,478 persons who received pretravel advice between July 2012 and June 2014 through Global TravEpiNet, a national consortium of U.S. clinics, 97% were eligible for at least one vaccine. The majority were eligible for typhoid (n = 20,092) and hepatitis A (n = 12,990). Of patients included in the study, 25% (6,573) refused one or more vaccines. The most common reason cited for refusal was a lack of concern about the illness. Travelers visiting friends and relatives were less likely to accept all recommended vaccines, compared with those who were not visiting friends and relatives (odds ratio, 0.74) (J Trav Med. 2017 Jan. doi: 10.1093/jtm/taw075). In the United States, international travel remains the most common risk factor for acquisition of both typhoid fever and hepatitis A.
What’s new
The U.S. Advisory Committee on Immunization Practices recommends administering the hepatitis A vaccine to infants aged 6-11 months with travel to or living in developing countries and areas with high to moderate risk for hepatitis A virus transmission. Any dose received at less than 12 months of age does not count, and the administration of two age-appropriate doses should occur following this dose.
Old but still relevant
Measles: The Advisory Committee on Immunization Practices recommends all infants aged 6-11 months receive one dose of MMR prior to international travel regardless of the destination. This should be followed by two additional countable doses. All persons at least 12 months of age and born after 1956 should receive two doses of MMR at least 28 days apart prior to international travel.
Prior to administering, determine whether your patient will travel to a yellow fever–endemic area because both are live vaccines and should be received the same day. Otherwise, administer MMR doses 28 days apart; coordination between facilities or receipt of both at one facility may be necessary.
Yellow fever vaccine: The U.S. supplies of YF-Vax by Sanofi Pasteur are not expected to be available again until the end of 2018. To provide vaccines for U.S. travelers, Stamaril – a yellow fever vaccine produced by Sanofi Pasteur in France – has been made available at more than 250 sites through an Expanded Access Investigational New Drug Program.
Since Stamaril is offered at a limited number of locations, persons with anticipated travel to a country where receipt of yellow fever vaccine is either required for entry or recommended for their protection should not wait until the last minute to obtain it. Postponing a trip or changing a destination is preferred if vaccine is not received, especially when the person is traveling to countries with an ongoing outbreak.
The vaccination does not become valid until 10 days after receipt. Infants aged at least 9 months may receive the vaccine. Since the yellow fever vaccine is a live vaccine, administration may be contraindicated in certain individuals. Exemption letters are provided for those with medical contraindication.
To locate a Stamaril site in your area: https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics.
Current disease outbreaks
Yellow fever: Brazil
Since Dec. 2017, more than 1,100 laboratory-confirmed cases of yellow fever have been reported, including 17 reported in unvaccinated international travelers. Fatal cases also have been reported. In addition to areas in Brazil where yellow fever vaccination had been recommended prior to the recent outbreaks, the vaccine now also is recommended for people who are traveling to or living in all of Espírito Santo State, São Paulo State, and Rio de Janeiro State, as well as several cities in Bahia State. Unvaccinated travelers should avoid travel to areas where vaccination is recommended. Those previously vaccinated at 10 years ago or longer should consider a booster.
Listeria: South Africa
An ongoing outbreak has been reported since Jan. 2017. Around 1,000 people have been infected. Avoid consumption of processed meats including “Polony” (South African bologna).
Measles: Belarus, Japan, Liberia, and Taiwan
All countries have reported an increase in cases since April 2018. Measles outbreaks have been reported in an additional 13 countries since Jan. 2018, including France, Ireland, Italy, the Philippines, and the United Kingdom.
Norovirus: Canada
More than 120 cases have been linked to consumption of raw or lightly cooked oysters from western Canada.
For more country-specific information and up to date travel alerts, visit http://www.cdc.gov/travel.
Dr. Word is a pediatric infectious disease specialist and the director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures.
Underserved Hispanic Patients Respond Well to Epilepsy Surgery
Performing epilepsy surgery on underserved Hispanic patients with intractable epilepsy relieves their depression and anxiety and improves their quality of life, according to study of 47 patients between 2008 and 2014.
- Hispanic patients, most of whom were immigrant and Spanish speaking, were treated at a comprehensive epilepsy center in an urban public health setting.
- They underwent presurgical and postsurgical neuropsychological evaluation and were identified retrospectively.
- Medium to large improvements on the Beck Depression Inventory and most quality of care scales were observed postsurgery.
- Less robust effects were also seen on the Beck Anxiety Inventory.
Smith JA, Armacost M, Ensign E, et al. Epilepsy surgery in the underserved Hispanic population improves depression, anxiety, and quality of life. Epilepsy Behav. 2018;83:1-6. https://doi.org/10.1016/j.yebeh.2018.03.015
Performing epilepsy surgery on underserved Hispanic patients with intractable epilepsy relieves their depression and anxiety and improves their quality of life, according to study of 47 patients between 2008 and 2014.
- Hispanic patients, most of whom were immigrant and Spanish speaking, were treated at a comprehensive epilepsy center in an urban public health setting.
- They underwent presurgical and postsurgical neuropsychological evaluation and were identified retrospectively.
- Medium to large improvements on the Beck Depression Inventory and most quality of care scales were observed postsurgery.
- Less robust effects were also seen on the Beck Anxiety Inventory.
Smith JA, Armacost M, Ensign E, et al. Epilepsy surgery in the underserved Hispanic population improves depression, anxiety, and quality of life. Epilepsy Behav. 2018;83:1-6. https://doi.org/10.1016/j.yebeh.2018.03.015
Performing epilepsy surgery on underserved Hispanic patients with intractable epilepsy relieves their depression and anxiety and improves their quality of life, according to study of 47 patients between 2008 and 2014.
- Hispanic patients, most of whom were immigrant and Spanish speaking, were treated at a comprehensive epilepsy center in an urban public health setting.
- They underwent presurgical and postsurgical neuropsychological evaluation and were identified retrospectively.
- Medium to large improvements on the Beck Depression Inventory and most quality of care scales were observed postsurgery.
- Less robust effects were also seen on the Beck Anxiety Inventory.
Smith JA, Armacost M, Ensign E, et al. Epilepsy surgery in the underserved Hispanic population improves depression, anxiety, and quality of life. Epilepsy Behav. 2018;83:1-6. https://doi.org/10.1016/j.yebeh.2018.03.015