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Advanced adenoma on colonoscopy linked to increased colorectal cancer incidence
Advanced adenomas found on diagnostic colonoscopy were associated with increased risk of developing colorectal cancer, while nonadvanced adenomas were not, according to long-term follow-up results from a large screening study.
The findings come from a post hoc analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial that enrolled 154,900 individuals, of whom 15,935 underwent colonoscopy following an abnormal flexible sigmoidoscopy screening result.
With a median of 13 years of follow-up, the incidence of colorectal cancer was 20.0 per 10,000 person-years for patients who had advanced adenoma found on colonoscopy, according to a report on the study published in JAMA. By comparison, colorectal cancer incidence was 9.1 and 7.5 per 10,000 person-years for nonadvanced adenoma and no adenoma, respectively.
“By demonstrating that individuals diagnosed with an advanced adenoma are at increased long-term risk for subsequent incident CRC, these findings support periodic, ongoing surveillance colonoscopy in these patients,” wrote Benjamin Click, MD, of the division of gastroenterology, hepatology, and nutrition, University of Pittsburgh, and his coauthors.
Compared with patients who had no adenoma, those with advanced adenoma were significantly more likely to develop colorectal cancer (rate ratio, 2.7; 95% confidence interval, 1.9-3.7; P less than .001). By contrast, there was no significant difference in risk of colorectal cancer for patients with nonadvanced adenoma and no adenoma (RR, 1.2; 95% CI, 0.8-1.7; P = .30).
Risk of death related to colorectal cancer was also significantly increased for patients with advanced adenoma versus no adenoma, and again, the investigators said, no such difference in mortality was found when nonadvanced adenoma was compared with no adenoma.
The PLCO screening study enrolled men and women aged 55-74 years beginning in 1993, with follow-up continuing until Dec. 31, 2013.
Small, nonadvanced adenomas are commonly found in colonoscopy, occurring in approximately 30% of patients, the investigators said. In the United States, when patients have one to two nonadvanced adenomas, they are typically advised to return in 5-10 years, the researchers noted. However, evidence is lacking in terms of who should return in 5 years, as opposed to 10 years.
“If appropriately powered prospective trials were to replicate these findings, demonstrating no significant difference in cancer incidence between participants with 1 to 2 nonadvanced adenoma(s) and no adenomas, colonoscopy use could be reduced by a large extent, as a surveillance examination at 5 years would not be needed,” the study authors said.
The National Cancer Institute Division of Cancer Prevention supported the study. One author reported receiving grant support from Medtronic.
SOURCE: Click B et al. JAMA. 2018;319(19):2021-31.
Advanced adenomas found on diagnostic colonoscopy were associated with increased risk of developing colorectal cancer, while nonadvanced adenomas were not, according to long-term follow-up results from a large screening study.
The findings come from a post hoc analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial that enrolled 154,900 individuals, of whom 15,935 underwent colonoscopy following an abnormal flexible sigmoidoscopy screening result.
With a median of 13 years of follow-up, the incidence of colorectal cancer was 20.0 per 10,000 person-years for patients who had advanced adenoma found on colonoscopy, according to a report on the study published in JAMA. By comparison, colorectal cancer incidence was 9.1 and 7.5 per 10,000 person-years for nonadvanced adenoma and no adenoma, respectively.
“By demonstrating that individuals diagnosed with an advanced adenoma are at increased long-term risk for subsequent incident CRC, these findings support periodic, ongoing surveillance colonoscopy in these patients,” wrote Benjamin Click, MD, of the division of gastroenterology, hepatology, and nutrition, University of Pittsburgh, and his coauthors.
Compared with patients who had no adenoma, those with advanced adenoma were significantly more likely to develop colorectal cancer (rate ratio, 2.7; 95% confidence interval, 1.9-3.7; P less than .001). By contrast, there was no significant difference in risk of colorectal cancer for patients with nonadvanced adenoma and no adenoma (RR, 1.2; 95% CI, 0.8-1.7; P = .30).
Risk of death related to colorectal cancer was also significantly increased for patients with advanced adenoma versus no adenoma, and again, the investigators said, no such difference in mortality was found when nonadvanced adenoma was compared with no adenoma.
The PLCO screening study enrolled men and women aged 55-74 years beginning in 1993, with follow-up continuing until Dec. 31, 2013.
Small, nonadvanced adenomas are commonly found in colonoscopy, occurring in approximately 30% of patients, the investigators said. In the United States, when patients have one to two nonadvanced adenomas, they are typically advised to return in 5-10 years, the researchers noted. However, evidence is lacking in terms of who should return in 5 years, as opposed to 10 years.
“If appropriately powered prospective trials were to replicate these findings, demonstrating no significant difference in cancer incidence between participants with 1 to 2 nonadvanced adenoma(s) and no adenomas, colonoscopy use could be reduced by a large extent, as a surveillance examination at 5 years would not be needed,” the study authors said.
The National Cancer Institute Division of Cancer Prevention supported the study. One author reported receiving grant support from Medtronic.
SOURCE: Click B et al. JAMA. 2018;319(19):2021-31.
Advanced adenomas found on diagnostic colonoscopy were associated with increased risk of developing colorectal cancer, while nonadvanced adenomas were not, according to long-term follow-up results from a large screening study.
The findings come from a post hoc analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial that enrolled 154,900 individuals, of whom 15,935 underwent colonoscopy following an abnormal flexible sigmoidoscopy screening result.
With a median of 13 years of follow-up, the incidence of colorectal cancer was 20.0 per 10,000 person-years for patients who had advanced adenoma found on colonoscopy, according to a report on the study published in JAMA. By comparison, colorectal cancer incidence was 9.1 and 7.5 per 10,000 person-years for nonadvanced adenoma and no adenoma, respectively.
“By demonstrating that individuals diagnosed with an advanced adenoma are at increased long-term risk for subsequent incident CRC, these findings support periodic, ongoing surveillance colonoscopy in these patients,” wrote Benjamin Click, MD, of the division of gastroenterology, hepatology, and nutrition, University of Pittsburgh, and his coauthors.
Compared with patients who had no adenoma, those with advanced adenoma were significantly more likely to develop colorectal cancer (rate ratio, 2.7; 95% confidence interval, 1.9-3.7; P less than .001). By contrast, there was no significant difference in risk of colorectal cancer for patients with nonadvanced adenoma and no adenoma (RR, 1.2; 95% CI, 0.8-1.7; P = .30).
Risk of death related to colorectal cancer was also significantly increased for patients with advanced adenoma versus no adenoma, and again, the investigators said, no such difference in mortality was found when nonadvanced adenoma was compared with no adenoma.
The PLCO screening study enrolled men and women aged 55-74 years beginning in 1993, with follow-up continuing until Dec. 31, 2013.
Small, nonadvanced adenomas are commonly found in colonoscopy, occurring in approximately 30% of patients, the investigators said. In the United States, when patients have one to two nonadvanced adenomas, they are typically advised to return in 5-10 years, the researchers noted. However, evidence is lacking in terms of who should return in 5 years, as opposed to 10 years.
“If appropriately powered prospective trials were to replicate these findings, demonstrating no significant difference in cancer incidence between participants with 1 to 2 nonadvanced adenoma(s) and no adenomas, colonoscopy use could be reduced by a large extent, as a surveillance examination at 5 years would not be needed,” the study authors said.
The National Cancer Institute Division of Cancer Prevention supported the study. One author reported receiving grant support from Medtronic.
SOURCE: Click B et al. JAMA. 2018;319(19):2021-31.
FROM JAMA
Key clinical point: The risk of developing colorectal cancer was significantly increased for individuals with an advanced adenoma at diagnostic colonoscopy.
Major finding: With a median follow-up of 12.9 years, the incidence of colorectal cancer was 20.0 per 10,000 person-years for advanced adenoma, compared with 9.1 and 7.5 per 10,000 person-years for nonadvanced adenoma and no adenoma, respectively.
Study details: A multicenter, prospective cohort study of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer randomized clinical trial of flexible sigmoidoscopy that enrolled 154,900 individuals.
Disclosures: The National Cancer Institute Division of Cancer Prevention supported the study. One author reported receiving grant support from Medtronic.
Source: Click B et al. JAMA. 2018;319(19):2021-31.
MDedge Daily News: Gun ownership, suicide link largely ignored
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Listen to the MDedge Daily News podcast for all the details on today’s top news.
Words do matter – especially in psychiatry
As psychiatrists, we must be more precise with our language. When we speak, we must not use psychiatric diagnoses to describe common, everyday problems in life.
For example, at the recent American Psychiatric Association meeting in New York City, I frequently heard my colleagues talking about being “traumatized” over a microinsult or a microaggression. Although these individuals suggested that they were so fragile and vulnerable that stressful events caused them to develop posttraumatic stress disorder (PTSD), I seriously doubted it. Moreover, with further dialogue, it became clear that they were stressed or distressed over the stressful event – not traumatized in the purest sense of the term.
Traumatic stress, on the other hand, is an event that is so painful and disruptive that it runs the risk of breaking the mind’s ability to process or make peace with the event because it is so overwhelming that it disrupts or destroys normal psychic life. Such an event has the potential of causing PTSD, which is a chronic anxiety disorder that needs to be addressed clinically. This precision may seem nitpicky; however, the research on traumatic stress is clear. If you expose 100 people to a genuine traumatic experience, about 10% of the males and 20% of the females will develop PTSD, thus, something must be protecting people from developing PTSD from exposure to trauma. The research also is lucid that catastrophizing increases the risk of developing PTSD from exposure to a trauma by about 33%, and not having a sense of self-efficacy increases the risk by an additional 33%. Accordingly, , as this is catastrophizing and minimizes the belief in self-efficacy.
Similarly, we must be careful how we use the word “depression.” My understanding is depression is a clinical phenomenon that can be disabling. Unfortunately, I often hear patients and others talking about how they are depressed over various events in life that to me are a part of living, for example, being out of a job and not being able to make a way in life. Of course, if you are out actively looking for a job, that is probably not a clinical depression that would respond to antidepressant medication, but which would respond to finding a job. If a person were depressed from not having a job and unable to summon the energy to look for a job for 2 weeks or longer, I possibly would consider them clinically depressed. It seems laypeople are always using the word “depression” interchangeably for “unhappy,” “sad,” “grief,” or even “demoralization,” and although they all have common threads and are interlinked to one another, they are also very different.
Finally, the use of the word “bipolar” seems to be creeping into common usage, as I frequently hear patients who have poor affect regulation, for example, bad tempers, referring to themselves as being “bipolar.” However, after more dialogue, it becomes clear that they are describing a loss of self-control that lasts for maybe for 30 minutes or an hour. What is more distressing are the number of psychiatrists who are willing to take the patients’ word for it that they are “bipolar” and willing to prescribe mood stabilizers for such patients.
We must do better. We must not mislead the public into thinking that the ordinary problems of living are psychiatric disorders.
Dr. Bell is staff psychiatrist at Jackson Park Hospital Surgical-Medical/Psychiatric Inpatient Unit; clinical professor emeritus, department of psychiatry, University of Illinois at Chicago; and former director of the Institute for Juvenile Research (the birthplace of child psychiatry), all in Chicago. He also serves as chair of psychiatry at Windsor University, St. Kitts.
As psychiatrists, we must be more precise with our language. When we speak, we must not use psychiatric diagnoses to describe common, everyday problems in life.
For example, at the recent American Psychiatric Association meeting in New York City, I frequently heard my colleagues talking about being “traumatized” over a microinsult or a microaggression. Although these individuals suggested that they were so fragile and vulnerable that stressful events caused them to develop posttraumatic stress disorder (PTSD), I seriously doubted it. Moreover, with further dialogue, it became clear that they were stressed or distressed over the stressful event – not traumatized in the purest sense of the term.
Traumatic stress, on the other hand, is an event that is so painful and disruptive that it runs the risk of breaking the mind’s ability to process or make peace with the event because it is so overwhelming that it disrupts or destroys normal psychic life. Such an event has the potential of causing PTSD, which is a chronic anxiety disorder that needs to be addressed clinically. This precision may seem nitpicky; however, the research on traumatic stress is clear. If you expose 100 people to a genuine traumatic experience, about 10% of the males and 20% of the females will develop PTSD, thus, something must be protecting people from developing PTSD from exposure to trauma. The research also is lucid that catastrophizing increases the risk of developing PTSD from exposure to a trauma by about 33%, and not having a sense of self-efficacy increases the risk by an additional 33%. Accordingly, , as this is catastrophizing and minimizes the belief in self-efficacy.
Similarly, we must be careful how we use the word “depression.” My understanding is depression is a clinical phenomenon that can be disabling. Unfortunately, I often hear patients and others talking about how they are depressed over various events in life that to me are a part of living, for example, being out of a job and not being able to make a way in life. Of course, if you are out actively looking for a job, that is probably not a clinical depression that would respond to antidepressant medication, but which would respond to finding a job. If a person were depressed from not having a job and unable to summon the energy to look for a job for 2 weeks or longer, I possibly would consider them clinically depressed. It seems laypeople are always using the word “depression” interchangeably for “unhappy,” “sad,” “grief,” or even “demoralization,” and although they all have common threads and are interlinked to one another, they are also very different.
Finally, the use of the word “bipolar” seems to be creeping into common usage, as I frequently hear patients who have poor affect regulation, for example, bad tempers, referring to themselves as being “bipolar.” However, after more dialogue, it becomes clear that they are describing a loss of self-control that lasts for maybe for 30 minutes or an hour. What is more distressing are the number of psychiatrists who are willing to take the patients’ word for it that they are “bipolar” and willing to prescribe mood stabilizers for such patients.
We must do better. We must not mislead the public into thinking that the ordinary problems of living are psychiatric disorders.
Dr. Bell is staff psychiatrist at Jackson Park Hospital Surgical-Medical/Psychiatric Inpatient Unit; clinical professor emeritus, department of psychiatry, University of Illinois at Chicago; and former director of the Institute for Juvenile Research (the birthplace of child psychiatry), all in Chicago. He also serves as chair of psychiatry at Windsor University, St. Kitts.
As psychiatrists, we must be more precise with our language. When we speak, we must not use psychiatric diagnoses to describe common, everyday problems in life.
For example, at the recent American Psychiatric Association meeting in New York City, I frequently heard my colleagues talking about being “traumatized” over a microinsult or a microaggression. Although these individuals suggested that they were so fragile and vulnerable that stressful events caused them to develop posttraumatic stress disorder (PTSD), I seriously doubted it. Moreover, with further dialogue, it became clear that they were stressed or distressed over the stressful event – not traumatized in the purest sense of the term.
Traumatic stress, on the other hand, is an event that is so painful and disruptive that it runs the risk of breaking the mind’s ability to process or make peace with the event because it is so overwhelming that it disrupts or destroys normal psychic life. Such an event has the potential of causing PTSD, which is a chronic anxiety disorder that needs to be addressed clinically. This precision may seem nitpicky; however, the research on traumatic stress is clear. If you expose 100 people to a genuine traumatic experience, about 10% of the males and 20% of the females will develop PTSD, thus, something must be protecting people from developing PTSD from exposure to trauma. The research also is lucid that catastrophizing increases the risk of developing PTSD from exposure to a trauma by about 33%, and not having a sense of self-efficacy increases the risk by an additional 33%. Accordingly, , as this is catastrophizing and minimizes the belief in self-efficacy.
Similarly, we must be careful how we use the word “depression.” My understanding is depression is a clinical phenomenon that can be disabling. Unfortunately, I often hear patients and others talking about how they are depressed over various events in life that to me are a part of living, for example, being out of a job and not being able to make a way in life. Of course, if you are out actively looking for a job, that is probably not a clinical depression that would respond to antidepressant medication, but which would respond to finding a job. If a person were depressed from not having a job and unable to summon the energy to look for a job for 2 weeks or longer, I possibly would consider them clinically depressed. It seems laypeople are always using the word “depression” interchangeably for “unhappy,” “sad,” “grief,” or even “demoralization,” and although they all have common threads and are interlinked to one another, they are also very different.
Finally, the use of the word “bipolar” seems to be creeping into common usage, as I frequently hear patients who have poor affect regulation, for example, bad tempers, referring to themselves as being “bipolar.” However, after more dialogue, it becomes clear that they are describing a loss of self-control that lasts for maybe for 30 minutes or an hour. What is more distressing are the number of psychiatrists who are willing to take the patients’ word for it that they are “bipolar” and willing to prescribe mood stabilizers for such patients.
We must do better. We must not mislead the public into thinking that the ordinary problems of living are psychiatric disorders.
Dr. Bell is staff psychiatrist at Jackson Park Hospital Surgical-Medical/Psychiatric Inpatient Unit; clinical professor emeritus, department of psychiatry, University of Illinois at Chicago; and former director of the Institute for Juvenile Research (the birthplace of child psychiatry), all in Chicago. He also serves as chair of psychiatry at Windsor University, St. Kitts.
Tracking Down ‘Unusually’ Resistant Germs
According to the Centers for Disease Control and Prevention’s (CDC) study, 1 in 4 germ samples sent to the AR Lab Network for testing had special genes that allow them to spread their resistance to other germs. Further investigation in facilities with unusual resistance revealed that about 1 in 10 screening tests from patients without symptoms identified a hard-to-treat germ that spreads easily, meaning the germ could have spread undetected in that health care facility, the CDC said.
The CDC containment strategy includes continued infection control assessments until spread is stopped, which takes a coordinated response among facilities, labs, health departments, and CDC through the AR Lab Network. Health departments using the approach have conducted infection control assessments and colonization screenings within 48 hours of finding unusual resistance and have reported no further transmission during follow-up over several weeks. Estimates show that for carbapenem-resistant Enterobacteriaceae alone, the containment strategy would prevent as many as 1,600 new infections in 3 years in a single state—a 76% reduction.
Health care practitioners can help by using contact precautions, asking patients about recent travel or health care, and communicating about status when patients are transferred.
According to the Centers for Disease Control and Prevention’s (CDC) study, 1 in 4 germ samples sent to the AR Lab Network for testing had special genes that allow them to spread their resistance to other germs. Further investigation in facilities with unusual resistance revealed that about 1 in 10 screening tests from patients without symptoms identified a hard-to-treat germ that spreads easily, meaning the germ could have spread undetected in that health care facility, the CDC said.
The CDC containment strategy includes continued infection control assessments until spread is stopped, which takes a coordinated response among facilities, labs, health departments, and CDC through the AR Lab Network. Health departments using the approach have conducted infection control assessments and colonization screenings within 48 hours of finding unusual resistance and have reported no further transmission during follow-up over several weeks. Estimates show that for carbapenem-resistant Enterobacteriaceae alone, the containment strategy would prevent as many as 1,600 new infections in 3 years in a single state—a 76% reduction.
Health care practitioners can help by using contact precautions, asking patients about recent travel or health care, and communicating about status when patients are transferred.
According to the Centers for Disease Control and Prevention’s (CDC) study, 1 in 4 germ samples sent to the AR Lab Network for testing had special genes that allow them to spread their resistance to other germs. Further investigation in facilities with unusual resistance revealed that about 1 in 10 screening tests from patients without symptoms identified a hard-to-treat germ that spreads easily, meaning the germ could have spread undetected in that health care facility, the CDC said.
The CDC containment strategy includes continued infection control assessments until spread is stopped, which takes a coordinated response among facilities, labs, health departments, and CDC through the AR Lab Network. Health departments using the approach have conducted infection control assessments and colonization screenings within 48 hours of finding unusual resistance and have reported no further transmission during follow-up over several weeks. Estimates show that for carbapenem-resistant Enterobacteriaceae alone, the containment strategy would prevent as many as 1,600 new infections in 3 years in a single state—a 76% reduction.
Health care practitioners can help by using contact precautions, asking patients about recent travel or health care, and communicating about status when patients are transferred.
FDA approves new use for Zika test
The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.
The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.
The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.
The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.
Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.
Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.
This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.
The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.
“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.
The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.
The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.
The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.
The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.
Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.
Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.
This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.
The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.
“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.
The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.
The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.
The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.
The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.
Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.
Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.
This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.
The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.
“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.
Study reveals gender imbalance in cancer research funding
A new study suggests male investigators in the UK receive more funding for cancer research than their female counterparts.
Researchers analyzed funding for more than 4000 studies and found that male primary investigators (PIs) were consistently awarded more funding.
The total investment value was 3.6 times greater for male PIs than for female PIs.
The mean award value was 1.6 times greater, and the median award value was 1.3 times greater for males.
Rifat Atun, MBBS, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in BMJ Open.
The researchers analyzed data on public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013.
From this data, the team identified 4186 eligible studies with a total investment value of £2.33 billion.
The researchers compared the total investment, number of awards, and mean and median award value between male and female PIs.
Male PIs were awarded 2890 (69%) grants with a total value of £1.8 billion (78%), while female PIs were awarded 1296 (31%) grants with a total value of £0.5 billion (22%).
The median award value was £252,647 (interquartile range, £127,343–£553,560) for men and £198,485 (interquartile range, £99,317–£382,650) for women.
The mean award value was £630,324 (standard deviation, £1,662,559) for men and £394,730 (standard deviation, £666,574) for women.
Dr Atun and his colleagues acknowledged that this study was dependent on the accuracy of original investment data from the funding bodies, and the team could not openly access data of private sector research funding nor obtain disaggregated data from Cancer Research UK, one of the largest funders of cancer research.
The researchers also noted that the gender discrepancies they observed “are likely multifactorial,” and the team was unable to “postulate the underlying mechanisms responsible.” Still, the data do suggest a “substantial” imbalance, which should be investigated.
A new study suggests male investigators in the UK receive more funding for cancer research than their female counterparts.
Researchers analyzed funding for more than 4000 studies and found that male primary investigators (PIs) were consistently awarded more funding.
The total investment value was 3.6 times greater for male PIs than for female PIs.
The mean award value was 1.6 times greater, and the median award value was 1.3 times greater for males.
Rifat Atun, MBBS, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in BMJ Open.
The researchers analyzed data on public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013.
From this data, the team identified 4186 eligible studies with a total investment value of £2.33 billion.
The researchers compared the total investment, number of awards, and mean and median award value between male and female PIs.
Male PIs were awarded 2890 (69%) grants with a total value of £1.8 billion (78%), while female PIs were awarded 1296 (31%) grants with a total value of £0.5 billion (22%).
The median award value was £252,647 (interquartile range, £127,343–£553,560) for men and £198,485 (interquartile range, £99,317–£382,650) for women.
The mean award value was £630,324 (standard deviation, £1,662,559) for men and £394,730 (standard deviation, £666,574) for women.
Dr Atun and his colleagues acknowledged that this study was dependent on the accuracy of original investment data from the funding bodies, and the team could not openly access data of private sector research funding nor obtain disaggregated data from Cancer Research UK, one of the largest funders of cancer research.
The researchers also noted that the gender discrepancies they observed “are likely multifactorial,” and the team was unable to “postulate the underlying mechanisms responsible.” Still, the data do suggest a “substantial” imbalance, which should be investigated.
A new study suggests male investigators in the UK receive more funding for cancer research than their female counterparts.
Researchers analyzed funding for more than 4000 studies and found that male primary investigators (PIs) were consistently awarded more funding.
The total investment value was 3.6 times greater for male PIs than for female PIs.
The mean award value was 1.6 times greater, and the median award value was 1.3 times greater for males.
Rifat Atun, MBBS, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and his colleagues reported these findings in BMJ Open.
The researchers analyzed data on public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013.
From this data, the team identified 4186 eligible studies with a total investment value of £2.33 billion.
The researchers compared the total investment, number of awards, and mean and median award value between male and female PIs.
Male PIs were awarded 2890 (69%) grants with a total value of £1.8 billion (78%), while female PIs were awarded 1296 (31%) grants with a total value of £0.5 billion (22%).
The median award value was £252,647 (interquartile range, £127,343–£553,560) for men and £198,485 (interquartile range, £99,317–£382,650) for women.
The mean award value was £630,324 (standard deviation, £1,662,559) for men and £394,730 (standard deviation, £666,574) for women.
Dr Atun and his colleagues acknowledged that this study was dependent on the accuracy of original investment data from the funding bodies, and the team could not openly access data of private sector research funding nor obtain disaggregated data from Cancer Research UK, one of the largest funders of cancer research.
The researchers also noted that the gender discrepancies they observed “are likely multifactorial,” and the team was unable to “postulate the underlying mechanisms responsible.” Still, the data do suggest a “substantial” imbalance, which should be investigated.
NCCN releases guidelines for AML patients
The National Comprehensive Cancer Network (NCCN) has released guidelines for patients with acute myeloid leukemia (AML).
The guidelines are intended to help patients make better informed decision about their care.
The guidelines explain what AML is, describe testing procedures and treatment options, and provide tips to help patients choose the best treatment.
The guidelines also include a list of suggested questions for patients to bring up with their doctors, illustrations, and a glossary of key terms and acronyms.
“People with AML often aren’t aware that this isn’t a single disease but many different diseases that share fundamental characteristics,” said Martin Tallman, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, and vice-chair of the NCCN Guidelines Panel for AML.
“The good news is that the future for AML is getting a lot brighter. After 40 years without much progress, 4 new medications were just approved last year*, and more new treatment courses are in development as we speak.”
The guidelines are available for free on the NCCN website or via the NCCN Patient Guides for Cancer app. Printed versions of the guidelines can be purchased at Amazon.com.
NCCN also has guidelines for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin lymphoma, multiple myeloma, myelodysplastic syndromes, myeloproliferative neoplasms, non-Hodgkin lymphomas, and Waldenström’s macroglobulinemia, as well as solid tumor malignancies.
There are patient guidelines for adolescents and young adults with cancer and guidelines on distress/supportive care, and nausea and vomiting/supportive care as well.
*(1) Midostaurin (Rydapt) was approved for adults with newly diagnosed, FLT3-positive AML
(2) Gemtuzumab ozogamicin (Mylotarg) was approved for adults with newly diagnosed AML and patients age 2 and older with relapsed/refractory AML
(3) Liposomal daunorubicin/cytarabine (Vyxeos) was approved for AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML
(4) Enasidenib (Idhifa) was approved for adults with relapsed/refractory AML and an IDH2 mutation.
The National Comprehensive Cancer Network (NCCN) has released guidelines for patients with acute myeloid leukemia (AML).
The guidelines are intended to help patients make better informed decision about their care.
The guidelines explain what AML is, describe testing procedures and treatment options, and provide tips to help patients choose the best treatment.
The guidelines also include a list of suggested questions for patients to bring up with their doctors, illustrations, and a glossary of key terms and acronyms.
“People with AML often aren’t aware that this isn’t a single disease but many different diseases that share fundamental characteristics,” said Martin Tallman, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, and vice-chair of the NCCN Guidelines Panel for AML.
“The good news is that the future for AML is getting a lot brighter. After 40 years without much progress, 4 new medications were just approved last year*, and more new treatment courses are in development as we speak.”
The guidelines are available for free on the NCCN website or via the NCCN Patient Guides for Cancer app. Printed versions of the guidelines can be purchased at Amazon.com.
NCCN also has guidelines for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin lymphoma, multiple myeloma, myelodysplastic syndromes, myeloproliferative neoplasms, non-Hodgkin lymphomas, and Waldenström’s macroglobulinemia, as well as solid tumor malignancies.
There are patient guidelines for adolescents and young adults with cancer and guidelines on distress/supportive care, and nausea and vomiting/supportive care as well.
*(1) Midostaurin (Rydapt) was approved for adults with newly diagnosed, FLT3-positive AML
(2) Gemtuzumab ozogamicin (Mylotarg) was approved for adults with newly diagnosed AML and patients age 2 and older with relapsed/refractory AML
(3) Liposomal daunorubicin/cytarabine (Vyxeos) was approved for AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML
(4) Enasidenib (Idhifa) was approved for adults with relapsed/refractory AML and an IDH2 mutation.
The National Comprehensive Cancer Network (NCCN) has released guidelines for patients with acute myeloid leukemia (AML).
The guidelines are intended to help patients make better informed decision about their care.
The guidelines explain what AML is, describe testing procedures and treatment options, and provide tips to help patients choose the best treatment.
The guidelines also include a list of suggested questions for patients to bring up with their doctors, illustrations, and a glossary of key terms and acronyms.
“People with AML often aren’t aware that this isn’t a single disease but many different diseases that share fundamental characteristics,” said Martin Tallman, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, and vice-chair of the NCCN Guidelines Panel for AML.
“The good news is that the future for AML is getting a lot brighter. After 40 years without much progress, 4 new medications were just approved last year*, and more new treatment courses are in development as we speak.”
The guidelines are available for free on the NCCN website or via the NCCN Patient Guides for Cancer app. Printed versions of the guidelines can be purchased at Amazon.com.
NCCN also has guidelines for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin lymphoma, multiple myeloma, myelodysplastic syndromes, myeloproliferative neoplasms, non-Hodgkin lymphomas, and Waldenström’s macroglobulinemia, as well as solid tumor malignancies.
There are patient guidelines for adolescents and young adults with cancer and guidelines on distress/supportive care, and nausea and vomiting/supportive care as well.
*(1) Midostaurin (Rydapt) was approved for adults with newly diagnosed, FLT3-positive AML
(2) Gemtuzumab ozogamicin (Mylotarg) was approved for adults with newly diagnosed AML and patients age 2 and older with relapsed/refractory AML
(3) Liposomal daunorubicin/cytarabine (Vyxeos) was approved for AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML
(4) Enasidenib (Idhifa) was approved for adults with relapsed/refractory AML and an IDH2 mutation.
Treating Migraines: It’s Different for Kids
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
Sarcoma dominance in uterine carcinosarcomas linked to decreased survival
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
Sarcoma dominance in uterine carcinosarcomas was associated with decreased survival among women with stages I-IV uterine carcinosarcomas who underwent primary surgery, according to Dr Koji Matsuo, MD, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, and his colleagues.
The researchers additionally found that adding radiotherapy to chemotherapy may be an effective postoperative strategy for these patients.
Uterine carcinosarcomas are rare, high-grade endometrial cancers that represent 5% of all endometrial cancers. Sarcoma dominance was defined as having more than a 50% sarcoma component in the uterine tumor. In this study, the sarcoma component was grouped as homologous (endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma, and undifferentiated sarcoma) or heterologous (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and liposarcoma) types
Among 1,192 cases of uterine carcinosarcomas identified in a secondary analysis of a multicenter retrospective study, 906 cases were available for histopathology slide review. Of those, 889 cases had evaluation for sarcoma dominance. The most common group was homologous sarcoma without sarcoma dominance (39.5%), followed by heterologous sarcoma with sarcoma dominance (21.3%), homologous sarcoma with sarcoma dominance (19.7%) and heterologous sarcoma with sarcoma non-dominance (19.6%), they reported in a study published online in Surgical Oncology https://doi.org/10.1016/j.suronc.2018.05.017
On univariate analysis, sarcoma dominance was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (P less than 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homologous/dominance 1.35-1.69, and heterologous/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homologous/non-dominance (all, P less than 0.05).
In women with stage I-III disease, and tumors with sarcoma dominance, adding radiotherapy to chemotherapy was associated with improved PFS (adjusted-HR: homologous/dominance 0.49, and heterologous/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P less than 0.05); This association was not observed in women with tumors that lacked sarcoma dominance (all, P greater than 0.05), the researchers said.
FROM SURGICAL ONCOLOGY
FDA seeks comments on pediatric HIV product development
The U.S. Food and Drug Administration announced a draft guidance for industry entitled “Pediatric HIV Infection: Drug Development for Treatment.” (from birth to younger than 17 years of age).
According to the FDA announcement, the draft includes recommendations on when sponsors should initiate pediatric formulation development and when to begin pediatric studies to evaluate antiretroviral drug products for the treatment of HIV infection.
SOURCE: Federal Register May 14. Pediatric HIV Infection: Drug Development for Treatment; Draft Guidance for Industry; Availability.
The U.S. Food and Drug Administration announced a draft guidance for industry entitled “Pediatric HIV Infection: Drug Development for Treatment.” (from birth to younger than 17 years of age).
According to the FDA announcement, the draft includes recommendations on when sponsors should initiate pediatric formulation development and when to begin pediatric studies to evaluate antiretroviral drug products for the treatment of HIV infection.
SOURCE: Federal Register May 14. Pediatric HIV Infection: Drug Development for Treatment; Draft Guidance for Industry; Availability.
The U.S. Food and Drug Administration announced a draft guidance for industry entitled “Pediatric HIV Infection: Drug Development for Treatment.” (from birth to younger than 17 years of age).
According to the FDA announcement, the draft includes recommendations on when sponsors should initiate pediatric formulation development and when to begin pediatric studies to evaluate antiretroviral drug products for the treatment of HIV infection.
SOURCE: Federal Register May 14. Pediatric HIV Infection: Drug Development for Treatment; Draft Guidance for Industry; Availability.