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Coding variants in apolipoprotein B may be associated with early-onset Alzheimer’s disease
Variants in the apolipoprotein B gene (APOB), which creates the main protein in low-density and very low-density cholesterol, may be associated with early-onset Alzheimer’s disease, Thomas Wingo, MD, and his colleagues have determined.
The finding may help fill out the genetic risk picture for early-onset Alzheimer’s disease (EOAD), said Dr. Wingo of the Atlanta Veterans Affairs Medical Center. The study found that the already-known genetic markers for EOAD – mutations of the presenilin (PSEN) 1 and 2 genes and amyloid precursor protein (APP) – account for just a small fraction of cases.
“To place the genetic association between APOB and EOAD in context, we note that only 3.4% of all EOAD cases in our combined data set showed a known pathogenic mutation, and we found a stronger association between EOAD and rare coding variants in APOB, compared with PSEN1 in our fully adjusted analysis,” the team wrote. However, “approximately 5.0% of patients with EOAD and 1.7% of controls were found to harbor a rare coding polymorphism in APOB that is likely to disrupt the structure, functions, or abundance of ApoB protein.”
The team conducted genetic analysis on plasma samples from 2,125 EOAD and control subjects included in several research cohorts. They first determined the association between cholesterol and EOAD, and then the frequency of variants in apolipoprotein E epsilon 4 (APOE e4), APP, PSEN1, PSEN2, and ApoB. Gene sequencing revealed that 3.4% of samples showed mutations in APP, PSEN1, or PSEN2.
“Given the strong associations between APOE e4 and EOAD and elevated circulating LDL cholesterol levels, we expected individuals with EOAD to have elevated LDL levels,” the team said. But an analysis of 267 of the samples for lipid levels found that, even after the researchers controlled for APOE e4, EOAD cases had higher total cholesterol, low-density cholesterol, and plasma ApoB, compared with controls. However, they found no association between EOAD and high-density lipoprotein or triglycerides.
“Because total cholesterol largely consists of LDL-C, and ApoB is the main lipoprotein of LDL-C, these findings are consistent with one another.
“From these data, we estimated that LDL-C explains 7.6% of the variance in liability to EOAD, independently of APOE e4 ... These results demonstrate that elevated levels of LDL-C [and ApoB] were significantly associated with increased EOAD risk, and this effect was only partially mediated by APOE e4 genotype.”
The results also raised a question: What was driving the association between LDL and EOAD? Because variants of the ApoB gene can either raise or lower LDL, the team examined variants associated with coding changes. These variants were significantly more common in EOAD cases than in controls (5.0% vs. 1.7%).
“Two affected individuals ... were compound heterozygotes, with the remainder being heterozygotes,” the researchers wrote. “Each compound heterozygote case was heterozygous for two different rare coding sites ... Of these four variants, only [one] has been previously described.”
“Our finding of a significant association between rare coding variants in APOB and EOAD independently of APOE is novel, important, and consistent with multiple genome-wide association studies that revealed strong associations between late-onset AD and common intron markers of genes involved in brain cholesterol metabolism [ABCA7, BIN1, CLU, and SORL1]. Furthermore, mice overexpressing ApoB show hyperlipidemia, neurodegeneration, increases in APP, accumulation of amyloid plaques, and cognitive impairment similar to mice overexpressing wild-type human APP. Collectively, these studies and our findings suggest an important role of cholesterol metabolism in AD pathogenesis.”
This research was supported by grants from the Veterans Health Administration, the National Institutes of Health, the To Remember Foundation, the Douglas French Alzheimer’s Foundation, and a contract with the State of California Department of Health Services. Several authors reported financial ties to pharmaceutical companies outside of this work.
SOURCE: Wingo TS et al. JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0648.
This important study provides the first evidence that rare genetic coding variants of apolipoprotein B may contribute to the risk of early-onset Alzheimer’s disease, Makoto Ishii, MD, PhD, wrote in an accompanying editorial (JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0212).
But the study by Wingo et al. doesn’t tell the entire tale, he wrote.
The results from this study “found that there are likely to be additional contributing factors independent of APOB and APOE. These may include rare variants in other genes involved directly in LDL cholesterol metabolism, such as the LDL receptor and proprotein convertase subtilisin/kexin type 913 or factors known to modulate circulating LDL cholesterol levels, such as thyroid hormones.”
Although intriguing, “Clearly, additional studies looking at these factors are needed to fully elucidate the association between LDL cholesterol and EOAD. Furthermore, as the authors of this study note, it is not known if there are protective variants of APOB that would decrease the risk for developing EOAD. Identifying such a protective coding variant of APOB would greatly strengthen the link between APOB and AD pathogenesis.”
Prior studies of circulating APOB levels in humans have reached disparate conclusions. A large population-based study found no association between APOB levels and incident dementia or Alzheimer’s, he noted.
“Therefore, whether these findings can be verified in individuals with late-onset AD remains to be determined.”
Dr. Ishii is with the Feil Family Brain and Mind Research Institute in the department of neurology at Cornell University, New York. He has no relevant disclosures.
This important study provides the first evidence that rare genetic coding variants of apolipoprotein B may contribute to the risk of early-onset Alzheimer’s disease, Makoto Ishii, MD, PhD, wrote in an accompanying editorial (JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0212).
But the study by Wingo et al. doesn’t tell the entire tale, he wrote.
The results from this study “found that there are likely to be additional contributing factors independent of APOB and APOE. These may include rare variants in other genes involved directly in LDL cholesterol metabolism, such as the LDL receptor and proprotein convertase subtilisin/kexin type 913 or factors known to modulate circulating LDL cholesterol levels, such as thyroid hormones.”
Although intriguing, “Clearly, additional studies looking at these factors are needed to fully elucidate the association between LDL cholesterol and EOAD. Furthermore, as the authors of this study note, it is not known if there are protective variants of APOB that would decrease the risk for developing EOAD. Identifying such a protective coding variant of APOB would greatly strengthen the link between APOB and AD pathogenesis.”
Prior studies of circulating APOB levels in humans have reached disparate conclusions. A large population-based study found no association between APOB levels and incident dementia or Alzheimer’s, he noted.
“Therefore, whether these findings can be verified in individuals with late-onset AD remains to be determined.”
Dr. Ishii is with the Feil Family Brain and Mind Research Institute in the department of neurology at Cornell University, New York. He has no relevant disclosures.
This important study provides the first evidence that rare genetic coding variants of apolipoprotein B may contribute to the risk of early-onset Alzheimer’s disease, Makoto Ishii, MD, PhD, wrote in an accompanying editorial (JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0212).
But the study by Wingo et al. doesn’t tell the entire tale, he wrote.
The results from this study “found that there are likely to be additional contributing factors independent of APOB and APOE. These may include rare variants in other genes involved directly in LDL cholesterol metabolism, such as the LDL receptor and proprotein convertase subtilisin/kexin type 913 or factors known to modulate circulating LDL cholesterol levels, such as thyroid hormones.”
Although intriguing, “Clearly, additional studies looking at these factors are needed to fully elucidate the association between LDL cholesterol and EOAD. Furthermore, as the authors of this study note, it is not known if there are protective variants of APOB that would decrease the risk for developing EOAD. Identifying such a protective coding variant of APOB would greatly strengthen the link between APOB and AD pathogenesis.”
Prior studies of circulating APOB levels in humans have reached disparate conclusions. A large population-based study found no association between APOB levels and incident dementia or Alzheimer’s, he noted.
“Therefore, whether these findings can be verified in individuals with late-onset AD remains to be determined.”
Dr. Ishii is with the Feil Family Brain and Mind Research Institute in the department of neurology at Cornell University, New York. He has no relevant disclosures.
Variants in the apolipoprotein B gene (APOB), which creates the main protein in low-density and very low-density cholesterol, may be associated with early-onset Alzheimer’s disease, Thomas Wingo, MD, and his colleagues have determined.
The finding may help fill out the genetic risk picture for early-onset Alzheimer’s disease (EOAD), said Dr. Wingo of the Atlanta Veterans Affairs Medical Center. The study found that the already-known genetic markers for EOAD – mutations of the presenilin (PSEN) 1 and 2 genes and amyloid precursor protein (APP) – account for just a small fraction of cases.
“To place the genetic association between APOB and EOAD in context, we note that only 3.4% of all EOAD cases in our combined data set showed a known pathogenic mutation, and we found a stronger association between EOAD and rare coding variants in APOB, compared with PSEN1 in our fully adjusted analysis,” the team wrote. However, “approximately 5.0% of patients with EOAD and 1.7% of controls were found to harbor a rare coding polymorphism in APOB that is likely to disrupt the structure, functions, or abundance of ApoB protein.”
The team conducted genetic analysis on plasma samples from 2,125 EOAD and control subjects included in several research cohorts. They first determined the association between cholesterol and EOAD, and then the frequency of variants in apolipoprotein E epsilon 4 (APOE e4), APP, PSEN1, PSEN2, and ApoB. Gene sequencing revealed that 3.4% of samples showed mutations in APP, PSEN1, or PSEN2.
“Given the strong associations between APOE e4 and EOAD and elevated circulating LDL cholesterol levels, we expected individuals with EOAD to have elevated LDL levels,” the team said. But an analysis of 267 of the samples for lipid levels found that, even after the researchers controlled for APOE e4, EOAD cases had higher total cholesterol, low-density cholesterol, and plasma ApoB, compared with controls. However, they found no association between EOAD and high-density lipoprotein or triglycerides.
“Because total cholesterol largely consists of LDL-C, and ApoB is the main lipoprotein of LDL-C, these findings are consistent with one another.
“From these data, we estimated that LDL-C explains 7.6% of the variance in liability to EOAD, independently of APOE e4 ... These results demonstrate that elevated levels of LDL-C [and ApoB] were significantly associated with increased EOAD risk, and this effect was only partially mediated by APOE e4 genotype.”
The results also raised a question: What was driving the association between LDL and EOAD? Because variants of the ApoB gene can either raise or lower LDL, the team examined variants associated with coding changes. These variants were significantly more common in EOAD cases than in controls (5.0% vs. 1.7%).
“Two affected individuals ... were compound heterozygotes, with the remainder being heterozygotes,” the researchers wrote. “Each compound heterozygote case was heterozygous for two different rare coding sites ... Of these four variants, only [one] has been previously described.”
“Our finding of a significant association between rare coding variants in APOB and EOAD independently of APOE is novel, important, and consistent with multiple genome-wide association studies that revealed strong associations between late-onset AD and common intron markers of genes involved in brain cholesterol metabolism [ABCA7, BIN1, CLU, and SORL1]. Furthermore, mice overexpressing ApoB show hyperlipidemia, neurodegeneration, increases in APP, accumulation of amyloid plaques, and cognitive impairment similar to mice overexpressing wild-type human APP. Collectively, these studies and our findings suggest an important role of cholesterol metabolism in AD pathogenesis.”
This research was supported by grants from the Veterans Health Administration, the National Institutes of Health, the To Remember Foundation, the Douglas French Alzheimer’s Foundation, and a contract with the State of California Department of Health Services. Several authors reported financial ties to pharmaceutical companies outside of this work.
SOURCE: Wingo TS et al. JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0648.
Variants in the apolipoprotein B gene (APOB), which creates the main protein in low-density and very low-density cholesterol, may be associated with early-onset Alzheimer’s disease, Thomas Wingo, MD, and his colleagues have determined.
The finding may help fill out the genetic risk picture for early-onset Alzheimer’s disease (EOAD), said Dr. Wingo of the Atlanta Veterans Affairs Medical Center. The study found that the already-known genetic markers for EOAD – mutations of the presenilin (PSEN) 1 and 2 genes and amyloid precursor protein (APP) – account for just a small fraction of cases.
“To place the genetic association between APOB and EOAD in context, we note that only 3.4% of all EOAD cases in our combined data set showed a known pathogenic mutation, and we found a stronger association between EOAD and rare coding variants in APOB, compared with PSEN1 in our fully adjusted analysis,” the team wrote. However, “approximately 5.0% of patients with EOAD and 1.7% of controls were found to harbor a rare coding polymorphism in APOB that is likely to disrupt the structure, functions, or abundance of ApoB protein.”
The team conducted genetic analysis on plasma samples from 2,125 EOAD and control subjects included in several research cohorts. They first determined the association between cholesterol and EOAD, and then the frequency of variants in apolipoprotein E epsilon 4 (APOE e4), APP, PSEN1, PSEN2, and ApoB. Gene sequencing revealed that 3.4% of samples showed mutations in APP, PSEN1, or PSEN2.
“Given the strong associations between APOE e4 and EOAD and elevated circulating LDL cholesterol levels, we expected individuals with EOAD to have elevated LDL levels,” the team said. But an analysis of 267 of the samples for lipid levels found that, even after the researchers controlled for APOE e4, EOAD cases had higher total cholesterol, low-density cholesterol, and plasma ApoB, compared with controls. However, they found no association between EOAD and high-density lipoprotein or triglycerides.
“Because total cholesterol largely consists of LDL-C, and ApoB is the main lipoprotein of LDL-C, these findings are consistent with one another.
“From these data, we estimated that LDL-C explains 7.6% of the variance in liability to EOAD, independently of APOE e4 ... These results demonstrate that elevated levels of LDL-C [and ApoB] were significantly associated with increased EOAD risk, and this effect was only partially mediated by APOE e4 genotype.”
The results also raised a question: What was driving the association between LDL and EOAD? Because variants of the ApoB gene can either raise or lower LDL, the team examined variants associated with coding changes. These variants were significantly more common in EOAD cases than in controls (5.0% vs. 1.7%).
“Two affected individuals ... were compound heterozygotes, with the remainder being heterozygotes,” the researchers wrote. “Each compound heterozygote case was heterozygous for two different rare coding sites ... Of these four variants, only [one] has been previously described.”
“Our finding of a significant association between rare coding variants in APOB and EOAD independently of APOE is novel, important, and consistent with multiple genome-wide association studies that revealed strong associations between late-onset AD and common intron markers of genes involved in brain cholesterol metabolism [ABCA7, BIN1, CLU, and SORL1]. Furthermore, mice overexpressing ApoB show hyperlipidemia, neurodegeneration, increases in APP, accumulation of amyloid plaques, and cognitive impairment similar to mice overexpressing wild-type human APP. Collectively, these studies and our findings suggest an important role of cholesterol metabolism in AD pathogenesis.”
This research was supported by grants from the Veterans Health Administration, the National Institutes of Health, the To Remember Foundation, the Douglas French Alzheimer’s Foundation, and a contract with the State of California Department of Health Services. Several authors reported financial ties to pharmaceutical companies outside of this work.
SOURCE: Wingo TS et al. JAMA Neurol. 2019 May 28. doi: 10.1001/jamaneurol.2019.0648.
FROM JAMA NEUROLOGY
FIGO outlines global standards for preeclampsia screening
as a one-step procedure, according to new recommendations from The International Federation of Gynecology and Obstetrics (FIGO).
FIGO “encourages all countries and its member associations to adopt and promote strategies to ensure [universal screening],” Liona C. Poon, MD, of Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, and colleagues wrote in a guide published in the International Journal of Gynecology & Obstetrics.
“The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI),” the authors said, noting that the baseline screening test plus a combination of maternal risk factors with MAP is an alternative when PLGF and/or UTPI can’t be measured.
The FIGO recommendations are the culmination of an initiative on PE, which involved a group of international experts convened to discuss and evaluate current knowledge on PE and to “develop a document to frame the issues and suggest key actions to address the health burden posed by PE.” Among the group’s objectives are raising awareness of the links between PE and poor outcomes, and demanding a “clearly defined global health agenda” to address the issue because preeclampsia affects 2%-5% of all pregnant women and is a leading cause of maternal and perinatal morbidity and mortality.
The recommendations represent a consensus document that provides guidance for the first trimester screening and prevention of preterm PE.
“Based on high‐quality evidence, the document outlines current global standards for the first‐trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of preeclampsia in singleton pregnancy,” the authors said, explaining that “[it] provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings” (Int J Gynecol Obstet. 2019;145[Suppl. 1]:1-33).
Specific suggestions are made based on region and resources, and research priorities are outlined to “bridge the current knowledge and evidence gap.”
In addition to universal first trimester screening for PE, the guide stresses a need for improved public health focus, and contingent screening approaches in areas with limited resources (including routine screening for preterm PE by maternal factors and MAP in most cases, with PLGF and UTPI measurement reserved for higher-risk women). It also recommends that women at high risk should receive prophylactic measures such as aspirin therapy beginning at 11–14+6 weeks of gestation at a dose of about 150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed.
Mary E. D’Alton, MD, a maternal-fetal medicine specialist who is chair of the department of obstetrics and gynecology and the Willard C. Rappleye Professor of Obstetrics & Gynecology at Columbia University, New York, was asked to comment on Dr. Sibai’s concerns about the guidelines. “I would simply say that ACOG and SMFM are the organizations in the United States [that] provide educational guidelines about practice in the United States.” Dr. D’Alton assisted Dr. Poon and her associates on the guidelines as an expert on preeclampsia.
Dr. Poon, given a chance to comment on the concern that the FIGO guidelines diverged from those of ACOG and SMFM, responded in an interview, “FIGO, being the global voice for women’s health, likes to ensure that our recommendations are resource appropriate. The objective of these guidelines is to provide a best practice approach, and also offers other pragmatic options for lower resource settings to ensure that preeclampsia testing can be implemented globally. We urge the broader membership of FIGO to adapt these guidelines to their local contexts.”*
She also emphasized that “PerkinElmer’s sponsorship was an unrestricted grant. The company had no involvement in writing the guideline.”*
This work was funded by an unrestricted grant from PerkinElmer, which markets an assay used for first trimester preeclampsia screening. Dr. Poon and her associates reported having no conflicts of interest.
sworcester@mdedge.com
*This article was updated 5/31/2019.
The recommendations regarding screening and management of first trimester preeclampsia as issued by FIGO are largely inconsistent with those from the American College of Obstetricians and Gynecologists (ACOG) and from the Society for Maternal-Fetal Medicine (SMFM), according to Baha M. Sibai, MD.
The FIGO recommendation for first trimester screening and use of low-dose aspirin at 150 mg daily starting at 13 weeks also contradicts the ACOG and SMFM recommendations, he said, noting that a 2019 ACOG practice bulletin on preeclampsia recommends 81 mg of aspirin daily initiated between 12 and 28 weeks of gestation (optimally before 16 weeks of gestation) and continuing until delivery; this is for women with any of the high risk factors for preeclampsia and for women with more than one of the moderate risk factors. Under that recommendation, more women would be eligible based on clinical risk factors. The FIGO approach is not cost effective and will miss many cases of preeclampsia, compared with the ACOG recommendations, he said.
It also should be noted that the FIGO document is funded by a grant from PerkinElmer, which markets a test for PE, he said, stressing that there are “no data suggesting that this test is valid in U.S. pregnancies.”
Dr. Sibai is a maternal-fetal medicine specialist with UT Physicians Maternal-Fetal Medicine Center–Texas Medical Center, and a professor in the department of obstetrics, gynecology, and reproductive sciences at the University of Texas Health Science Center, Houston. He was asked to comment on the article by Poon et al. He said he had no relevant financial disclosures.
The recommendations regarding screening and management of first trimester preeclampsia as issued by FIGO are largely inconsistent with those from the American College of Obstetricians and Gynecologists (ACOG) and from the Society for Maternal-Fetal Medicine (SMFM), according to Baha M. Sibai, MD.
The FIGO recommendation for first trimester screening and use of low-dose aspirin at 150 mg daily starting at 13 weeks also contradicts the ACOG and SMFM recommendations, he said, noting that a 2019 ACOG practice bulletin on preeclampsia recommends 81 mg of aspirin daily initiated between 12 and 28 weeks of gestation (optimally before 16 weeks of gestation) and continuing until delivery; this is for women with any of the high risk factors for preeclampsia and for women with more than one of the moderate risk factors. Under that recommendation, more women would be eligible based on clinical risk factors. The FIGO approach is not cost effective and will miss many cases of preeclampsia, compared with the ACOG recommendations, he said.
It also should be noted that the FIGO document is funded by a grant from PerkinElmer, which markets a test for PE, he said, stressing that there are “no data suggesting that this test is valid in U.S. pregnancies.”
Dr. Sibai is a maternal-fetal medicine specialist with UT Physicians Maternal-Fetal Medicine Center–Texas Medical Center, and a professor in the department of obstetrics, gynecology, and reproductive sciences at the University of Texas Health Science Center, Houston. He was asked to comment on the article by Poon et al. He said he had no relevant financial disclosures.
The recommendations regarding screening and management of first trimester preeclampsia as issued by FIGO are largely inconsistent with those from the American College of Obstetricians and Gynecologists (ACOG) and from the Society for Maternal-Fetal Medicine (SMFM), according to Baha M. Sibai, MD.
The FIGO recommendation for first trimester screening and use of low-dose aspirin at 150 mg daily starting at 13 weeks also contradicts the ACOG and SMFM recommendations, he said, noting that a 2019 ACOG practice bulletin on preeclampsia recommends 81 mg of aspirin daily initiated between 12 and 28 weeks of gestation (optimally before 16 weeks of gestation) and continuing until delivery; this is for women with any of the high risk factors for preeclampsia and for women with more than one of the moderate risk factors. Under that recommendation, more women would be eligible based on clinical risk factors. The FIGO approach is not cost effective and will miss many cases of preeclampsia, compared with the ACOG recommendations, he said.
It also should be noted that the FIGO document is funded by a grant from PerkinElmer, which markets a test for PE, he said, stressing that there are “no data suggesting that this test is valid in U.S. pregnancies.”
Dr. Sibai is a maternal-fetal medicine specialist with UT Physicians Maternal-Fetal Medicine Center–Texas Medical Center, and a professor in the department of obstetrics, gynecology, and reproductive sciences at the University of Texas Health Science Center, Houston. He was asked to comment on the article by Poon et al. He said he had no relevant financial disclosures.
as a one-step procedure, according to new recommendations from The International Federation of Gynecology and Obstetrics (FIGO).
FIGO “encourages all countries and its member associations to adopt and promote strategies to ensure [universal screening],” Liona C. Poon, MD, of Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, and colleagues wrote in a guide published in the International Journal of Gynecology & Obstetrics.
“The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI),” the authors said, noting that the baseline screening test plus a combination of maternal risk factors with MAP is an alternative when PLGF and/or UTPI can’t be measured.
The FIGO recommendations are the culmination of an initiative on PE, which involved a group of international experts convened to discuss and evaluate current knowledge on PE and to “develop a document to frame the issues and suggest key actions to address the health burden posed by PE.” Among the group’s objectives are raising awareness of the links between PE and poor outcomes, and demanding a “clearly defined global health agenda” to address the issue because preeclampsia affects 2%-5% of all pregnant women and is a leading cause of maternal and perinatal morbidity and mortality.
The recommendations represent a consensus document that provides guidance for the first trimester screening and prevention of preterm PE.
“Based on high‐quality evidence, the document outlines current global standards for the first‐trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of preeclampsia in singleton pregnancy,” the authors said, explaining that “[it] provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings” (Int J Gynecol Obstet. 2019;145[Suppl. 1]:1-33).
Specific suggestions are made based on region and resources, and research priorities are outlined to “bridge the current knowledge and evidence gap.”
In addition to universal first trimester screening for PE, the guide stresses a need for improved public health focus, and contingent screening approaches in areas with limited resources (including routine screening for preterm PE by maternal factors and MAP in most cases, with PLGF and UTPI measurement reserved for higher-risk women). It also recommends that women at high risk should receive prophylactic measures such as aspirin therapy beginning at 11–14+6 weeks of gestation at a dose of about 150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed.
Mary E. D’Alton, MD, a maternal-fetal medicine specialist who is chair of the department of obstetrics and gynecology and the Willard C. Rappleye Professor of Obstetrics & Gynecology at Columbia University, New York, was asked to comment on Dr. Sibai’s concerns about the guidelines. “I would simply say that ACOG and SMFM are the organizations in the United States [that] provide educational guidelines about practice in the United States.” Dr. D’Alton assisted Dr. Poon and her associates on the guidelines as an expert on preeclampsia.
Dr. Poon, given a chance to comment on the concern that the FIGO guidelines diverged from those of ACOG and SMFM, responded in an interview, “FIGO, being the global voice for women’s health, likes to ensure that our recommendations are resource appropriate. The objective of these guidelines is to provide a best practice approach, and also offers other pragmatic options for lower resource settings to ensure that preeclampsia testing can be implemented globally. We urge the broader membership of FIGO to adapt these guidelines to their local contexts.”*
She also emphasized that “PerkinElmer’s sponsorship was an unrestricted grant. The company had no involvement in writing the guideline.”*
This work was funded by an unrestricted grant from PerkinElmer, which markets an assay used for first trimester preeclampsia screening. Dr. Poon and her associates reported having no conflicts of interest.
sworcester@mdedge.com
*This article was updated 5/31/2019.
as a one-step procedure, according to new recommendations from The International Federation of Gynecology and Obstetrics (FIGO).
FIGO “encourages all countries and its member associations to adopt and promote strategies to ensure [universal screening],” Liona C. Poon, MD, of Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, and colleagues wrote in a guide published in the International Journal of Gynecology & Obstetrics.
“The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI),” the authors said, noting that the baseline screening test plus a combination of maternal risk factors with MAP is an alternative when PLGF and/or UTPI can’t be measured.
The FIGO recommendations are the culmination of an initiative on PE, which involved a group of international experts convened to discuss and evaluate current knowledge on PE and to “develop a document to frame the issues and suggest key actions to address the health burden posed by PE.” Among the group’s objectives are raising awareness of the links between PE and poor outcomes, and demanding a “clearly defined global health agenda” to address the issue because preeclampsia affects 2%-5% of all pregnant women and is a leading cause of maternal and perinatal morbidity and mortality.
The recommendations represent a consensus document that provides guidance for the first trimester screening and prevention of preterm PE.
“Based on high‐quality evidence, the document outlines current global standards for the first‐trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of preeclampsia in singleton pregnancy,” the authors said, explaining that “[it] provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings” (Int J Gynecol Obstet. 2019;145[Suppl. 1]:1-33).
Specific suggestions are made based on region and resources, and research priorities are outlined to “bridge the current knowledge and evidence gap.”
In addition to universal first trimester screening for PE, the guide stresses a need for improved public health focus, and contingent screening approaches in areas with limited resources (including routine screening for preterm PE by maternal factors and MAP in most cases, with PLGF and UTPI measurement reserved for higher-risk women). It also recommends that women at high risk should receive prophylactic measures such as aspirin therapy beginning at 11–14+6 weeks of gestation at a dose of about 150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed.
Mary E. D’Alton, MD, a maternal-fetal medicine specialist who is chair of the department of obstetrics and gynecology and the Willard C. Rappleye Professor of Obstetrics & Gynecology at Columbia University, New York, was asked to comment on Dr. Sibai’s concerns about the guidelines. “I would simply say that ACOG and SMFM are the organizations in the United States [that] provide educational guidelines about practice in the United States.” Dr. D’Alton assisted Dr. Poon and her associates on the guidelines as an expert on preeclampsia.
Dr. Poon, given a chance to comment on the concern that the FIGO guidelines diverged from those of ACOG and SMFM, responded in an interview, “FIGO, being the global voice for women’s health, likes to ensure that our recommendations are resource appropriate. The objective of these guidelines is to provide a best practice approach, and also offers other pragmatic options for lower resource settings to ensure that preeclampsia testing can be implemented globally. We urge the broader membership of FIGO to adapt these guidelines to their local contexts.”*
She also emphasized that “PerkinElmer’s sponsorship was an unrestricted grant. The company had no involvement in writing the guideline.”*
This work was funded by an unrestricted grant from PerkinElmer, which markets an assay used for first trimester preeclampsia screening. Dr. Poon and her associates reported having no conflicts of interest.
sworcester@mdedge.com
*This article was updated 5/31/2019.
FROM THE INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
Why aren’t preferred DMTs prescribed for MS? Neurologists point to insurers, patients
SEATTLE –
Specifically, “it appears that patient reluctance to start moderate-efficacy DMTs is a major factor and may be impeding a significant uptake of the oral drugs in treatment-naive patients,” said study lead author Virginia Schobel, MSc, of the consulting firm Spherix Global Insights, who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The third annual survey of neurologists was conducted in December 2018, and 218 neurologists took part. Participants answered questions via an online survey and provided cross-sectional retrospective chart reviews of 1,059 MS patients who started their first DMT over the previous 3 months. The survey participants managed the initial DMT selection in 935 of the cases.
For this survey, Ms. Schobel said, researchers focused on exploring reasons why data aren’t showing a major trend toward oral DMTs as first-line treatment. “A good proportion of neurologists agree that this is their preferred method, but we are not seeing the market move,” she said.
The survey asked neurologists if they agree with this statement: “When initiating a patient on DMT therapy, I prefer to use a DMT aggressive approach, using a high-efficacy agent as opposed to a therapy escalation approach whereby I start with a traditional first-line DMT and only progress to second line if/when the patient does not have an optimal response.” Nearly half (49%) of the neurologists agreed, while 16% disagreed and 36% were neutral.
Neurologists reported initiating their preferred DMT 77% of the time (standard efficacy DMTs), 81% of the time (moderate efficacy), and 75% (high efficacy).
When asked why they weren’t able to prescribe their top recommended DMT, neurologists offered these answers:
** In standard-efficacy cases (n = 96), insurance hitches – formulary limitations or denial – were responsible 67% of the time. Patient refusal or preference for another DMT were responsible 33% of the time, and other reasons accounted for 1%.
Why do patients face insurance hassles for standard-efficacy drugs? Ms. Schobel noted that generics are available for these drugs, and insurers may prefer them.
** In moderate-efficacy cases (n = 63), insurance hitches accounted for 40% of cases, while patient refusal made up 59% with other reasons at 3%.
** In high-efficacy cases (n = 46), insurance hitches accounted for 59% of cases, while patient refusal explained 41% of cases. Of the latter group, reasons included tolerability concerns (42%) and safety concerns other than progressive multifocal leukoencephalopathy (PML) risks (37%)
No study funding is reported, and the study authors report no relevant disclosures.
SEATTLE –
Specifically, “it appears that patient reluctance to start moderate-efficacy DMTs is a major factor and may be impeding a significant uptake of the oral drugs in treatment-naive patients,” said study lead author Virginia Schobel, MSc, of the consulting firm Spherix Global Insights, who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The third annual survey of neurologists was conducted in December 2018, and 218 neurologists took part. Participants answered questions via an online survey and provided cross-sectional retrospective chart reviews of 1,059 MS patients who started their first DMT over the previous 3 months. The survey participants managed the initial DMT selection in 935 of the cases.
For this survey, Ms. Schobel said, researchers focused on exploring reasons why data aren’t showing a major trend toward oral DMTs as first-line treatment. “A good proportion of neurologists agree that this is their preferred method, but we are not seeing the market move,” she said.
The survey asked neurologists if they agree with this statement: “When initiating a patient on DMT therapy, I prefer to use a DMT aggressive approach, using a high-efficacy agent as opposed to a therapy escalation approach whereby I start with a traditional first-line DMT and only progress to second line if/when the patient does not have an optimal response.” Nearly half (49%) of the neurologists agreed, while 16% disagreed and 36% were neutral.
Neurologists reported initiating their preferred DMT 77% of the time (standard efficacy DMTs), 81% of the time (moderate efficacy), and 75% (high efficacy).
When asked why they weren’t able to prescribe their top recommended DMT, neurologists offered these answers:
** In standard-efficacy cases (n = 96), insurance hitches – formulary limitations or denial – were responsible 67% of the time. Patient refusal or preference for another DMT were responsible 33% of the time, and other reasons accounted for 1%.
Why do patients face insurance hassles for standard-efficacy drugs? Ms. Schobel noted that generics are available for these drugs, and insurers may prefer them.
** In moderate-efficacy cases (n = 63), insurance hitches accounted for 40% of cases, while patient refusal made up 59% with other reasons at 3%.
** In high-efficacy cases (n = 46), insurance hitches accounted for 59% of cases, while patient refusal explained 41% of cases. Of the latter group, reasons included tolerability concerns (42%) and safety concerns other than progressive multifocal leukoencephalopathy (PML) risks (37%)
No study funding is reported, and the study authors report no relevant disclosures.
SEATTLE –
Specifically, “it appears that patient reluctance to start moderate-efficacy DMTs is a major factor and may be impeding a significant uptake of the oral drugs in treatment-naive patients,” said study lead author Virginia Schobel, MSc, of the consulting firm Spherix Global Insights, who spoke in an interview prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The third annual survey of neurologists was conducted in December 2018, and 218 neurologists took part. Participants answered questions via an online survey and provided cross-sectional retrospective chart reviews of 1,059 MS patients who started their first DMT over the previous 3 months. The survey participants managed the initial DMT selection in 935 of the cases.
For this survey, Ms. Schobel said, researchers focused on exploring reasons why data aren’t showing a major trend toward oral DMTs as first-line treatment. “A good proportion of neurologists agree that this is their preferred method, but we are not seeing the market move,” she said.
The survey asked neurologists if they agree with this statement: “When initiating a patient on DMT therapy, I prefer to use a DMT aggressive approach, using a high-efficacy agent as opposed to a therapy escalation approach whereby I start with a traditional first-line DMT and only progress to second line if/when the patient does not have an optimal response.” Nearly half (49%) of the neurologists agreed, while 16% disagreed and 36% were neutral.
Neurologists reported initiating their preferred DMT 77% of the time (standard efficacy DMTs), 81% of the time (moderate efficacy), and 75% (high efficacy).
When asked why they weren’t able to prescribe their top recommended DMT, neurologists offered these answers:
** In standard-efficacy cases (n = 96), insurance hitches – formulary limitations or denial – were responsible 67% of the time. Patient refusal or preference for another DMT were responsible 33% of the time, and other reasons accounted for 1%.
Why do patients face insurance hassles for standard-efficacy drugs? Ms. Schobel noted that generics are available for these drugs, and insurers may prefer them.
** In moderate-efficacy cases (n = 63), insurance hitches accounted for 40% of cases, while patient refusal made up 59% with other reasons at 3%.
** In high-efficacy cases (n = 46), insurance hitches accounted for 59% of cases, while patient refusal explained 41% of cases. Of the latter group, reasons included tolerability concerns (42%) and safety concerns other than progressive multifocal leukoencephalopathy (PML) risks (37%)
No study funding is reported, and the study authors report no relevant disclosures.
REPORTING FROM CMSC 2019
Modest evidence for benefit in studies of cannabis in MS
SEATTLE – Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Ms. Breward spoke prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Ms. Breward and colleagues focused on 60 studies - 26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols (Sativex), an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the United States.
According to Ms. Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8) and cognition (n = 6).
The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
As for results, the researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Ms. Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids, she said.
“However,” she added, “the variability in study quality – and in the products and regimens studied – make it hard to draw any conclusions about specific products and doses that may have the most potential benefit.”
As for adverse effects, dried cannabis was linked to decreased long-term cognitive function, which is distinct from being temporarily high, Ms. Breward said.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
No study funding is reported and the authors report no relevant disclosures.
SEATTLE – Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Ms. Breward spoke prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Ms. Breward and colleagues focused on 60 studies - 26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols (Sativex), an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the United States.
According to Ms. Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8) and cognition (n = 6).
The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
As for results, the researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Ms. Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids, she said.
“However,” she added, “the variability in study quality – and in the products and regimens studied – make it hard to draw any conclusions about specific products and doses that may have the most potential benefit.”
As for adverse effects, dried cannabis was linked to decreased long-term cognitive function, which is distinct from being temporarily high, Ms. Breward said.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
No study funding is reported and the authors report no relevant disclosures.
SEATTLE – Reviewers found modest evidence of benefit and plenty of room for more research.
“Cannabis-based medicine may be useful for refractory MS symptoms, especially spasticity and pain, and side effects are usually well tolerated,” study lead author Natasha Breward, a graduate student at the College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, said in an interview. Ms. Breward spoke prior to the presentation of the study findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
For the review, Ms. Breward and colleagues focused on 60 studies - 26 randomized controlled trials and 34 trials with other designs. Forty of the studies used nabiximols (Sativex), an oromucosal spray that is derived from the cannabis sativa plant and approved for use in multiple countries but not yet in the United States.
According to Ms. Breward, some of the other treatments included dried cannabis that is smoked or eaten and cannabidiol that’s typically delivered with tetrahydrocannabinol (THC) either oromucosally or as an oral capsule.
MS symptoms treated in the studies included spasticity (n = 29), pain (n = 8) and cognition (n = 6).
The researchers considered 22 studies to be poor quality, 14 to be fair quality, and 24 to be good/excellent quality.
As for results, the researchers found that the cannabis-based medicine “significantly reduced spasticity and pain in several individual good-quality studies,” Ms. Breward said. The drugs seem to work by inhibiting neurotransmitter release via cannabinoids, she said.
“However,” she added, “the variability in study quality – and in the products and regimens studied – make it hard to draw any conclusions about specific products and doses that may have the most potential benefit.”
As for adverse effects, dried cannabis was linked to decreased long-term cognitive function, which is distinct from being temporarily high, Ms. Breward said.
“Further research should focus on the use of different products and formulations of cannabis-based medicine such as cannabis oil and cannabidiol-prominent products, as no studies have focused on this area,” she said. “Research should also look at the potential of cannabis-based medicine for the treatment of disease progression, as cannabinoids are anti-inflammatory and immunomodulatory. Finally, more research regarding the potentially synergistic effects of cannabis-based medicine administered with current MS medications would also be useful.”
No study funding is reported and the authors report no relevant disclosures.
REPORTING FROM CMSC 2019
Refrigerator-stable varicella vaccine held safe and effective
profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.
In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.
The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.
The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.
Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.
Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.
SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.
profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.
In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.
The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.
The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.
Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.
Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.
SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.
profiles when administered concomitantly with MMR vaccine, according to a study in Vaccine.
In this double-blind, controlled, multicenter study, Keith S. Reisinger of Primary Physicians Research, Pittsburgh, and his colleagues randomized 958 subjects aged 12-23 months to receive either 8,000 plaque-forming units (PFU) refrigerated vaccine (n = 320; group 1), 25,000 PFU refrigerated vaccine (n = 315; group 2), or 10,000 PFU frozen vaccine (n = 323; group 3), and subjects in all three groups also received MMR vaccine. The primary endpoint for immunogenicity was percentage of subjects with at least 5 titers of varicella antibody according to glycoprotein enzyme-linked immunosorbent assay among the three groups 6 weeks post vaccination; the primary safety endpoint was incidences of vaccine-related adverse events during days 0-42 post vaccination.
The percentages of subjects meeting the primary endpoint for immunogenicity were comparable among the groups, at 93%, 94%, and 95% for groups 1, 2, and 3, respectively. Results for the safety endpoints also were similar among the groups; for example, rates of injection-site adverse events or vaccine-related injection-site adverse events were 44%, 40%, and 43%, with no statistically significant between-group differences.
The study authors noted that one of the problems with having only frozen formulations is how that limits availability in parts of the world where only refrigeration of 2°C–8°C is available. “Use of a refrigerator-stable formulation of varicella vaccine will allow for increased availability of the product throughout the world and may help to increase vaccination rates against varicella,” they concluded.
Strengths of the study included its head-to-head design. Limitations included how adverse events were based on parental reporting.
Some authors reported relationships, including employment, with Merck & Co, which developed the vaccine in this study and funded the study.
SOURCE: Reisinger KS et al. Vaccine. 2018 Aug 23. doi: 10.1016/j.vaccine.2018.01.089.
Pregnancy-Related Deaths: A “Web of Missed Opportunities”
The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common. But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.
The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.
The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.
The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:
- Help patients manage their chronic conditions;
- Teach patients about warning signs; and
- Use tools to flag warning signs early so women can receive timely treatment
Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.
The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common. But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.
The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.
The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.
The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:
- Help patients manage their chronic conditions;
- Teach patients about warning signs; and
- Use tools to flag warning signs early so women can receive timely treatment
Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.
The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common. But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.
The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.
The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.
The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:
- Help patients manage their chronic conditions;
- Teach patients about warning signs; and
- Use tools to flag warning signs early so women can receive timely treatment
Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.
Generalized rash following ankle ulceration
At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.
A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.
This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.
Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.
Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.
Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.
In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.
This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.
At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.
A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.
This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.
Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.
Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.
Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.
In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.
This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.
At the hospital, the physicians noted that there were no lesions on the mucous membranes of the patient’s eyes, ears, nose, mouth or anus and his vital signs were within normal limits. He was empirically treated with 1 dose of methylprednisolone (125 mg intravenous [IV]) and started on IV piperacillin-tazobactam and vancomycin. The patient subsequently revealed that he’d had a similar experience a year earlier after being treated with TMP-SMX for cellulitis. During the previous episode, he said the lesions were located on the exact same areas of his glans penis and chin. Based on the morphologic characteristics of the eruption and the history of similar lesions that appeared following previous treatment with TMP-SMX, the physician diagnosed disseminated fixed-drug eruption in this patient.
A fixed-drug eruption is an adverse cutaneous reaction to a drug that is defined by a dusky red or violaceous macule, which evolves into a patch, and eventually, an edematous plaque. Fixed-drug eruptions are typically solitary, but may be generalized (as was the case with this patient). The pathophysiology of the disease involves resident intra-epidermal CD8+ T-cells resembling effector memory T-cells. These T-cells are increased in number at the dermoepidermal junction of normal appearing skin; their aberrant activation leads to an inflammatory response, stimulating tissue destruction and formation of the classic fixed-drug lesion.
This diagnosis usually is made based on a history of similar lesions recurring at the same location in response to a specific drug and the classic physical exam findings of well-demarcated, edematous, and violaceous plaques. A skin biopsy may be performed to confirm a fixed-drug eruption in the case of clinical equipoise.
Fixed-drug eruptions occasionally exhibit bullae and erosions and must be differentiated from more serious generalized bullous diseases, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The differential diagnosis also includes erythema multiforme, early bullous drug eruption, and bullous arthropod assault, which may leave similar hyperpigmented patches.
Management of a disseminated fixed-drug eruption requires a thorough history to identify the causative agent (including over-the-counter drugs, herbals, topicals, and eye drops). Most patients are asymptomatic, but some (like this patient) are symptomatic and experience generalized pruritus, cutaneous burning, and/or pain. Symptomatic therapy includes oral antihistamines and potent topical glucocorticoid ointment for non-eroded lesions. Additionally, if not medically contraindicated, oral steroids may be used for generalized or extremely painful mucosal lesions at a dose of 0.5 mg/kg daily for 3 to 5 days.
Local wound care of eroded lesions includes keeping the site moist with a bland emollient and bandaging. The inciting agent must be added to the patient’s allergy list and avoided in the future. In equivocal cases, it is prudent to admit the patient for observation to ensure that the eruption is not a nascent SJS or TEN eruption.
In this case, the patient was admitted to the observation unit overnight to monitor for the appearance of systemic symptoms and to assess the evolution of the rash for further mucosal involvement that could have indicated SJS. Upon reassessment the next day, his older lesions had evolved into vesiculated and necrotic areas as per the natural history of severe fixed-drug eruption. He was prescribed prednisone 40 mg/d for 3 days to help with local inflammation, pain, and itching. TMP-SMX was added to his allergy list and he was given local wound care instructions. He was told to return if he developed any systemic symptoms.
This case was adapted from: Bucher J, Rahnama-Moghadam S, Osswald S. Generalized rash follows ankle ulceration. J Fam Pract. 2016;65:489-491.
Children’s book effectively assesses literary skills during well-child visits
reported John S. Hutton, MS, MD, of Cincinnati Children’s Hospital Medical Center, and his associates.
The Reading House (TRH) is a 14-page, full-color, board book with a simple, rhyming narrative and illustrated content showing children of various ethnicities and sexes going about their day. For the study, published in Pediatrics, 278 children aged 36-52 months (mean age, 43.1 months) were recruited from seven pediatric primary care clinics, two of which were affiliated with an academic children’s hospital primarily serving families of lower socioeconomic status. The children’s reading comprehension was measured by way of a 9-item TRH assessment, as well as the 25-item Get Ready to Read! (GRTR) validated measure; parent, child, and provider impressions of TRH also were collected.
The mean TRH assessment score was 4.2, and the mean GRTR score was 11.1. The TRH score was positively associated with GRTR score, female sex, private practice, and child age (Pediatrics 2019 May 30. doi: 10.1542/peds.2018-3843).
Of the 72 clinical providers surveyed on the effectiveness of the TRH assessment, most reported that the assessment was not invasive in patient flow (93% not at all, 6% somewhat, 1% very much), that TRH would be feasible to administer (49% yes, 43% not sure, 8% no), would be clinically useful (67% yes, 31% not sure, 2% no), and would be useful for families (85% yes, 14% not sure, 1% no). Similar results on the effectiveness and enjoyability of TRH were reported by parents and children.
“Although psychometric properties are critical, effective screening should be perceived as useful and not burdensome or invasive. Responses to parent, child, and provider surveys were favorable, which suggests that TRH screening may be an enjoyable and valuable addition to well-child visits,” the investigators wrote.
Dr. Hutton conceived, wrote, and edited the children’s book used in the study, and is the founder of the company that published the book, although he receives no salary or compensation for this role. The book’s intended use is as a screening tool, distributed at low cost to clinical practices and organizations. The other study authors did not report any conflicts of interest.
reported John S. Hutton, MS, MD, of Cincinnati Children’s Hospital Medical Center, and his associates.
The Reading House (TRH) is a 14-page, full-color, board book with a simple, rhyming narrative and illustrated content showing children of various ethnicities and sexes going about their day. For the study, published in Pediatrics, 278 children aged 36-52 months (mean age, 43.1 months) were recruited from seven pediatric primary care clinics, two of which were affiliated with an academic children’s hospital primarily serving families of lower socioeconomic status. The children’s reading comprehension was measured by way of a 9-item TRH assessment, as well as the 25-item Get Ready to Read! (GRTR) validated measure; parent, child, and provider impressions of TRH also were collected.
The mean TRH assessment score was 4.2, and the mean GRTR score was 11.1. The TRH score was positively associated with GRTR score, female sex, private practice, and child age (Pediatrics 2019 May 30. doi: 10.1542/peds.2018-3843).
Of the 72 clinical providers surveyed on the effectiveness of the TRH assessment, most reported that the assessment was not invasive in patient flow (93% not at all, 6% somewhat, 1% very much), that TRH would be feasible to administer (49% yes, 43% not sure, 8% no), would be clinically useful (67% yes, 31% not sure, 2% no), and would be useful for families (85% yes, 14% not sure, 1% no). Similar results on the effectiveness and enjoyability of TRH were reported by parents and children.
“Although psychometric properties are critical, effective screening should be perceived as useful and not burdensome or invasive. Responses to parent, child, and provider surveys were favorable, which suggests that TRH screening may be an enjoyable and valuable addition to well-child visits,” the investigators wrote.
Dr. Hutton conceived, wrote, and edited the children’s book used in the study, and is the founder of the company that published the book, although he receives no salary or compensation for this role. The book’s intended use is as a screening tool, distributed at low cost to clinical practices and organizations. The other study authors did not report any conflicts of interest.
reported John S. Hutton, MS, MD, of Cincinnati Children’s Hospital Medical Center, and his associates.
The Reading House (TRH) is a 14-page, full-color, board book with a simple, rhyming narrative and illustrated content showing children of various ethnicities and sexes going about their day. For the study, published in Pediatrics, 278 children aged 36-52 months (mean age, 43.1 months) were recruited from seven pediatric primary care clinics, two of which were affiliated with an academic children’s hospital primarily serving families of lower socioeconomic status. The children’s reading comprehension was measured by way of a 9-item TRH assessment, as well as the 25-item Get Ready to Read! (GRTR) validated measure; parent, child, and provider impressions of TRH also were collected.
The mean TRH assessment score was 4.2, and the mean GRTR score was 11.1. The TRH score was positively associated with GRTR score, female sex, private practice, and child age (Pediatrics 2019 May 30. doi: 10.1542/peds.2018-3843).
Of the 72 clinical providers surveyed on the effectiveness of the TRH assessment, most reported that the assessment was not invasive in patient flow (93% not at all, 6% somewhat, 1% very much), that TRH would be feasible to administer (49% yes, 43% not sure, 8% no), would be clinically useful (67% yes, 31% not sure, 2% no), and would be useful for families (85% yes, 14% not sure, 1% no). Similar results on the effectiveness and enjoyability of TRH were reported by parents and children.
“Although psychometric properties are critical, effective screening should be perceived as useful and not burdensome or invasive. Responses to parent, child, and provider surveys were favorable, which suggests that TRH screening may be an enjoyable and valuable addition to well-child visits,” the investigators wrote.
Dr. Hutton conceived, wrote, and edited the children’s book used in the study, and is the founder of the company that published the book, although he receives no salary or compensation for this role. The book’s intended use is as a screening tool, distributed at low cost to clinical practices and organizations. The other study authors did not report any conflicts of interest.
FROM PEDIATRICS
AAD’s augmented intelligence position statement provides look to the future
A blueprint for the future of into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.
The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”
“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”
“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.
“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”
The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”
While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”
The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”
The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.
A blueprint for the future of into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.
The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”
“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”
“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.
“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”
The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”
While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”
The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”
The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.
A blueprint for the future of into clinical settings, and postmarketing surveillance – is the focus of a newly published American Academy of Dermatology (AAD) position statement.
The statement describes AuI as “a concept that focuses on artificial intelligence’s (AI) assistive role,” emphasizing that AuI is “designed to enhance human intelligence and the physician/patient relationship,” not to replace that relationship. The statement, available on the AAD website, also emphasizes the importance of the human-centered nature of this concept as dermatologists integrate AuI into their practice, noting that “patients should feel well cared for even when interacting with software.”
“We are at the precipice of seeing the beginnings of augmented intelligence tools influence our practice,” statement coauthor Justin M. Ko, MD, MBA, said in an interview. “At the outset, it will likely be systems and tools that are working on practice management processes, insights, and analytics. However, I don’t believe we’re far from seeing the mainstream integration say, of triage, point of care diagnostic support, or chronic disease management capabilities that rely in some part on augmented intelligence models.”
“The key is that we recognize that this is on the horizon, and that we actively work to shape the development and deployment of these tools in a responsible way that enhances patient care and ensures that patient safety is held paramount,” added Dr. Ko, director and chief of medical dermatology at Stanford (Calif.) University.
“We want patients and clinicians to recognize the potential of such tools to augment the core care relationship and improve the delivery of such care,” he explained. “At the same time, we know that, from the technology that exists all around us in all aspects of our lives, that despite the best intentions, there [may be] unintended consequences in the medical realm. We must be cognizant of possibilities, for example, of amplifying bias and increasing health inequity, and take an active approach to mitigating these risks.”
The AAD position statement notes that high-quality AuI will be “designed and evaluated in a manner that enables the delivery of high-quality care to patients.” During development and clinical deployment, the statement highlighted the importance of collaboration with practitioners, and that “AuI must integrate into physician and provider workflows.” The statement advises that AuI tools should be regulated appropriately, and that postmarketing surveillance will be necessary after clinical launch of these tools, measuring outcomes such as “quality, cost, and/or efficiency of care delivery.”
While the first half of the statement provides a roadmap for AuI development and implementation, the second half further emphasizes collaboration and communication with a number of stakeholders. “Effective and ethical development and implementation of AuI will require continuous engagement, education, exploration of privacy and medical-legal issues, and advocacy,” the statement says. “Although the promise of AuI to improve health and wellness holds significant potential,” the statement says, “issues related to privacy and medical-legal complications are amplified by technology that requires transmission of data beyond the confines of a providers’ institution. Protected Health Information must be managed with effective safeguards to prevent inadvertent exposure.”
The conclusion of the statement revisits the game-changing nature of AuI while asserting the AAD’s commitment to guiding integration with dermatology practice. “AuI has the potential to transform our collective and personal experience of health, health care, and wellness,” the AAD wrote. “To achieve this potential, deliberate and diligent efforts must be taken to engage and collaborate with stakeholders and policy makers. The Academy hopes to work with administrative and legislative colleagues to create policies that promote AuI that is high quality, inclusive, equitable, and accessible. Through collaboration and research, the Academy strives to guide the design, implementation, and regulation of these technologies and augment care for all.”
The statement also includes a glossary of terms used in this area. The AAD’s Ad Hoc Taskforce on Augmented Intelligence wrote the position statement; Dr. Ko is on the task force and serves as its chairman.
New tickborne virus emerges in China
A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.
The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.
The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.
Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.
The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.
Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.
ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.
Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.
Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.
The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.
New technology and genomic surveys will continue to help identify emerging pathogens, however, “they may provide limited value in understanding the mechanisms of disease emergence,” wrote Nikos Vasilakis, PhD, and David H. Walker, MD, in an accompanying editorial. An active surveillance program allowed the investigators of the previously unknown tickborne pathogen in China to identify a group of patients with similar history. The new pathogen was classified as one of the jingmenviruses, which “reveal that RNA virus segmentation is an evolutionary process that has occurred in previously unanticipated circumstances.” This study by Wang et al. shows that these viruses are not limited to arthropod hosts but can be dangerous to humans.
The new pathogen had likely been evolving for some time before it was discovered, the editorialists said. “The key to making such discoveries is the study of ill persons, isolation of the etiologic agent, use of tools that will reveal the nature of the agent (e.g., electron microscopy), and application of the appropriate tools for definitive characterization (e.g., sequencing of the RNA genome),” they emphasized. However, to mitigate outbreaks, “proactive, real-time surveillance” may be more cost effective than extensive genomic surveys, they noted (N Engl J Med. 2019 May 29. doi: 10.1056/NEJMe1901212).
Dr. Vasilakis and Dr. Walker are affiliated with the department of pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston. They had no financial conflicts to disclose.
New technology and genomic surveys will continue to help identify emerging pathogens, however, “they may provide limited value in understanding the mechanisms of disease emergence,” wrote Nikos Vasilakis, PhD, and David H. Walker, MD, in an accompanying editorial. An active surveillance program allowed the investigators of the previously unknown tickborne pathogen in China to identify a group of patients with similar history. The new pathogen was classified as one of the jingmenviruses, which “reveal that RNA virus segmentation is an evolutionary process that has occurred in previously unanticipated circumstances.” This study by Wang et al. shows that these viruses are not limited to arthropod hosts but can be dangerous to humans.
The new pathogen had likely been evolving for some time before it was discovered, the editorialists said. “The key to making such discoveries is the study of ill persons, isolation of the etiologic agent, use of tools that will reveal the nature of the agent (e.g., electron microscopy), and application of the appropriate tools for definitive characterization (e.g., sequencing of the RNA genome),” they emphasized. However, to mitigate outbreaks, “proactive, real-time surveillance” may be more cost effective than extensive genomic surveys, they noted (N Engl J Med. 2019 May 29. doi: 10.1056/NEJMe1901212).
Dr. Vasilakis and Dr. Walker are affiliated with the department of pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston. They had no financial conflicts to disclose.
New technology and genomic surveys will continue to help identify emerging pathogens, however, “they may provide limited value in understanding the mechanisms of disease emergence,” wrote Nikos Vasilakis, PhD, and David H. Walker, MD, in an accompanying editorial. An active surveillance program allowed the investigators of the previously unknown tickborne pathogen in China to identify a group of patients with similar history. The new pathogen was classified as one of the jingmenviruses, which “reveal that RNA virus segmentation is an evolutionary process that has occurred in previously unanticipated circumstances.” This study by Wang et al. shows that these viruses are not limited to arthropod hosts but can be dangerous to humans.
The new pathogen had likely been evolving for some time before it was discovered, the editorialists said. “The key to making such discoveries is the study of ill persons, isolation of the etiologic agent, use of tools that will reveal the nature of the agent (e.g., electron microscopy), and application of the appropriate tools for definitive characterization (e.g., sequencing of the RNA genome),” they emphasized. However, to mitigate outbreaks, “proactive, real-time surveillance” may be more cost effective than extensive genomic surveys, they noted (N Engl J Med. 2019 May 29. doi: 10.1056/NEJMe1901212).
Dr. Vasilakis and Dr. Walker are affiliated with the department of pathology, Center for Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston. They had no financial conflicts to disclose.
A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.
The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.
The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.
Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.
The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.
Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.
ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.
Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.
Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.
The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.
A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.
The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.
The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.
Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.
The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.
Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.
ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.
Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.
Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.
The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE