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Twin study offers new insight into genetics of migraine
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
DENVER – , even though testosterone is thought to be protective. The findings, presented at the annual meeting of the American Headache Society, also hint at a possible role played by the prenatal environment.
The study marks the first time a large-scale twin dataset has been used to assess sex differences in underlying genetic factors of migraine, lead author Morgan Fitzgerald, a senior research associate at the University of California at San Diego, said in a presentation at the conference. The findings were previously published in Frontiers in Pain Research.
More than genetics
The researchers analyzed data regarding 51,872 participants in the Swedish Twin Registry. According to Dr. Fitzgerald, the database is ideal because it is large and includes both genders.
Per the database, female twins were more likely to have migraines without aura than were male twins (17.6% vs. 5.5%, respectively), reflecting global numbers that suggest 18% of females and 6% of males have migraines each year.
To better understand heritability, the researchers compared identical twins with fraternal twins, and looked for gender-related correlations, Dr. Fitzgerald said.
One analysis suggests that migraine is equally heritable in men and women with a broad sense heritability of 0.45 (95% confidence interval [CI], 0.40-0.50). However, another analysis model provides evidence “that there are differences in the underlying genetic factors contributing to migraine across males and females,” she said.
Unexpectedly, the researchers also found that females with male twins were more likely to have migraines than were those with female twins (odds ratio, 1.51, 95% CI, 1.26-1.81) even though males are less affected by the headaches.
“These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females,” the authors wrote in the published study. “This effect points to a potential prenatal neuroendocrine factor in the development of migraine.”
Probing the migraine gender gap
Commenting on the research, University of Texas at Dallas neuroscientist and headache researcher Gregory Dussor, PhD, said the new study is “a very unique approach to address the question of nature versus nurture in migraine. It was well designed and used robust statistical modeling.”
As for the findings, “the conclusion that genetics do not explain sex differences in migraine risk by themselves is not surprising given how big of a role hormones in later life are likely to play in the disease and how many factors there are that can influence hormone levels,” he said.
“On the other hand, the surprising part of the findings was that the presence of a male co-twin increases risk of migraine in females. I would have expected to see the opposite, given the lower prevalence of migraine in males and the seemingly protective role that male hormones can play in migraine.”
Overall, the study adds to data implicating environment and hormones in the migraine gender gap, he said. “One thing I wonder from this study is what influence a female co-twin growing up with a male co-twin can have on migraine susceptibility. That female co-twin may end up with a very different set of childhood experiences than if she was with another female co-twin. Twins generally spend an enormous amount of time together and the same sex versus opposite sex experiences are likely to be quite different. This may have an influence on migraine later in life.”
As for the value of the study in terms of diagnosis, treatment, or prevention of migraine, Dr. Dussor said, “it’s possible it could help to identify risk factors for higher migraine susceptibility but it’s far too early to know how this could be used.”
The authors have no disclosures. Dr. Dussor disclosed an NIH-funded grant to study the role of the hormone prolactin in preclinical migraine models.
AT AHS 2022
Melanoma incidence is up, but death rates are down
CHICAGO – , according to a new analysis of the National Cancer Institute SEER database between 1975 and 2019.
“This is very encouraging data and represents the real-world effectiveness of these therapies. The cost of these therapies can be prohibitive for universal treatment access, so the ways to address the accessibility of these treatments and the health care costs need to be supported,” said lead author Navkirat Kaur Kahlon MD, a hematology/oncology fellow at the University of Toledo (Ohio). The study was presented at the annual meeting of the American Society of Clinical Oncology.
According to the American Cancer Society, the 5-year mortality for regional melanoma metastasis is 68%, and 30% for distant metastasis. However, these numbers may underestimate current survival. “People now being diagnosed with melanoma may have a better outlook than these numbers show. Treatments have improved over time, and these numbers are based on people who were diagnosed and treated at least 5 years earlier,” the American Cancer Society wrote.
Other studies have found similar trends. According to Cancer Research UK, 5-year melanoma skin cancer survival approximately doubled, from 46% to 90%, between 1971 and 2010. And, 1-year survival increased from 74% to 96%, but these improvements predated immune checkpoint inhibitors. An analysis of the Canadian Cancer Registry and Canadian Vital Statistics found an increasing incidence of melanoma, but a drop in mortality since 2013. A study of melanoma outcomes in Hungary also found increased incidence, while mortality declined by 16.55% between 2011 and 2019 (P =.013).
“These new drugs, which include immunotherapies and targeted therapies, are effective treatments in the clinical trial data, so the magnitude of drop seen in population mortality was not surprising but very exciting,” Dr. Kahlon said.
The findings are encouraging, but prevention remains the most important strategy. “The utility of sun-protective strategies and policies should be encouraged,” she added.
Cytotoxic chemotherapy has poor efficacy against metastatic melanoma, but novel therapies such as checkpoint inhibitors increased expected survival from months to years. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world population is deriving the same benefit,” Dr. Kahlon said.
The researchers found that the annual percentage change (APC) melanoma mortality rate (MMR) was +1.65% between 1975 and 1988 (P < .01). The APC was 0.01% between 1988 and 2013, which was not statistically significant (P = .85). Between 2013 and 2017, APC was –6.24% (P < .01), and it was –1.56% between 2017 and 2019 (P = .53).
The increase in melanoma mortality between 1975 and 1988 may be due to changes in the way that SEER data was collected. “It is possible that this increase was at least in part due to better capturing of the data. There may also be a contribution of increased mortality due to increased incidence of diagnoses related to increased UV exposure. From the 1920s, increased sun exposure and bronzed skin became fashionable. In the 1940s-1960s, tanning oils and lotions became more popular, and there may have been an increase in UV exposure during that time, which later led to an increase in diagnosis and, without effective therapies, mortality. Further, the use of indoor tanning beds from the 1970s onward may have contributed to increased UV exposure, incidence, and mortality,” she said.
On the other hand, the researchers noted a slowing of mortality reduction between 2017 and 2019. This was not a surprise, Dr. Kahlon said, since by that time most novel therapies were being introduced in the adjuvant setting. “The mortality benefit, if any, from adjuvant treatments is seen over a longer period and may not yet be captured in SEER data. Even the clinical trial data for most of these treatments have not shown an overall survival advantage and require more time for the data to mature. It will be interesting to see how these trends change in the near future,” Dr. Kahlon said.
The study was limited by its retrospective nature. Dr. Kahlon has no relevant financial disclosures.
CHICAGO – , according to a new analysis of the National Cancer Institute SEER database between 1975 and 2019.
“This is very encouraging data and represents the real-world effectiveness of these therapies. The cost of these therapies can be prohibitive for universal treatment access, so the ways to address the accessibility of these treatments and the health care costs need to be supported,” said lead author Navkirat Kaur Kahlon MD, a hematology/oncology fellow at the University of Toledo (Ohio). The study was presented at the annual meeting of the American Society of Clinical Oncology.
According to the American Cancer Society, the 5-year mortality for regional melanoma metastasis is 68%, and 30% for distant metastasis. However, these numbers may underestimate current survival. “People now being diagnosed with melanoma may have a better outlook than these numbers show. Treatments have improved over time, and these numbers are based on people who were diagnosed and treated at least 5 years earlier,” the American Cancer Society wrote.
Other studies have found similar trends. According to Cancer Research UK, 5-year melanoma skin cancer survival approximately doubled, from 46% to 90%, between 1971 and 2010. And, 1-year survival increased from 74% to 96%, but these improvements predated immune checkpoint inhibitors. An analysis of the Canadian Cancer Registry and Canadian Vital Statistics found an increasing incidence of melanoma, but a drop in mortality since 2013. A study of melanoma outcomes in Hungary also found increased incidence, while mortality declined by 16.55% between 2011 and 2019 (P =.013).
“These new drugs, which include immunotherapies and targeted therapies, are effective treatments in the clinical trial data, so the magnitude of drop seen in population mortality was not surprising but very exciting,” Dr. Kahlon said.
The findings are encouraging, but prevention remains the most important strategy. “The utility of sun-protective strategies and policies should be encouraged,” she added.
Cytotoxic chemotherapy has poor efficacy against metastatic melanoma, but novel therapies such as checkpoint inhibitors increased expected survival from months to years. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world population is deriving the same benefit,” Dr. Kahlon said.
The researchers found that the annual percentage change (APC) melanoma mortality rate (MMR) was +1.65% between 1975 and 1988 (P < .01). The APC was 0.01% between 1988 and 2013, which was not statistically significant (P = .85). Between 2013 and 2017, APC was –6.24% (P < .01), and it was –1.56% between 2017 and 2019 (P = .53).
The increase in melanoma mortality between 1975 and 1988 may be due to changes in the way that SEER data was collected. “It is possible that this increase was at least in part due to better capturing of the data. There may also be a contribution of increased mortality due to increased incidence of diagnoses related to increased UV exposure. From the 1920s, increased sun exposure and bronzed skin became fashionable. In the 1940s-1960s, tanning oils and lotions became more popular, and there may have been an increase in UV exposure during that time, which later led to an increase in diagnosis and, without effective therapies, mortality. Further, the use of indoor tanning beds from the 1970s onward may have contributed to increased UV exposure, incidence, and mortality,” she said.
On the other hand, the researchers noted a slowing of mortality reduction between 2017 and 2019. This was not a surprise, Dr. Kahlon said, since by that time most novel therapies were being introduced in the adjuvant setting. “The mortality benefit, if any, from adjuvant treatments is seen over a longer period and may not yet be captured in SEER data. Even the clinical trial data for most of these treatments have not shown an overall survival advantage and require more time for the data to mature. It will be interesting to see how these trends change in the near future,” Dr. Kahlon said.
The study was limited by its retrospective nature. Dr. Kahlon has no relevant financial disclosures.
CHICAGO – , according to a new analysis of the National Cancer Institute SEER database between 1975 and 2019.
“This is very encouraging data and represents the real-world effectiveness of these therapies. The cost of these therapies can be prohibitive for universal treatment access, so the ways to address the accessibility of these treatments and the health care costs need to be supported,” said lead author Navkirat Kaur Kahlon MD, a hematology/oncology fellow at the University of Toledo (Ohio). The study was presented at the annual meeting of the American Society of Clinical Oncology.
According to the American Cancer Society, the 5-year mortality for regional melanoma metastasis is 68%, and 30% for distant metastasis. However, these numbers may underestimate current survival. “People now being diagnosed with melanoma may have a better outlook than these numbers show. Treatments have improved over time, and these numbers are based on people who were diagnosed and treated at least 5 years earlier,” the American Cancer Society wrote.
Other studies have found similar trends. According to Cancer Research UK, 5-year melanoma skin cancer survival approximately doubled, from 46% to 90%, between 1971 and 2010. And, 1-year survival increased from 74% to 96%, but these improvements predated immune checkpoint inhibitors. An analysis of the Canadian Cancer Registry and Canadian Vital Statistics found an increasing incidence of melanoma, but a drop in mortality since 2013. A study of melanoma outcomes in Hungary also found increased incidence, while mortality declined by 16.55% between 2011 and 2019 (P =.013).
“These new drugs, which include immunotherapies and targeted therapies, are effective treatments in the clinical trial data, so the magnitude of drop seen in population mortality was not surprising but very exciting,” Dr. Kahlon said.
The findings are encouraging, but prevention remains the most important strategy. “The utility of sun-protective strategies and policies should be encouraged,” she added.
Cytotoxic chemotherapy has poor efficacy against metastatic melanoma, but novel therapies such as checkpoint inhibitors increased expected survival from months to years. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world population is deriving the same benefit,” Dr. Kahlon said.
The researchers found that the annual percentage change (APC) melanoma mortality rate (MMR) was +1.65% between 1975 and 1988 (P < .01). The APC was 0.01% between 1988 and 2013, which was not statistically significant (P = .85). Between 2013 and 2017, APC was –6.24% (P < .01), and it was –1.56% between 2017 and 2019 (P = .53).
The increase in melanoma mortality between 1975 and 1988 may be due to changes in the way that SEER data was collected. “It is possible that this increase was at least in part due to better capturing of the data. There may also be a contribution of increased mortality due to increased incidence of diagnoses related to increased UV exposure. From the 1920s, increased sun exposure and bronzed skin became fashionable. In the 1940s-1960s, tanning oils and lotions became more popular, and there may have been an increase in UV exposure during that time, which later led to an increase in diagnosis and, without effective therapies, mortality. Further, the use of indoor tanning beds from the 1970s onward may have contributed to increased UV exposure, incidence, and mortality,” she said.
On the other hand, the researchers noted a slowing of mortality reduction between 2017 and 2019. This was not a surprise, Dr. Kahlon said, since by that time most novel therapies were being introduced in the adjuvant setting. “The mortality benefit, if any, from adjuvant treatments is seen over a longer period and may not yet be captured in SEER data. Even the clinical trial data for most of these treatments have not shown an overall survival advantage and require more time for the data to mature. It will be interesting to see how these trends change in the near future,” Dr. Kahlon said.
The study was limited by its retrospective nature. Dr. Kahlon has no relevant financial disclosures.
AT ASCO 2022
Highlights in Early-Stage Non–Small Cell Lung Cancer From ASCO 2022
Highlights in early-stage non–small lung cancer (NSCLC) from the 2022 American Society of Clinical Oncology Annual Meeting are discussed by Dr Jack West of City of Hope Comprehensive Cancer Center in Duarte, California.
He opens with a post hoc analysis of CheckMate 816, which showed that achieving a pathologic complete response with adjuvant nivolumab plus chemotherapy was highly associated with improved event-free survival.
Next, Dr West reports on early results from the NADIM II trial, which confirmed the superiority of neoadjuvant nivolumab plus chemotherapy in resectable stage IIIa NSCLC, as well as the need for careful patient selection.
He moves on to describe the neoSCORE study, which compared two vs three cycles of neoadjuvant sintilimab plus chemotherapy, with the latter achieving a markedly higher major pathologic response rate.
Dr West next examines two interventional studies, starting with an analysis of the SEER database, which showed that addition of radiation therapy to neoadjuvant chemotherapy does not offer a benefit. He ends with a Veterans Affairs study underlining the importance of surgical quality as a predictor of patient outcomes.
--
Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, California; Medical Director, AccessHope, Los Angeles, California
Howard (Jack) West, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Amgen; AstraZeneca; Eli Lily; EQRx; Genentech/Roche; Merck; Mirati; Pfizer; Regeneron; Takeda
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Merck
Highlights in early-stage non–small lung cancer (NSCLC) from the 2022 American Society of Clinical Oncology Annual Meeting are discussed by Dr Jack West of City of Hope Comprehensive Cancer Center in Duarte, California.
He opens with a post hoc analysis of CheckMate 816, which showed that achieving a pathologic complete response with adjuvant nivolumab plus chemotherapy was highly associated with improved event-free survival.
Next, Dr West reports on early results from the NADIM II trial, which confirmed the superiority of neoadjuvant nivolumab plus chemotherapy in resectable stage IIIa NSCLC, as well as the need for careful patient selection.
He moves on to describe the neoSCORE study, which compared two vs three cycles of neoadjuvant sintilimab plus chemotherapy, with the latter achieving a markedly higher major pathologic response rate.
Dr West next examines two interventional studies, starting with an analysis of the SEER database, which showed that addition of radiation therapy to neoadjuvant chemotherapy does not offer a benefit. He ends with a Veterans Affairs study underlining the importance of surgical quality as a predictor of patient outcomes.
--
Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, California; Medical Director, AccessHope, Los Angeles, California
Howard (Jack) West, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Amgen; AstraZeneca; Eli Lily; EQRx; Genentech/Roche; Merck; Mirati; Pfizer; Regeneron; Takeda
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Merck
Highlights in early-stage non–small lung cancer (NSCLC) from the 2022 American Society of Clinical Oncology Annual Meeting are discussed by Dr Jack West of City of Hope Comprehensive Cancer Center in Duarte, California.
He opens with a post hoc analysis of CheckMate 816, which showed that achieving a pathologic complete response with adjuvant nivolumab plus chemotherapy was highly associated with improved event-free survival.
Next, Dr West reports on early results from the NADIM II trial, which confirmed the superiority of neoadjuvant nivolumab plus chemotherapy in resectable stage IIIa NSCLC, as well as the need for careful patient selection.
He moves on to describe the neoSCORE study, which compared two vs three cycles of neoadjuvant sintilimab plus chemotherapy, with the latter achieving a markedly higher major pathologic response rate.
Dr West next examines two interventional studies, starting with an analysis of the SEER database, which showed that addition of radiation therapy to neoadjuvant chemotherapy does not offer a benefit. He ends with a Veterans Affairs study underlining the importance of surgical quality as a predictor of patient outcomes.
--
Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, California; Medical Director, AccessHope, Los Angeles, California
Howard (Jack) West, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Amgen; AstraZeneca; Eli Lily; EQRx; Genentech/Roche; Merck; Mirati; Pfizer; Regeneron; Takeda
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Merck
Jury out on low-FODMAP diet for kids
There is scarce evidence to support the use of a FODMAP-lowering diet for children with irritable bowel syndrome (IBS), and there is no evidence to recommend its use for other gastrointestinal (GI) diseases and complaints in children, according to a position paper from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
A low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is increasingly being used to treat children with various GI complaints and disorders.
“Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects,” the authors note.
Rut Anne Thomassen, department of pediatric medicine, Oslo University Hospital, and an international team of experts conducted a systematic literature review of the evidence on the safety and efficacy of the low-FODMAP diet in children.
The low-FODMAP diet has not been well studied in children, they report.
From 53 publications and registers that they screened, only seven studies (four randomized clinical trials and three interventions without control group or observational studies) were included in their assessment.
In the seven studies, only 111 children received the low-FODMAP diet, while 85 followed a control diet for comparison (a diet described as healthy, usual, or typical American diet for children).
All of the pediatric studies focused on functional abdominal pain disorders. None addressed nonceliac gluten sensitivity, small-intestinal bacterial overgrowth, or inflammatory bowel disease.
From their review, the authors conclude that, at present, there is “insufficient evidence” to routinely recommend the low-FODMAP diet for the treatment of functional GI disorders, nonceliac gluten sensitivity, inflammatory bowel diseases, or small-intestinal bacterial overgrowth in children.
When the low-FODMAP diet is considered for children, the authors recommend a thorough clinical history, physical examination, and assessment of nutritional status and GI symptoms by a multidisciplinary team.
“Ideally, a standardized questionnaire should be used before and following the start of the diet to assess objectively the effect of the low-FODMAP diet,” the authors advise.
A dietitian should assess the child’s diet to highlight any potential deficiencies, which could be exacerbated by the restrictions of the low-FODMAP diet.
To promote adherence to the diet, potential difficulties, such as how to provide a suitable lunch at school or what to do when the child is staying at a friend’s house, should be addressed.
The authors suggest providing parents with written information about sources of FODMAPs and suitable replacement foods. Offering meal plans can reduce the risk of diet mistakes as well as the risk of offering a diet insufficient in essential nutrients, they say.
‘Useful paper’
“This is a useful paper primarily to outline the paucity of data regarding dietary therapies in children and the importance of doing studies in this population,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, who wasn’t involved in the research, told this news organization.
Samuel Nurko, MD, MPH, director of the Center for Motility and Functional Gastrointestinal Disorders at Boston Children’s Hospital, Massachusetts, noted that some studies have shown that a low-FODMAP diet can be effective in controlling symptoms for both adults and kids.
“The problem in kids is that the trials are very small, and there’s not a lot of them, so the evidence is limited,” said Dr. Nurko, who wasn’t involved in writing the position paper.
That’s not to say that it should not be tried in appropriate cases. “There’s no question that in some patients, taking away the FODMAPs gives them a big improvement in GI symptoms,” Dr. Nurko told this news organization.
“The problem with the low-FODMAP diet is, if you don’t do it right, then you get into trouble with nutritional deficiencies,” he cautioned.
“If you are going to try the low-FODMAP diet, it has to be short, no more than 4-6 weeks, and you need to do a top-down approach. Take FODMAPs out, and then start to reintroduce them. Either kids will respond to the diet, or they won’t. If they don’t, there is no reason to keep them on the diet. It’s a very hard diet to take,” Dr. Nurko said.
No source of funding for the study was disclosed. The authors, Dr. Ananthakrishnan, and Dr. Nurko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
There is scarce evidence to support the use of a FODMAP-lowering diet for children with irritable bowel syndrome (IBS), and there is no evidence to recommend its use for other gastrointestinal (GI) diseases and complaints in children, according to a position paper from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
A low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is increasingly being used to treat children with various GI complaints and disorders.
“Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects,” the authors note.
Rut Anne Thomassen, department of pediatric medicine, Oslo University Hospital, and an international team of experts conducted a systematic literature review of the evidence on the safety and efficacy of the low-FODMAP diet in children.
The low-FODMAP diet has not been well studied in children, they report.
From 53 publications and registers that they screened, only seven studies (four randomized clinical trials and three interventions without control group or observational studies) were included in their assessment.
In the seven studies, only 111 children received the low-FODMAP diet, while 85 followed a control diet for comparison (a diet described as healthy, usual, or typical American diet for children).
All of the pediatric studies focused on functional abdominal pain disorders. None addressed nonceliac gluten sensitivity, small-intestinal bacterial overgrowth, or inflammatory bowel disease.
From their review, the authors conclude that, at present, there is “insufficient evidence” to routinely recommend the low-FODMAP diet for the treatment of functional GI disorders, nonceliac gluten sensitivity, inflammatory bowel diseases, or small-intestinal bacterial overgrowth in children.
When the low-FODMAP diet is considered for children, the authors recommend a thorough clinical history, physical examination, and assessment of nutritional status and GI symptoms by a multidisciplinary team.
“Ideally, a standardized questionnaire should be used before and following the start of the diet to assess objectively the effect of the low-FODMAP diet,” the authors advise.
A dietitian should assess the child’s diet to highlight any potential deficiencies, which could be exacerbated by the restrictions of the low-FODMAP diet.
To promote adherence to the diet, potential difficulties, such as how to provide a suitable lunch at school or what to do when the child is staying at a friend’s house, should be addressed.
The authors suggest providing parents with written information about sources of FODMAPs and suitable replacement foods. Offering meal plans can reduce the risk of diet mistakes as well as the risk of offering a diet insufficient in essential nutrients, they say.
‘Useful paper’
“This is a useful paper primarily to outline the paucity of data regarding dietary therapies in children and the importance of doing studies in this population,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, who wasn’t involved in the research, told this news organization.
Samuel Nurko, MD, MPH, director of the Center for Motility and Functional Gastrointestinal Disorders at Boston Children’s Hospital, Massachusetts, noted that some studies have shown that a low-FODMAP diet can be effective in controlling symptoms for both adults and kids.
“The problem in kids is that the trials are very small, and there’s not a lot of them, so the evidence is limited,” said Dr. Nurko, who wasn’t involved in writing the position paper.
That’s not to say that it should not be tried in appropriate cases. “There’s no question that in some patients, taking away the FODMAPs gives them a big improvement in GI symptoms,” Dr. Nurko told this news organization.
“The problem with the low-FODMAP diet is, if you don’t do it right, then you get into trouble with nutritional deficiencies,” he cautioned.
“If you are going to try the low-FODMAP diet, it has to be short, no more than 4-6 weeks, and you need to do a top-down approach. Take FODMAPs out, and then start to reintroduce them. Either kids will respond to the diet, or they won’t. If they don’t, there is no reason to keep them on the diet. It’s a very hard diet to take,” Dr. Nurko said.
No source of funding for the study was disclosed. The authors, Dr. Ananthakrishnan, and Dr. Nurko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
There is scarce evidence to support the use of a FODMAP-lowering diet for children with irritable bowel syndrome (IBS), and there is no evidence to recommend its use for other gastrointestinal (GI) diseases and complaints in children, according to a position paper from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).
A low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is increasingly being used to treat children with various GI complaints and disorders.
“Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects,” the authors note.
Rut Anne Thomassen, department of pediatric medicine, Oslo University Hospital, and an international team of experts conducted a systematic literature review of the evidence on the safety and efficacy of the low-FODMAP diet in children.
The low-FODMAP diet has not been well studied in children, they report.
From 53 publications and registers that they screened, only seven studies (four randomized clinical trials and three interventions without control group or observational studies) were included in their assessment.
In the seven studies, only 111 children received the low-FODMAP diet, while 85 followed a control diet for comparison (a diet described as healthy, usual, or typical American diet for children).
All of the pediatric studies focused on functional abdominal pain disorders. None addressed nonceliac gluten sensitivity, small-intestinal bacterial overgrowth, or inflammatory bowel disease.
From their review, the authors conclude that, at present, there is “insufficient evidence” to routinely recommend the low-FODMAP diet for the treatment of functional GI disorders, nonceliac gluten sensitivity, inflammatory bowel diseases, or small-intestinal bacterial overgrowth in children.
When the low-FODMAP diet is considered for children, the authors recommend a thorough clinical history, physical examination, and assessment of nutritional status and GI symptoms by a multidisciplinary team.
“Ideally, a standardized questionnaire should be used before and following the start of the diet to assess objectively the effect of the low-FODMAP diet,” the authors advise.
A dietitian should assess the child’s diet to highlight any potential deficiencies, which could be exacerbated by the restrictions of the low-FODMAP diet.
To promote adherence to the diet, potential difficulties, such as how to provide a suitable lunch at school or what to do when the child is staying at a friend’s house, should be addressed.
The authors suggest providing parents with written information about sources of FODMAPs and suitable replacement foods. Offering meal plans can reduce the risk of diet mistakes as well as the risk of offering a diet insufficient in essential nutrients, they say.
‘Useful paper’
“This is a useful paper primarily to outline the paucity of data regarding dietary therapies in children and the importance of doing studies in this population,” Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist with Massachusetts General Hospital and Harvard Medical School, both in Boston, who wasn’t involved in the research, told this news organization.
Samuel Nurko, MD, MPH, director of the Center for Motility and Functional Gastrointestinal Disorders at Boston Children’s Hospital, Massachusetts, noted that some studies have shown that a low-FODMAP diet can be effective in controlling symptoms for both adults and kids.
“The problem in kids is that the trials are very small, and there’s not a lot of them, so the evidence is limited,” said Dr. Nurko, who wasn’t involved in writing the position paper.
That’s not to say that it should not be tried in appropriate cases. “There’s no question that in some patients, taking away the FODMAPs gives them a big improvement in GI symptoms,” Dr. Nurko told this news organization.
“The problem with the low-FODMAP diet is, if you don’t do it right, then you get into trouble with nutritional deficiencies,” he cautioned.
“If you are going to try the low-FODMAP diet, it has to be short, no more than 4-6 weeks, and you need to do a top-down approach. Take FODMAPs out, and then start to reintroduce them. Either kids will respond to the diet, or they won’t. If they don’t, there is no reason to keep them on the diet. It’s a very hard diet to take,” Dr. Nurko said.
No source of funding for the study was disclosed. The authors, Dr. Ananthakrishnan, and Dr. Nurko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
American Academy of Pediatrics recommends adolescent suicide screening
With suicide rates among young people rising in recent years, the American Academy of Pediatrics is now recommending adolescents 12 and up be screened for suicide risk as a part of regular preventive care.
The group recently added the recommendation on screening for suicide risk to its depression screening guidelines. Health care providers are urged to ask their young patients a set of questions to identify thoughts and plans for suicide, WDEF.com reported.
“Number one we need to screen for depression and the presence of depression, and those people will usually have a feeling of depressed mood, hopelessness, helplessness, and/or basically a lack of interest in pleasure or anticipation of happiness,” Timothy Fuller, DO, medical director of behavioral health and pediatrics for the American Academy of Pediatrics, told WDEF.
It’s a myth that talking about suicide makes it more likely a person will attempt suicide, he said.
“One of the biggest things you can do, as well, if you do have a child or teenager that has suicidality or that have depression with serious, significant suicide risk, is to just ask them how they’re doing every day,” Dr. Fuller said, according to WDEF.
The recommendation comes about 6 months after U.S. Surgeon General Vivek Murthy, MD, urged more attention be paid to youth mental health.
“Mental health challenges in children, adolescents, and young adults are real and widespread. Even before the pandemic, an alarming number of young people struggled with feelings of helplessness, depression, and thoughts of suicide – and rates have increased over the past decade,” Dr. Murthy said, according to a news release from the U.S. Department of Health & Human Services.
Between 2007 and 2018, suicide rates among people ages 10-24 in the United States went up by 57%, the department said. Estimates showed over 6,600 suicides among this age group in 2020, it said.
A version of this article first appeared on WebMD.com.
With suicide rates among young people rising in recent years, the American Academy of Pediatrics is now recommending adolescents 12 and up be screened for suicide risk as a part of regular preventive care.
The group recently added the recommendation on screening for suicide risk to its depression screening guidelines. Health care providers are urged to ask their young patients a set of questions to identify thoughts and plans for suicide, WDEF.com reported.
“Number one we need to screen for depression and the presence of depression, and those people will usually have a feeling of depressed mood, hopelessness, helplessness, and/or basically a lack of interest in pleasure or anticipation of happiness,” Timothy Fuller, DO, medical director of behavioral health and pediatrics for the American Academy of Pediatrics, told WDEF.
It’s a myth that talking about suicide makes it more likely a person will attempt suicide, he said.
“One of the biggest things you can do, as well, if you do have a child or teenager that has suicidality or that have depression with serious, significant suicide risk, is to just ask them how they’re doing every day,” Dr. Fuller said, according to WDEF.
The recommendation comes about 6 months after U.S. Surgeon General Vivek Murthy, MD, urged more attention be paid to youth mental health.
“Mental health challenges in children, adolescents, and young adults are real and widespread. Even before the pandemic, an alarming number of young people struggled with feelings of helplessness, depression, and thoughts of suicide – and rates have increased over the past decade,” Dr. Murthy said, according to a news release from the U.S. Department of Health & Human Services.
Between 2007 and 2018, suicide rates among people ages 10-24 in the United States went up by 57%, the department said. Estimates showed over 6,600 suicides among this age group in 2020, it said.
A version of this article first appeared on WebMD.com.
With suicide rates among young people rising in recent years, the American Academy of Pediatrics is now recommending adolescents 12 and up be screened for suicide risk as a part of regular preventive care.
The group recently added the recommendation on screening for suicide risk to its depression screening guidelines. Health care providers are urged to ask their young patients a set of questions to identify thoughts and plans for suicide, WDEF.com reported.
“Number one we need to screen for depression and the presence of depression, and those people will usually have a feeling of depressed mood, hopelessness, helplessness, and/or basically a lack of interest in pleasure or anticipation of happiness,” Timothy Fuller, DO, medical director of behavioral health and pediatrics for the American Academy of Pediatrics, told WDEF.
It’s a myth that talking about suicide makes it more likely a person will attempt suicide, he said.
“One of the biggest things you can do, as well, if you do have a child or teenager that has suicidality or that have depression with serious, significant suicide risk, is to just ask them how they’re doing every day,” Dr. Fuller said, according to WDEF.
The recommendation comes about 6 months after U.S. Surgeon General Vivek Murthy, MD, urged more attention be paid to youth mental health.
“Mental health challenges in children, adolescents, and young adults are real and widespread. Even before the pandemic, an alarming number of young people struggled with feelings of helplessness, depression, and thoughts of suicide – and rates have increased over the past decade,” Dr. Murthy said, according to a news release from the U.S. Department of Health & Human Services.
Between 2007 and 2018, suicide rates among people ages 10-24 in the United States went up by 57%, the department said. Estimates showed over 6,600 suicides among this age group in 2020, it said.
A version of this article first appeared on WebMD.com.
LGBTQ students would get new protections under Biden plan
On the 50th anniversary of Title IX’s inception, the Biden administration has proposed changes to the law that would protect transgender students and assault survivors on college and university campuses.
With these changes, the protections provided by Title IX – a civil rights law that prohibits sex-based discrimination in schools that receive federal funding – would now be extended to students who identify as trans. The update would ensure that government-funded schools make proper accommodations for a trans student population, such as allowing students to use bathrooms and other facilities that align with their gender identity, and enforcing the use of students’ correct pronouns.
The revisions also seek to undo amendments made to the law by Betsy DeVos, who was secretary of education during the Trump presidency, which strengthened due process protections for students accused of sexual assault and narrowed the definition of sexual harassment. These rules “weakened protections for survivors of sexual assault and diminished the promise of an education free from discrimination,” the Biden administration said.
“Our proposed changes will allow us to continue that progress and ensure all our nation’s students – no matter where they live, who they are, or whom they love – can learn, grow, and thrive in school,” Education Secretary Miguel Cardona, PhD, said in a news release. “We welcome public comment on these critical regulations so we can further the Biden-Harris Administration’s mission of creating educational environments free from sex discrimination and sexual violence.”
The revisions will go through a long period of public comment before they are set into law. Still, the proposed changes mark a way forward for trans students who are not explicitly protected under Title IX, and they offer solace to assault survivors who may have felt discouraged to come forward and report under Ms. DeVos’s rules.
“The proposed regulations reflect the [Education] Department’s commitment to give full effect to Title IX, ensuring that no person experiences sex discrimination in education, and that school procedures for addressing complaints of sex discrimination, including sexual violence and other forms of sex-based harassment, are clear, effective, and fair to all involved,” said Catherine Lhamon, JD, assistant secretary for the Education Department’s Office Of Civil Rights.
More specific rules about transgender students’ participation in school sports are still to come.
A version of this article first appeared on WebMD.com.
On the 50th anniversary of Title IX’s inception, the Biden administration has proposed changes to the law that would protect transgender students and assault survivors on college and university campuses.
With these changes, the protections provided by Title IX – a civil rights law that prohibits sex-based discrimination in schools that receive federal funding – would now be extended to students who identify as trans. The update would ensure that government-funded schools make proper accommodations for a trans student population, such as allowing students to use bathrooms and other facilities that align with their gender identity, and enforcing the use of students’ correct pronouns.
The revisions also seek to undo amendments made to the law by Betsy DeVos, who was secretary of education during the Trump presidency, which strengthened due process protections for students accused of sexual assault and narrowed the definition of sexual harassment. These rules “weakened protections for survivors of sexual assault and diminished the promise of an education free from discrimination,” the Biden administration said.
“Our proposed changes will allow us to continue that progress and ensure all our nation’s students – no matter where they live, who they are, or whom they love – can learn, grow, and thrive in school,” Education Secretary Miguel Cardona, PhD, said in a news release. “We welcome public comment on these critical regulations so we can further the Biden-Harris Administration’s mission of creating educational environments free from sex discrimination and sexual violence.”
The revisions will go through a long period of public comment before they are set into law. Still, the proposed changes mark a way forward for trans students who are not explicitly protected under Title IX, and they offer solace to assault survivors who may have felt discouraged to come forward and report under Ms. DeVos’s rules.
“The proposed regulations reflect the [Education] Department’s commitment to give full effect to Title IX, ensuring that no person experiences sex discrimination in education, and that school procedures for addressing complaints of sex discrimination, including sexual violence and other forms of sex-based harassment, are clear, effective, and fair to all involved,” said Catherine Lhamon, JD, assistant secretary for the Education Department’s Office Of Civil Rights.
More specific rules about transgender students’ participation in school sports are still to come.
A version of this article first appeared on WebMD.com.
On the 50th anniversary of Title IX’s inception, the Biden administration has proposed changes to the law that would protect transgender students and assault survivors on college and university campuses.
With these changes, the protections provided by Title IX – a civil rights law that prohibits sex-based discrimination in schools that receive federal funding – would now be extended to students who identify as trans. The update would ensure that government-funded schools make proper accommodations for a trans student population, such as allowing students to use bathrooms and other facilities that align with their gender identity, and enforcing the use of students’ correct pronouns.
The revisions also seek to undo amendments made to the law by Betsy DeVos, who was secretary of education during the Trump presidency, which strengthened due process protections for students accused of sexual assault and narrowed the definition of sexual harassment. These rules “weakened protections for survivors of sexual assault and diminished the promise of an education free from discrimination,” the Biden administration said.
“Our proposed changes will allow us to continue that progress and ensure all our nation’s students – no matter where they live, who they are, or whom they love – can learn, grow, and thrive in school,” Education Secretary Miguel Cardona, PhD, said in a news release. “We welcome public comment on these critical regulations so we can further the Biden-Harris Administration’s mission of creating educational environments free from sex discrimination and sexual violence.”
The revisions will go through a long period of public comment before they are set into law. Still, the proposed changes mark a way forward for trans students who are not explicitly protected under Title IX, and they offer solace to assault survivors who may have felt discouraged to come forward and report under Ms. DeVos’s rules.
“The proposed regulations reflect the [Education] Department’s commitment to give full effect to Title IX, ensuring that no person experiences sex discrimination in education, and that school procedures for addressing complaints of sex discrimination, including sexual violence and other forms of sex-based harassment, are clear, effective, and fair to all involved,” said Catherine Lhamon, JD, assistant secretary for the Education Department’s Office Of Civil Rights.
More specific rules about transgender students’ participation in school sports are still to come.
A version of this article first appeared on WebMD.com.
CDC releases new details on mysterious hepatitis in children
A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.
Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.
On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.
This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.
The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..
Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.
Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)
Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.
There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.
The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”
A version of this article first appeared on Medscape.com.
A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.
Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.
On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.
This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.
The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..
Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.
Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)
Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.
There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.
The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”
A version of this article first appeared on Medscape.com.
A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.
Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.
On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.
This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.
The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..
Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.
Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)
Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.
There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.
The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”
A version of this article first appeared on Medscape.com.
FROM THE MMWR
Novel liver-targeting drug offers hope for AAT deficiency
LONDON – The novel liver-targeting agent fazirsiran has fared well in a small, but significant, study looking at its ability to improve liver histology in adults with alpha-1 antitrypsin (AAT) deficiency.
Not only were serum and liver levels of the aberrant Z-AAT protein decreased, but also reductions in key liver enzymes were observed.
AAT is “a greatly understudied disease,” said study investigator Pavel Strnad, MD, who presented the results of the phase 2 AROAAT-2002 study at a meeting sponsored by the European Association for the Study of the Liver. The results were published simultaneously in the New England Journal of Medicine.
“We have a great candidate drug, but we will only be able to bring this drug into the clinic when we understand the disease much better, and for this I would like to ask all of you for your support,” he said to delegates at the meeting.
There is currently no pharmacological treatment for AAT, observed Emmanuel Tsochatzis, MD, who chaired the late-breaker session during which the study findings were presented.
“It is a rare disease, but it really does affect the patients who have it. So it would be great to have a therapeutic solution for these patients,” said Dr. Tsochatzis in an interview.
Dr. Tsochatzis, who is professor of hepatology and Consultant Hepatologist at the UCL Institute for Liver and Digestive Health, Royal Free Hospital in London, noted that AAT was associated with liver impairment, fibrosis and cirrhosis, and ultimately end-stage liver disease in which the only option for some patients would be a liver transplant.
“It depends on the stage; many patients are not at the stage that they require a liver transplant,” he said. “For those with significant liver disease, not yet at the cirrhosis stage, you might be able to intervene early and prevent them from progressing to needing a liver transplant.”
Dr. Tsochatzis speculated: “If this becomes an approved treatment, it is a breakthrough for patients.”
New hope for AAT deficiency
There is still a long way to go before fazirsiran is anywhere near ready for clinical use, but the early data presented by Dr. Strnad offer a glimpse that a treatment could be on the horizon.
Naturally occurring AAT is produced in the liver and is thought to play a role in protecting against lung damage via its antiprotease activity. However, mutations in the SERPINA1 gene coding for the AAT protein leads to loss-of-function pulmonary disease and gain-of-function liver disease.
“The PI ZZ [proteinase inhibitor ZZ] genotype occurs in about one in 2,500 to 3,500 Caucasians, so actually is pretty common, and a third of them may actually have a clinically significant liver fibrosis,” said Dr. Strnad.
As levels of Z-AAT accumulate in the liver this “presumably causes the liver toxicity,” he observed. So, the thinking is that stopping the production of this mutant protein might help to reduce liver damage and allow the liver to regenerate and repair itself.
Study details
To test out this theory, a phase 2, open-label study was performed in 16 patients with confirmed AAT deficiency, all of whom had the PI ZZ genotype.
Eight patients were treated with fazirsiran, also known as ARO-AAT, for 24 weeks (cohorts 1 and 1b), while the other eight were treated for 48 weeks (cohort 2); cohort 1 (n = 4) and cohort 2 (n = 8) received 200 mg, while cohort 1b (n = 4), which was added during the trial to evaluate dose response, received 100 mg. In all cases, fazirsiran was given as a subcutaneous injection on day 1, day 4, and then every 12 weeks. All patients had biopsies at baseline, then at either 24 weeks (cohorts 1/1b) or 48 weeks (cohort 2).
“We saw a dramatic reduction in Z-AAT both in serum and in liver biopsies,” Dr. Strnad reported. Indeed, reductions in Z-AAT were around 80%-88%, he said, with a median reduction of 83% at week 24 or 48 according to the published paper.
To illustrate the clear results, Dr. Strand showed a sample biopsy slide where globules of Z-AAT present at the initial assessment were “virtually gone after 48 weeks of treatment.”
“The change in the serum and hepatic Z-AAT levels translated into improvement in liver function tests,” said Dr. Strnad.
Alanine aminotransferase levels were normalized in all patients and there was “marked improvement” in gamma glutamyl transferase (GGT) with the 200-mg dose of fazirsiran. Substantial changes in liver stiffness were recorded with the higher dose, –18% at 24 weeks and –15% at 48 weeks. There were also reductions in serum Pro-C3 of –36% and –17% at 52 weeks.
“Histological changes showed an improvement in liver inflammation and hepatocyte cell death in most of the patients,” Dr. Strnad said. He also noted that there were multiple cases where there was no change and a few where there was a deterioration.
Liver fibrosis was improved in seven of 12 patients given the highest dose of fazirsiran; however, there was no change in three patients and a worsening of 1 point or more in two patients. None of the three patients with evaluable biopsies who received 100 mg showed regression of fibrosis.
Stopping or rolling back fibrosis will be the final goal of proving clinical benefit in liver disease associated with AAT, Dr. Strnad and coinvestigators observe in their published paper, and while the changes seen so far with fazirsiran may not be uniform, they appear to be in the right direction.
Safety findings
”We didn’t see any drug discontinuation, dose interruption, or premature study withdrawals,” said Dr. Strnad.
“We had four different SAE [serious adverse events] which were kind of all over the place and did not seem to be related to treatment.” Those SAEs included viral myocarditis associated with Epstein-Barr virus infection, diverticulitis, dyspnea in a subject with a history of lung disease, and vestibular neuronitis after COVID-19 vaccination.
No significant safety signals were seen regarding lung function. Time will of course tell, he said in response to a question, but “our hope, our hypothesis, is that this will not change lung function dramatically.
“I would not expect any major things over a few years. Of course, whether this can lead to something over 20 years it is difficult to say.”
The current experience with fazirsiran looks good so far, but placebo-controlled, larger and longer studies are needed.
The study was funded by Arrowhead Pharmaceuticals. Dr. Strnad was an investigator in the study and acknowledged receipt of research funding via his institution from the company. Dr. Strnad also acknowledged paid and unpaid relationships with Alnylam Pharmaceuticals, Alpha1 Deutschland, Alpha1 Global, CSL Behring, Grifols Biologicals, Ono Pharmaceuticals, and Takeda California. Dr. Tsochatzis, chaired the late-breaker session at ILC 2022 during which the study findings were presented, was not connected to the study, and reported no relevant conflicts of interest.
LONDON – The novel liver-targeting agent fazirsiran has fared well in a small, but significant, study looking at its ability to improve liver histology in adults with alpha-1 antitrypsin (AAT) deficiency.
Not only were serum and liver levels of the aberrant Z-AAT protein decreased, but also reductions in key liver enzymes were observed.
AAT is “a greatly understudied disease,” said study investigator Pavel Strnad, MD, who presented the results of the phase 2 AROAAT-2002 study at a meeting sponsored by the European Association for the Study of the Liver. The results were published simultaneously in the New England Journal of Medicine.
“We have a great candidate drug, but we will only be able to bring this drug into the clinic when we understand the disease much better, and for this I would like to ask all of you for your support,” he said to delegates at the meeting.
There is currently no pharmacological treatment for AAT, observed Emmanuel Tsochatzis, MD, who chaired the late-breaker session during which the study findings were presented.
“It is a rare disease, but it really does affect the patients who have it. So it would be great to have a therapeutic solution for these patients,” said Dr. Tsochatzis in an interview.
Dr. Tsochatzis, who is professor of hepatology and Consultant Hepatologist at the UCL Institute for Liver and Digestive Health, Royal Free Hospital in London, noted that AAT was associated with liver impairment, fibrosis and cirrhosis, and ultimately end-stage liver disease in which the only option for some patients would be a liver transplant.
“It depends on the stage; many patients are not at the stage that they require a liver transplant,” he said. “For those with significant liver disease, not yet at the cirrhosis stage, you might be able to intervene early and prevent them from progressing to needing a liver transplant.”
Dr. Tsochatzis speculated: “If this becomes an approved treatment, it is a breakthrough for patients.”
New hope for AAT deficiency
There is still a long way to go before fazirsiran is anywhere near ready for clinical use, but the early data presented by Dr. Strnad offer a glimpse that a treatment could be on the horizon.
Naturally occurring AAT is produced in the liver and is thought to play a role in protecting against lung damage via its antiprotease activity. However, mutations in the SERPINA1 gene coding for the AAT protein leads to loss-of-function pulmonary disease and gain-of-function liver disease.
“The PI ZZ [proteinase inhibitor ZZ] genotype occurs in about one in 2,500 to 3,500 Caucasians, so actually is pretty common, and a third of them may actually have a clinically significant liver fibrosis,” said Dr. Strnad.
As levels of Z-AAT accumulate in the liver this “presumably causes the liver toxicity,” he observed. So, the thinking is that stopping the production of this mutant protein might help to reduce liver damage and allow the liver to regenerate and repair itself.
Study details
To test out this theory, a phase 2, open-label study was performed in 16 patients with confirmed AAT deficiency, all of whom had the PI ZZ genotype.
Eight patients were treated with fazirsiran, also known as ARO-AAT, for 24 weeks (cohorts 1 and 1b), while the other eight were treated for 48 weeks (cohort 2); cohort 1 (n = 4) and cohort 2 (n = 8) received 200 mg, while cohort 1b (n = 4), which was added during the trial to evaluate dose response, received 100 mg. In all cases, fazirsiran was given as a subcutaneous injection on day 1, day 4, and then every 12 weeks. All patients had biopsies at baseline, then at either 24 weeks (cohorts 1/1b) or 48 weeks (cohort 2).
“We saw a dramatic reduction in Z-AAT both in serum and in liver biopsies,” Dr. Strnad reported. Indeed, reductions in Z-AAT were around 80%-88%, he said, with a median reduction of 83% at week 24 or 48 according to the published paper.
To illustrate the clear results, Dr. Strand showed a sample biopsy slide where globules of Z-AAT present at the initial assessment were “virtually gone after 48 weeks of treatment.”
“The change in the serum and hepatic Z-AAT levels translated into improvement in liver function tests,” said Dr. Strnad.
Alanine aminotransferase levels were normalized in all patients and there was “marked improvement” in gamma glutamyl transferase (GGT) with the 200-mg dose of fazirsiran. Substantial changes in liver stiffness were recorded with the higher dose, –18% at 24 weeks and –15% at 48 weeks. There were also reductions in serum Pro-C3 of –36% and –17% at 52 weeks.
“Histological changes showed an improvement in liver inflammation and hepatocyte cell death in most of the patients,” Dr. Strnad said. He also noted that there were multiple cases where there was no change and a few where there was a deterioration.
Liver fibrosis was improved in seven of 12 patients given the highest dose of fazirsiran; however, there was no change in three patients and a worsening of 1 point or more in two patients. None of the three patients with evaluable biopsies who received 100 mg showed regression of fibrosis.
Stopping or rolling back fibrosis will be the final goal of proving clinical benefit in liver disease associated with AAT, Dr. Strnad and coinvestigators observe in their published paper, and while the changes seen so far with fazirsiran may not be uniform, they appear to be in the right direction.
Safety findings
”We didn’t see any drug discontinuation, dose interruption, or premature study withdrawals,” said Dr. Strnad.
“We had four different SAE [serious adverse events] which were kind of all over the place and did not seem to be related to treatment.” Those SAEs included viral myocarditis associated with Epstein-Barr virus infection, diverticulitis, dyspnea in a subject with a history of lung disease, and vestibular neuronitis after COVID-19 vaccination.
No significant safety signals were seen regarding lung function. Time will of course tell, he said in response to a question, but “our hope, our hypothesis, is that this will not change lung function dramatically.
“I would not expect any major things over a few years. Of course, whether this can lead to something over 20 years it is difficult to say.”
The current experience with fazirsiran looks good so far, but placebo-controlled, larger and longer studies are needed.
The study was funded by Arrowhead Pharmaceuticals. Dr. Strnad was an investigator in the study and acknowledged receipt of research funding via his institution from the company. Dr. Strnad also acknowledged paid and unpaid relationships with Alnylam Pharmaceuticals, Alpha1 Deutschland, Alpha1 Global, CSL Behring, Grifols Biologicals, Ono Pharmaceuticals, and Takeda California. Dr. Tsochatzis, chaired the late-breaker session at ILC 2022 during which the study findings were presented, was not connected to the study, and reported no relevant conflicts of interest.
LONDON – The novel liver-targeting agent fazirsiran has fared well in a small, but significant, study looking at its ability to improve liver histology in adults with alpha-1 antitrypsin (AAT) deficiency.
Not only were serum and liver levels of the aberrant Z-AAT protein decreased, but also reductions in key liver enzymes were observed.
AAT is “a greatly understudied disease,” said study investigator Pavel Strnad, MD, who presented the results of the phase 2 AROAAT-2002 study at a meeting sponsored by the European Association for the Study of the Liver. The results were published simultaneously in the New England Journal of Medicine.
“We have a great candidate drug, but we will only be able to bring this drug into the clinic when we understand the disease much better, and for this I would like to ask all of you for your support,” he said to delegates at the meeting.
There is currently no pharmacological treatment for AAT, observed Emmanuel Tsochatzis, MD, who chaired the late-breaker session during which the study findings were presented.
“It is a rare disease, but it really does affect the patients who have it. So it would be great to have a therapeutic solution for these patients,” said Dr. Tsochatzis in an interview.
Dr. Tsochatzis, who is professor of hepatology and Consultant Hepatologist at the UCL Institute for Liver and Digestive Health, Royal Free Hospital in London, noted that AAT was associated with liver impairment, fibrosis and cirrhosis, and ultimately end-stage liver disease in which the only option for some patients would be a liver transplant.
“It depends on the stage; many patients are not at the stage that they require a liver transplant,” he said. “For those with significant liver disease, not yet at the cirrhosis stage, you might be able to intervene early and prevent them from progressing to needing a liver transplant.”
Dr. Tsochatzis speculated: “If this becomes an approved treatment, it is a breakthrough for patients.”
New hope for AAT deficiency
There is still a long way to go before fazirsiran is anywhere near ready for clinical use, but the early data presented by Dr. Strnad offer a glimpse that a treatment could be on the horizon.
Naturally occurring AAT is produced in the liver and is thought to play a role in protecting against lung damage via its antiprotease activity. However, mutations in the SERPINA1 gene coding for the AAT protein leads to loss-of-function pulmonary disease and gain-of-function liver disease.
“The PI ZZ [proteinase inhibitor ZZ] genotype occurs in about one in 2,500 to 3,500 Caucasians, so actually is pretty common, and a third of them may actually have a clinically significant liver fibrosis,” said Dr. Strnad.
As levels of Z-AAT accumulate in the liver this “presumably causes the liver toxicity,” he observed. So, the thinking is that stopping the production of this mutant protein might help to reduce liver damage and allow the liver to regenerate and repair itself.
Study details
To test out this theory, a phase 2, open-label study was performed in 16 patients with confirmed AAT deficiency, all of whom had the PI ZZ genotype.
Eight patients were treated with fazirsiran, also known as ARO-AAT, for 24 weeks (cohorts 1 and 1b), while the other eight were treated for 48 weeks (cohort 2); cohort 1 (n = 4) and cohort 2 (n = 8) received 200 mg, while cohort 1b (n = 4), which was added during the trial to evaluate dose response, received 100 mg. In all cases, fazirsiran was given as a subcutaneous injection on day 1, day 4, and then every 12 weeks. All patients had biopsies at baseline, then at either 24 weeks (cohorts 1/1b) or 48 weeks (cohort 2).
“We saw a dramatic reduction in Z-AAT both in serum and in liver biopsies,” Dr. Strnad reported. Indeed, reductions in Z-AAT were around 80%-88%, he said, with a median reduction of 83% at week 24 or 48 according to the published paper.
To illustrate the clear results, Dr. Strand showed a sample biopsy slide where globules of Z-AAT present at the initial assessment were “virtually gone after 48 weeks of treatment.”
“The change in the serum and hepatic Z-AAT levels translated into improvement in liver function tests,” said Dr. Strnad.
Alanine aminotransferase levels were normalized in all patients and there was “marked improvement” in gamma glutamyl transferase (GGT) with the 200-mg dose of fazirsiran. Substantial changes in liver stiffness were recorded with the higher dose, –18% at 24 weeks and –15% at 48 weeks. There were also reductions in serum Pro-C3 of –36% and –17% at 52 weeks.
“Histological changes showed an improvement in liver inflammation and hepatocyte cell death in most of the patients,” Dr. Strnad said. He also noted that there were multiple cases where there was no change and a few where there was a deterioration.
Liver fibrosis was improved in seven of 12 patients given the highest dose of fazirsiran; however, there was no change in three patients and a worsening of 1 point or more in two patients. None of the three patients with evaluable biopsies who received 100 mg showed regression of fibrosis.
Stopping or rolling back fibrosis will be the final goal of proving clinical benefit in liver disease associated with AAT, Dr. Strnad and coinvestigators observe in their published paper, and while the changes seen so far with fazirsiran may not be uniform, they appear to be in the right direction.
Safety findings
”We didn’t see any drug discontinuation, dose interruption, or premature study withdrawals,” said Dr. Strnad.
“We had four different SAE [serious adverse events] which were kind of all over the place and did not seem to be related to treatment.” Those SAEs included viral myocarditis associated with Epstein-Barr virus infection, diverticulitis, dyspnea in a subject with a history of lung disease, and vestibular neuronitis after COVID-19 vaccination.
No significant safety signals were seen regarding lung function. Time will of course tell, he said in response to a question, but “our hope, our hypothesis, is that this will not change lung function dramatically.
“I would not expect any major things over a few years. Of course, whether this can lead to something over 20 years it is difficult to say.”
The current experience with fazirsiran looks good so far, but placebo-controlled, larger and longer studies are needed.
The study was funded by Arrowhead Pharmaceuticals. Dr. Strnad was an investigator in the study and acknowledged receipt of research funding via his institution from the company. Dr. Strnad also acknowledged paid and unpaid relationships with Alnylam Pharmaceuticals, Alpha1 Deutschland, Alpha1 Global, CSL Behring, Grifols Biologicals, Ono Pharmaceuticals, and Takeda California. Dr. Tsochatzis, chaired the late-breaker session at ILC 2022 during which the study findings were presented, was not connected to the study, and reported no relevant conflicts of interest.
AT ILC 2022
Both parents at risk for depression following birth
Physicians have screened new and expectant mothers for perinatal depression for years. But what about fathers?
A new systematic review and meta-analysis suggests it’s time for health care providers to ask both parents about any mental health symptoms before and after their baby is born.
“We are screening most mothers for signs of perinatal depression,” said Kara Smythe, MD, at the department of primary care and population health and Institute of Epidemiology and Health Care at the University College London, who is the lead author of the study. “But we aren’t always asking about the relationship between them and the person helping them care for this newborn. If we don’t consider the experience of new fathers, we’re doing a disservice to everyone.”
Without screening both parents, health care providers can miss important clues to why child and parents experience adverse health outcomes post birth.
The study, published in JAMA Network Open, found that for 3.18% of couples, both parents concurrently experienced depression before and following a birth. The mental illness was more common in the late postnatal period (3-12 months).
According to the Centers for Disease Control and Prevention, about 1 in 8 women experience symptoms of postpartum depression. Other sources indicate the incidence may be much higher. Findings from a mobile app using the Edinburgh Postnatal Depression Scale presented at the American Psychiatric Association’s annual meeting in 2019 indicated more than half of the 164,237 women who used the free app reported symptoms of depression for up to a year following the birth of their baby.
The findings
Dr. Smythe and her team reviewed previously published observational studies on the prevalence of perinatal depression or anxiety in couples from the Ovid and Web of Science between Jan. 1, 1990, and June 8, 2021.
They ultimately included 23 studies with data from 29,286 couples. They broke the data into subgroups of persons with antenatal depression, early postnatal depression (0-12 weeks), late postnatal depression (3-13 months), and perinatal anxiety.
About 1.7% (P < .001) of couples experienced antenatal depression, and about 2.4% (P < .001) experienced early postnatal depression. About 3.2% (P < .001) experienced late postnatal depression. The data on perinatal anxiety were insufficient, they write.
The vast majority of couples included in the samples were White, heterosexual, and highly educated with a middle to high socioeconomic background. The pregnancies were reportedly wanted, if not planned. The majority of the studies – 21 – included in the analysis were from countries other than the United States.
According to the study, evidence suggests that paternal depression can lead to increased symptoms of depression in mothers during pregnancy and the following 6 months. Men reported perinatal depression at similar rates as women, and Dr. Smythe said it’s becoming clear that men experience similar struggles as they transition into fatherhood.
J. J. Parker, MD, a pediatric and internal attending physician at Lurie Children’s Hospital of Chicago and Northwestern Medicine, said the findings solidify what he has observed from his own experience as a new father and resident.
“You’re at higher risk of having depression if your partner has depression, but it’s important to see that in the numbers,” Dr. Parker told this news organization. “I think from a clinician standpoint, this demonstrates that 3% of infants are living in households where both parents are depressed, and that has major implications for the development and health of those children.”
Dr. Smythe and her colleagues found that if even one parent is experiencing a mood disorder such as depression or anxiety, the newborn can experience impaired bonding, behavioral problems, and other harms later in life.
If both parents are experiencing perinatal depression, those negative outcomes could be amplified, although Dr. Smythe said more research is needed to solidify the link.
“I think one quick takeaway for pediatricians, clinicians, and any other health care providers taking care of mothers and infants is to ask about the nonbirthing parent,” Dr. Parker said. “All clinicians can do that right away, even if the mother does not have depression.”
The study was independently supported. Dr. Smythe and her colleagues report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians have screened new and expectant mothers for perinatal depression for years. But what about fathers?
A new systematic review and meta-analysis suggests it’s time for health care providers to ask both parents about any mental health symptoms before and after their baby is born.
“We are screening most mothers for signs of perinatal depression,” said Kara Smythe, MD, at the department of primary care and population health and Institute of Epidemiology and Health Care at the University College London, who is the lead author of the study. “But we aren’t always asking about the relationship between them and the person helping them care for this newborn. If we don’t consider the experience of new fathers, we’re doing a disservice to everyone.”
Without screening both parents, health care providers can miss important clues to why child and parents experience adverse health outcomes post birth.
The study, published in JAMA Network Open, found that for 3.18% of couples, both parents concurrently experienced depression before and following a birth. The mental illness was more common in the late postnatal period (3-12 months).
According to the Centers for Disease Control and Prevention, about 1 in 8 women experience symptoms of postpartum depression. Other sources indicate the incidence may be much higher. Findings from a mobile app using the Edinburgh Postnatal Depression Scale presented at the American Psychiatric Association’s annual meeting in 2019 indicated more than half of the 164,237 women who used the free app reported symptoms of depression for up to a year following the birth of their baby.
The findings
Dr. Smythe and her team reviewed previously published observational studies on the prevalence of perinatal depression or anxiety in couples from the Ovid and Web of Science between Jan. 1, 1990, and June 8, 2021.
They ultimately included 23 studies with data from 29,286 couples. They broke the data into subgroups of persons with antenatal depression, early postnatal depression (0-12 weeks), late postnatal depression (3-13 months), and perinatal anxiety.
About 1.7% (P < .001) of couples experienced antenatal depression, and about 2.4% (P < .001) experienced early postnatal depression. About 3.2% (P < .001) experienced late postnatal depression. The data on perinatal anxiety were insufficient, they write.
The vast majority of couples included in the samples were White, heterosexual, and highly educated with a middle to high socioeconomic background. The pregnancies were reportedly wanted, if not planned. The majority of the studies – 21 – included in the analysis were from countries other than the United States.
According to the study, evidence suggests that paternal depression can lead to increased symptoms of depression in mothers during pregnancy and the following 6 months. Men reported perinatal depression at similar rates as women, and Dr. Smythe said it’s becoming clear that men experience similar struggles as they transition into fatherhood.
J. J. Parker, MD, a pediatric and internal attending physician at Lurie Children’s Hospital of Chicago and Northwestern Medicine, said the findings solidify what he has observed from his own experience as a new father and resident.
“You’re at higher risk of having depression if your partner has depression, but it’s important to see that in the numbers,” Dr. Parker told this news organization. “I think from a clinician standpoint, this demonstrates that 3% of infants are living in households where both parents are depressed, and that has major implications for the development and health of those children.”
Dr. Smythe and her colleagues found that if even one parent is experiencing a mood disorder such as depression or anxiety, the newborn can experience impaired bonding, behavioral problems, and other harms later in life.
If both parents are experiencing perinatal depression, those negative outcomes could be amplified, although Dr. Smythe said more research is needed to solidify the link.
“I think one quick takeaway for pediatricians, clinicians, and any other health care providers taking care of mothers and infants is to ask about the nonbirthing parent,” Dr. Parker said. “All clinicians can do that right away, even if the mother does not have depression.”
The study was independently supported. Dr. Smythe and her colleagues report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians have screened new and expectant mothers for perinatal depression for years. But what about fathers?
A new systematic review and meta-analysis suggests it’s time for health care providers to ask both parents about any mental health symptoms before and after their baby is born.
“We are screening most mothers for signs of perinatal depression,” said Kara Smythe, MD, at the department of primary care and population health and Institute of Epidemiology and Health Care at the University College London, who is the lead author of the study. “But we aren’t always asking about the relationship between them and the person helping them care for this newborn. If we don’t consider the experience of new fathers, we’re doing a disservice to everyone.”
Without screening both parents, health care providers can miss important clues to why child and parents experience adverse health outcomes post birth.
The study, published in JAMA Network Open, found that for 3.18% of couples, both parents concurrently experienced depression before and following a birth. The mental illness was more common in the late postnatal period (3-12 months).
According to the Centers for Disease Control and Prevention, about 1 in 8 women experience symptoms of postpartum depression. Other sources indicate the incidence may be much higher. Findings from a mobile app using the Edinburgh Postnatal Depression Scale presented at the American Psychiatric Association’s annual meeting in 2019 indicated more than half of the 164,237 women who used the free app reported symptoms of depression for up to a year following the birth of their baby.
The findings
Dr. Smythe and her team reviewed previously published observational studies on the prevalence of perinatal depression or anxiety in couples from the Ovid and Web of Science between Jan. 1, 1990, and June 8, 2021.
They ultimately included 23 studies with data from 29,286 couples. They broke the data into subgroups of persons with antenatal depression, early postnatal depression (0-12 weeks), late postnatal depression (3-13 months), and perinatal anxiety.
About 1.7% (P < .001) of couples experienced antenatal depression, and about 2.4% (P < .001) experienced early postnatal depression. About 3.2% (P < .001) experienced late postnatal depression. The data on perinatal anxiety were insufficient, they write.
The vast majority of couples included in the samples were White, heterosexual, and highly educated with a middle to high socioeconomic background. The pregnancies were reportedly wanted, if not planned. The majority of the studies – 21 – included in the analysis were from countries other than the United States.
According to the study, evidence suggests that paternal depression can lead to increased symptoms of depression in mothers during pregnancy and the following 6 months. Men reported perinatal depression at similar rates as women, and Dr. Smythe said it’s becoming clear that men experience similar struggles as they transition into fatherhood.
J. J. Parker, MD, a pediatric and internal attending physician at Lurie Children’s Hospital of Chicago and Northwestern Medicine, said the findings solidify what he has observed from his own experience as a new father and resident.
“You’re at higher risk of having depression if your partner has depression, but it’s important to see that in the numbers,” Dr. Parker told this news organization. “I think from a clinician standpoint, this demonstrates that 3% of infants are living in households where both parents are depressed, and that has major implications for the development and health of those children.”
Dr. Smythe and her colleagues found that if even one parent is experiencing a mood disorder such as depression or anxiety, the newborn can experience impaired bonding, behavioral problems, and other harms later in life.
If both parents are experiencing perinatal depression, those negative outcomes could be amplified, although Dr. Smythe said more research is needed to solidify the link.
“I think one quick takeaway for pediatricians, clinicians, and any other health care providers taking care of mothers and infants is to ask about the nonbirthing parent,” Dr. Parker said. “All clinicians can do that right away, even if the mother does not have depression.”
The study was independently supported. Dr. Smythe and her colleagues report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Women benefit but lag behind in intracoronary imaging in PCI
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR INTERVENTIONS