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Sugary Drink Intake May be Associated with MS Severity
Key clinical point: Among patients with multiple sclerosis, consumption of sugar-sweetened beverages may be associated with more severe disability.
Major finding: Patients in the top quartile of sugar-sweetened beverage intake had an average EDSS of 4.1 and patients in the bottom quartile had an average EDSS of 3.4.
Study details: Cross-sectional study of 135 patients with MS.
Disclosures: Dr. Meier-Gerdingh had no disclosures. Coauthors reported research support and personal compensation from pharmaceutical companies.
Citation: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
Key clinical point: Among patients with multiple sclerosis, consumption of sugar-sweetened beverages may be associated with more severe disability.
Major finding: Patients in the top quartile of sugar-sweetened beverage intake had an average EDSS of 4.1 and patients in the bottom quartile had an average EDSS of 3.4.
Study details: Cross-sectional study of 135 patients with MS.
Disclosures: Dr. Meier-Gerdingh had no disclosures. Coauthors reported research support and personal compensation from pharmaceutical companies.
Citation: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
Key clinical point: Among patients with multiple sclerosis, consumption of sugar-sweetened beverages may be associated with more severe disability.
Major finding: Patients in the top quartile of sugar-sweetened beverage intake had an average EDSS of 4.1 and patients in the bottom quartile had an average EDSS of 3.4.
Study details: Cross-sectional study of 135 patients with MS.
Disclosures: Dr. Meier-Gerdingh had no disclosures. Coauthors reported research support and personal compensation from pharmaceutical companies.
Citation: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
Researchers Examine Vitamin D, Skin Pigmentation, and Outcomes of Pediatric MS
Key clinical point: The relationship between vitamin D status and MS outcome in children relates to skin pigmentation.
Major finding: About 46% of children with MS were HLA-DRB1*15 positive.
Study details: A multisite, prospective study of 259 children with MS.
Disclosures: Ms. Dunn had no disclosures, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
Citation: Dunn C et al. AAN 2019, Abstract S19.007.
Key clinical point: The relationship between vitamin D status and MS outcome in children relates to skin pigmentation.
Major finding: About 46% of children with MS were HLA-DRB1*15 positive.
Study details: A multisite, prospective study of 259 children with MS.
Disclosures: Ms. Dunn had no disclosures, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
Citation: Dunn C et al. AAN 2019, Abstract S19.007.
Key clinical point: The relationship between vitamin D status and MS outcome in children relates to skin pigmentation.
Major finding: About 46% of children with MS were HLA-DRB1*15 positive.
Study details: A multisite, prospective study of 259 children with MS.
Disclosures: Ms. Dunn had no disclosures, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
Citation: Dunn C et al. AAN 2019, Abstract S19.007.
FDA grants Priority Review to Vascepa for cardiovascular risk reduction
The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).
If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.
The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.
The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.
Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.
“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.
The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.
The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).
If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.
The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.
The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.
Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.
“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.
The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.
The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).
If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.
The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.
The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.
Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.
“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.
The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.
FDA approves first drug for steroid-refractory acute GVHD
The Food and Drug Administration has approved Jafaki (ruxolitinib) for treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.
Ruxolitinib will be made available to appropriate patients immediately, according to a statement from Incyte, which markets the drug. The company noted that ruxolitinib is the first FDA-approved treatment for this indication.
The approval is based on data from the open-label, single-arm, multicenter REACH1 trial, which studied ruxolitinib in combination with corticosteroids. The 71 patients in the trial had grade 2-4 acute GVHD after allogeneic hematopoietic stem cell transplant; of these patients, 49 were refractory to steroids alone, 12 had received at least two prior therapies for GVHD, and 10 did not otherwise meet the FDA definition of steroid refractory.
The trial’s primary endpoints were day-28 overall response rate and response duration. Among the 49 patients with steroid only–refractory GVHD, the overall response rate was 100% for grade 2 GVHD, 40.7% for grade 3, and 44.4% for grade 4. Median response duration was 16 days. For all 49 of these patients, the overall response rate was 57%, and the complete response rate was 31%.
Among all 71 participants, the most frequently reported adverse reactions were infections (55%) and edema (51%); anemia (71%), thrombocytopenia (75%), and neutropenia (58%) were the most common laboratory abnormalities.
The Food and Drug Administration has approved Jafaki (ruxolitinib) for treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.
Ruxolitinib will be made available to appropriate patients immediately, according to a statement from Incyte, which markets the drug. The company noted that ruxolitinib is the first FDA-approved treatment for this indication.
The approval is based on data from the open-label, single-arm, multicenter REACH1 trial, which studied ruxolitinib in combination with corticosteroids. The 71 patients in the trial had grade 2-4 acute GVHD after allogeneic hematopoietic stem cell transplant; of these patients, 49 were refractory to steroids alone, 12 had received at least two prior therapies for GVHD, and 10 did not otherwise meet the FDA definition of steroid refractory.
The trial’s primary endpoints were day-28 overall response rate and response duration. Among the 49 patients with steroid only–refractory GVHD, the overall response rate was 100% for grade 2 GVHD, 40.7% for grade 3, and 44.4% for grade 4. Median response duration was 16 days. For all 49 of these patients, the overall response rate was 57%, and the complete response rate was 31%.
Among all 71 participants, the most frequently reported adverse reactions were infections (55%) and edema (51%); anemia (71%), thrombocytopenia (75%), and neutropenia (58%) were the most common laboratory abnormalities.
The Food and Drug Administration has approved Jafaki (ruxolitinib) for treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.
Ruxolitinib will be made available to appropriate patients immediately, according to a statement from Incyte, which markets the drug. The company noted that ruxolitinib is the first FDA-approved treatment for this indication.
The approval is based on data from the open-label, single-arm, multicenter REACH1 trial, which studied ruxolitinib in combination with corticosteroids. The 71 patients in the trial had grade 2-4 acute GVHD after allogeneic hematopoietic stem cell transplant; of these patients, 49 were refractory to steroids alone, 12 had received at least two prior therapies for GVHD, and 10 did not otherwise meet the FDA definition of steroid refractory.
The trial’s primary endpoints were day-28 overall response rate and response duration. Among the 49 patients with steroid only–refractory GVHD, the overall response rate was 100% for grade 2 GVHD, 40.7% for grade 3, and 44.4% for grade 4. Median response duration was 16 days. For all 49 of these patients, the overall response rate was 57%, and the complete response rate was 31%.
Among all 71 participants, the most frequently reported adverse reactions were infections (55%) and edema (51%); anemia (71%), thrombocytopenia (75%), and neutropenia (58%) were the most common laboratory abnormalities.
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.