User login
PREVENT: AHA’s new risk calculator incorporates CKM health
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
The new Predicting Risk of CVD Events (PREVENT) calculator is the first risk calculator that combines measures of cardiovascular, kidney, and metabolic health to estimate risk for CVD.
It follows an AHA presidential advisory and scientific statement published in October, formally defining cardiovascular-kidney-metabolic (CKM) syndrome.
The PREVENT calculator also “starts earlier and goes longer” than the pooled cohort equations (PCE), Sadiya Khan, MD, MSc, chair of the statement writing committee, told this news organization.
PREVENT is for use in adults aged 30-79 years and estimates the 10- and 30-year risk of total CVD including, for the first time, heart failure. The PCE were designed to assess 10-year risk of only myocardial infarction and stroke and only in adults aged 40-79 years.
“The new PREVENT equations are important for doctors because they allow us to start conversations earlier and more comprehensively and accurately calculate risk for our patients,” said Dr. Khan, preventive cardiologist at Northwestern Medicine and associate professor at Northwestern University in Chicago.
“We want to support clinicians in starting these conversations around optimizing CKM health earlier and begin to engage in discussions on ways to optimize health,” Dr. Khan added.
The AHA scientific statement on the PREVENT calculator, with Dr. Khan as lead author, was published online in Circulation, with an accompanying article that describes development and validation of the tool.
Going beyond the PCE
The new calculator was developed using health information from more than 6 million adults from diverse racial and ethnic, socioeconomic, and geographic backgrounds.
In addition to blood pressure and cholesterol levels, the PREVENT equations allow for inclusion of hemoglobin A1c, if necessary, to monitor metabolic health.
It also includes estimated glomerular filtration rate (eGFR), a measure of kidney function, and allows for use of albumin excretion to monitor kidney disease to further individualize risk assessment and help inform personalized treatment options.
The new calculator also asks about tobacco use and use of medications for CVD risk factors and factors in age and sex, and it removes race from the risk calculations.
“The inclusion of race in risk prediction may imply that differences by race are not modifiable and may reify race as a biological construct, which may worsen health disparities. Therefore, it was decided a priori not to include race as a predictor in the development of PREVENT,” the writing group said.
They emphasized that the PREVENT calculator has similar accuracy among varied racial and ethnic groups.
The equations include an option to use the Social Deprivation Index, which incorporates measures of adverse social determinants of health such as education, poverty, unemployment, and factors based on a person’s environment.
The PREVENT equations are a “critical first step” toward including CKM health and social factors in risk prediction for CVD, Dr. Khan said in a news release.
“We are working on finalizing the online tool and it should be available soon – hopefully in a few weeks,” Dr. Khan told this news organization.
Knowledge gaps
The scientific statement lists several knowledge gaps and areas for more research. These include:
- Incorporating “net benefit” to identify the expected benefit of treatment recommendations based on an individual’s level of risk.
- Collecting more data from people of diverse race and ethnic backgrounds to better represent the increasing diversity in the United States. The number of Hispanic and Asian people included in the PREVENT datasets is lower than national estimates in the general U.S. population, so risk estimations in these populations may be less precise.
- Expanding the collection, reporting, and standardization of social determinants of health data, such as individual information rather than neighborhood information.
- Expanding risk assessment and prevention to earlier in life (childhood and/or adolescence) and in key life periods, such as during the peripartum period, since adverse pregnancy outcomes are associated with increased CVD risk.
- Investigating whether predicting adverse kidney outcomes, particularly among people with and without type 2 diabetes, may further optimize cardiovascular risk prediction.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA. Dr. Khan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Already-available drug could help treat type 1 diabetes
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
“I think we have lots of potential to improve people’s quality of life who are living with type 1 diabetes if we can increase their endogenous insulin secretion. ... I think long-term combination therapy is going to be the answer,” study author Emily K. Sims, MD, a pediatric endocrinologist at Indiana University, Indianapolis, said in an interview.
DFMO inhibits the polyamine biosynthesis pathway, which plays a role in the inflammatory responses in autoimmune diseases, including type 1 diabetes. It’s sold under the name eflornithine as an intravenous treatment for African sleeping sickness (trypanosomiasis) and as a cream for unwanted hair growth in women. It also has orphan designations for treating various cancers, including neuroblastoma.
In type 1 diabetes, the immune system destroys insulin-producing pancreatic beta cells. Insulin treatment is required. Recently, the monoclonal antibody teplizumab (Tzield, Sanofi) was approved as a treatment for delaying the onset of type 1 diabetes in people with autoantibodies that signify a preclinical stage of the condition. As yet, no agent has been approved for preserving beta-cell function after the onset of type 1 diabetes, but many are under investigation.
The new safety study by Dr. Sims and colleagues, which was published in Cell Medicine Reports, enrolled 41 people with type 1 diabetes who had been diagnosed within the previous 8 months, including 31 children. Participants were randomly assigned to undergo oral treatment with DFMO at one of five doses or placebo for 3 months, with 3 additional months of follow-up.
Following a mixed-meal tolerance test at 6 months, the C-peptide area under the curve – a measure of beta-cell function – was significantly higher with the three highest DFMO doses compared to placebo (P = .02, .03, and .02 for 125 mg/m2, 750 mg/m2, and 1,000 mg/m2, respectively).
Two individuals dropped out, one because of anaphylaxis. There were no dose-limiting toxicities or serious adverse events, while mild gastrointestinal events, anemia, and headache were common. “Although there’s no [Food and Drug Administration] approval for the oral form right now, there’s a lot of safety data, including in kids from the neuroblastoma studies,” Dr. Sims explained.
There were no differences in C-peptide at 3 months or in hemoglobin A1c at any time point. Glucose areas under the curve were significantly lower for DFMO, compared with placebo in the 125-mg/m2 and 750-mg/m2 treatment groups at the 6-month time point (P = .03 and .04, respectively).
In their article, Dr. Sims and colleagues also reported confirmatory analyses in mice, as well as testing in the humans showing that there didn’t appear to be significant immune system modulation. “So, we can envision giving DFMO in addition to something that targets the immune system, as a combination therapy,” said Dr. Sims, who also worked on the pivotal study of teplizumab.
“I’m excited. The sample size is small, so I was kind of expecting no efficacy signals. ... It’s definitely worth following up,” she said.
However, she noted, “it wasn’t a slam-dunk huge effect. It was subtle. It seemed that things were kind of more stable compared to placebo over time versus ... a big increase in C-peptide over time.”
But, she added, “I believe that even teplizumab will need to be used in combination. It delays the onset of type 1 diabetes and improves C-peptide, but it didn’t get everyone off insulin. I don’t think we’ve seen any drug that won’t need to be used in combination.”
Dr. Sims pointed to other investigational agents, such as verapamil and various Janus kinase inhibitors, that may also serve in combination to forestall or reduce insulin dependency for people with either new-onset type 1 diabetes or those who have been identified via screening as having type 1 diabetes–related autoantibodies. “I think there are a lot of potential different interventions.”
Dr. Sims and colleagues are now conducting a larger six-center JDRF-funded study of DFMO in early-onset type 1 diabetes that will be fully powered and that will use the highest tolerated doses from the preliminary study.
She believes there will likely be benefit even if the agent doesn’t completely reverse the disease. “The people who are making more insulin are just easier to manage, with more time in range and less hypoglycemia.” Even if the drugs only delay but don’t prevent type 1 diabetes entirely in those at risk, “the improvement in quality of life of being able to delay insulin for a few years is really palpable. ... I’m really optimistic.”
Dr. Sims disclosed no relevant financial relationships. Three other authors are coauthors on a patent application for the use of DFMO for the treatment of beta-cell dysfunction in type 1 diabetes; one of those three authors is an employee of Cancer Prevention Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM CELL MEDICINE REPORTS
Alternative antirejection regimen is efficacious in pediatric heart transplant
Study challenges everolimus boxed warning
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
Study challenges everolimus boxed warning
Study challenges everolimus boxed warning
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
according to the first phase 3 trial to compare antirejection strategies in the pediatric setting.
Even though MMF and tacrolimus have never been evaluated for pediatric cardiac transplant in a controlled trial, this combination is widely considered a standard based on adult data, said Christopher Almond, MD, a professor of pediatric cardiology at Stanford (Calif.) Medicine.
Everolimus has not been widely used in an antirejection regimen in children following heart transplant in part because of a boxed warning. The warning was added to labeling when this agent was associated with increased infection and increased mortality in adults if given within 3 months of transplant.
In this non-inferiority trial, called TEAMMATE, patients were randomized to the MMF-based or everolimus-based regimen 6 months after transplant.
Everolimus- vs. MMF-based antirejection
The study enrolled 210 children and adolescents 21 years of age or younger. The control arm treatment consisted of MMF (660 mg/m2 every 12 hours) plus standard dose of tacrolimus (initially 7-10 ng/mL followed at 6 months by 5-8 ng/mL).
In the experimental arm, patients received everolimus (3-8 ng/mL) plus a low dose of tacrolimus (initially 3-5 ng/mL followed at 6 months by 2.5-4.5 ng/mL).
The primary endpoint was score on the major adverse transplant event (MATE-6) tool. Based on gradations of severity, this assigns values for cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), acute cellular rejection (ACR), antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder (PTLD).
Thirty months after randomization, the MATE-6 scores were 1.96 in the everolimus group and 2.18 in the MMF group, which conferred the everolimus-based regimen with a numerical but not a significant advantage over the MMF-based regimen. For the goal of noninferiority, the everolimus regimen “met the prespecified safety criterion for success,” Dr. Almond said.
Numerical advantage for everolimus on efficacy
The primary efficacy endpoint was the MATE-3 score, which is limited to CAV, CKD, and ACR. Again, the mean score on this metric (0.93 vs. 1.25) was lower on the everolimus-based regimen but not significantly different.
Looking at specific events in the MATE-6 score, the everolimus-based regimen was associated with lower numerical rates of CAV and CKD, but a higher rate of PTLD, Dr. Almond reported.
On the MATE-3 efficacy analysis, the everolimus-based regimen was again associated with lower numerical rates of CAV and CKD but higher rates of ACR.
In terms of adverse events, including those involving the gastrointestinal tract, blood cells, proteinuria, and interstitial lung disease, most did not differ markedly even if many were numerically more common in the MMF-based arm. The exception was aphthous stomatitis, which was more common on everolimus (32% vs. 7%; P < .001). There were more discontinuations for an adverse event in the MMF arm (21% vs. 12%; P < .001).
Other differences included a lower proportion of patients in the everolimus arm with anti-HLA antibodies (17% vs. 30%; P < .05). Total cholesterol levels at the end of the study were lower but not significantly different in the MMF group, while the higher median glomerular filtration rate was higher on everolimus, and this did reach statistical significance (P < .05).
Infection rates overall were similar, but cytomegalovirus (CMV) infection was more common on the MMF-based regimen. The 30% lower rate of CMV infection in the everolimus proved to be potentially clinically meaningful when it was considered in the context of MATE-3. When these two endpoints were combined (MATE-3 and CMV infection as a prespecified secondary endpoint, the difference was statistically significant (P = .03) in favor of the everolimus-based regimen,
Study supports safety of everolimus regimen
The take-home message is that the everolimus-based regimen, which “is safe in children and young adults when initiated at 6 months after transplant,” can be considered as an alternative to MFF, Dr. Almond concluded.
However, one of the coauthors of the study, Joseph Rossano, MD, chief of the division of cardiology, Children’s Hospital of Philadelphia, suggested a stronger message.
“These data provide compelling reasons to consider initiation of the combination of everolimus and tacrolimus at 6 months post transplant in pediatric heart transplant recipients,” Dr. Rossano said.
Even though the everolimus-based regimen met the terms of noninferiority overall, patients who received this combination rather than the MMF-based regimen “were less likely to have the combined endpoints of vasculopathy, CKD, rejection and CMV infection. Additionally, they were less likely to make donor specific antibodies,” he said.
He also said that this study challenges the current boxed warning for everolimus. He pointed out that the warning, based on early use of everolimus in adults, does not appear to be an issue for children treated at 6 months.
Early mortality based on infection “was not observed in our study,” he said.
The AHA-invited discussant, Antonio G. Cabrera, MD, division chief of pediatric cardiology, University of Utah, Salt Lake City, drew the same conclusions. Based on the study, the everolimus-based regimen can only be described as noninferior to the MMF-based regimen, but Dr. Cabrera listed the same relative advantages as Dr. Rossano, including better kidney function.
Overall, either regimen might be more appealing based on several variables, but Dr. Cabrera said these data suggest everolimus-based treatment “should be considered” as one of two evidence-based options,
Dr. Almond reported no potential financial conflicts of interest. Dr. Rossano reports financial relationships with Abiomed, Bayer, Cytokinetics, Merck, and Myokardia. Dr. Cabrera reported no potential financial conflicts of interest.
FROM AHA 2023
Revisiting the role of hydrocortisone, fludrocortisone in septic shock
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Switching Patients From a Triptan to a Gepant for Acute Migraine Care and Effective Preventives
Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
How do you switch a patient from a triptan to a gepant?
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the
triptan is not working well for them or they have significant adverse events, I will move
on.
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin.
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of
patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.
Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),
which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.
Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor.
The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.
Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
How do you switch a patient from a triptan to a gepant?
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the
triptan is not working well for them or they have significant adverse events, I will move
on.
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin.
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of
patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.
Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),
which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.
Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor.
The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.
Dr. Rapoport: Most patients who come into my office today, even those whom I have
treated for the last 30 years for acute care of migraine attacks, are taking 1 of the 7
triptan medications available. They might be taking triptans as a tablet—the most
common form—as a nasal spray, or by injection; however, not all patients are suited for
triptans, and sometimes, the need arises to switch to a different class of medication for
treating migraine acutely.
What are the reasons patients switch from a triptan to a gepant?
For some patients, triptans are not working well enough or are causing adverse events.
Other patients have developed cardiac risk factors such as elevated blood pressure,
obesity, smoking, and/or lack of exercise. I am always concerned about constriction of
the coronary blood vessels. Patients who already have some cardiac risk factors and
those who have some actual cardiac disease or have had a previous heart attack
already have constriction of their blood vessels and are not candidates for triptans, as
they are contraindicated.
How do you switch a patient from a triptan to a gepant?
It is important to have some discussion with the patient before the switch. For example,
if a patient with no cardiac risk factors comes into the office asking about this new
medicine, I will ask them several questions about their triptan to ensure it works well
enough (ie, to ascertain if the patient’s migraines improve within 30 to 60 minutes and
are much better within 2 hours of taking the medication). I want to be sure that they do
not have any adverse events related to the triptan, such as chest pain, drowsiness, or
dizziness. I like to ensure that whatever they are taking works long enough—at least 24
hours, preferably 48 hours—so they no longer have a headache, especially the next
day. If the headache comes back the next day, they must re-treat. If I determine the
triptan is not working well for them or they have significant adverse events, I will move
on.
Gepants are small-molecule calcitonin gene-related peptide (CGRP) receptor
antagonists, which are pills that only last for 2 to 3 days in the body. There are 2
gepants for acute care and 2 for the prevention of migraine. The first gepant approved
by the US Food and Drug Administration (FDA) for acute care was ubrogepant
(Ubrelvy), which comes in 2 sizes, 50 mg or 100 mg tablets. I sometimes start with 50
mg, but for the more difficult migraine patient, I will start with 100 mg. If the medicine is
not doing a complete job within 2 hours, the patient may take a second dose, up to 200
mg. Some adverse events may include nausea or slight drowsiness. The patient should
avoid certain medicines such as antifungal medicines (eg, ketoconazole, itraconazole)
and certain antibiotics like clarithromycin.
Another gepant, rimegepant (Nurtec), comes in only 1 size, a 75-mg oral disintegrating
tablet, which can be used both for acute care of migraine and for prevention. Patients
can take a tablet as soon as their migraine attack begins, and they are not to repeat it
that day. If the headache does not go away in 2 hours, I want them to then take a triptan
and an anti-inflammatory drug (there is no contraindication to mix these drugs). I want
them to try it at least 1 more time, encouraging patients to take it early, right at the start
of the headache. If the medicine is still not working by the second or third time, they
should stop using it. Preventively, patients take 75 mg every other day, which can be
quite effective. Side effects are slight nausea and some abdominal pain or dyspepsia.
A third gepant is atogepant (Qulipta), which is only for migraine prevention. It comes in
10 mg, 30 mg, and 60 mg and is taken once every day as a preventive. It can cause
some drowsiness, constipation, and nausea.
Are there any other acute care drugs you recommend if triptans are not working?
Yes, there is another drug class called the ditans. These medications work very well but
have more adverse events associated with them than I like. A higher percentage of
patients seem to be pain-free in 2 hours when using a ditan; however, the only one
available, lasmiditan (Reyvow), has never been studied against a gepant, so I cannot
say if one is better than the other. Lasmitidan works similarly to a triptan by stimulating
serotonin 1F receptors but does not constrict blood vessels. Up to 15% of patients have
dizziness and up to 7% have drowsiness, so patients should not drive within 8 hours
after taking lasmiditan. This medication is available in 2 sizes, 100 mg and 200 mg. I
usually give patients a 200-mg dose, which is good enough for 24 hours. Ditans are a
Schedule V drug, meaning some patients might take more than they should because it
makes them feel good. It can be a challenging drug to get, but it is an excellent acute
care drug when none of the mentioned adverse events occur.
Which preventive drugs do you tend to prescribe your patients for migraine since
triptans are not preventive?
For many years, we have used some of the older preventives. Antidepressants can be
an option for preventive treatment of migraine. Amitriptyline, a tricyclic antidepressant, is
a pretty good medicine. However, it has a lot of adverse events associated with it,
including dry mouth, weight gain, and drowsiness, so patients who take this at night
often sleep better. The dose is 10 mg to 50 mg taken before bed. This drug is often
used, but I would not say I like to prescribe it as much as other medications, even
though amitriptyline is effective and likely to work by affecting the level of serotonin and
other chemicals in the brain. There is little evidence that other classes of
antidepressants, such as selective serotonin reuptake inhibitors and serotonin and
norepinephrine reuptake inhibitors, are effective for migraine prevention. Adverse
effects may include weight gain, fatigue, constipation, and dry mouth, making it difficult
for a patient to stick with treatment.
Beta blockers are another preventive medication option for migraine. Beta blockers are
best known as a medical treatment for cardiovascular conditions, such as hypertension,
stable or unstable angina, and congestive heart failure. Beta blockers prevent the stress
hormone adrenaline (epinephrine) from binding to beta receptors, slowing heart rate
and lowering blood pressure. A commonly used beta blocker is propranolol (Inderal),
which also comes in a long-acting preparation. Doses range from 60 mg to 180
mg. Other beta blockers effective for migraine prevention include metoprolol, nadolol,
and atenolol.
Many of my patients are young, healthy females who like to exercise. Most report that
their heart rate is slow, they get short of breath, and they cannot exercise as effectively
while on a beta blocker. It also takes about 2 months until this medication starts
working. Patients may feel as if they are having too many adverse events, so I start
them on a very low dose and build it up gradually for a month and see how they are
feeling.
Epilepsy medicines can also be used to prevent migraine. There are 2 common
epilepsy medications. Topiramate (Topamax) doses can range from 75 mg to 100 mg
and are sometimes higher. Topiramate is a good medicine, but there are many potential
adverse events: tingling in the extremities, difficulty finding words when speaking,
confusion, raised eye pressure, and others. Divalproex sodium (Depakote) is another
popular medication, available in 500 mg to 1000 mg doses. This medicine can cause
some endocrine problems in women and can also damage the spinal cords of a fetus,
so this drug should not be taken during early pregnancy.
Monoclonal antibodies against CGRP are a strong preventive medication and a new
class of drugs that were first approved by the FDA in 2018. They are designed to
prevent episodic migraine (up to 14 headache days per month), chronic migraine (15 or
more headache days per month) and seem to work when a patient has medication
overuse headaches. CGRP is a neuropeptide involved in many body processes,
including blood pressure regulation, tissue repair, wound healing, and inflammation, and
is a potent vasodilator. When CGRP is released in the brain, it affects the trigeminal
nerve, increasing pain transmission and sensitivities to touch and temperature. CGRP
also causes inflammation and pain that happen during a migraine; it makes headache
pain worse and causes headaches to last longer.
Some CGRP inhibitors block CGRP from binding to CGRP receptors, a key contributor
to the trigeminal nerve pain and inflammation of migraine, while some grab the CGRP
and prevent it from activating the receptor.
The 2 classes of these drugs are monoclonal antibodies against CGRP and small
molecule CGRP antagonists. Fortunately, CGRPs have long half-lives and work for 1 to
3 months. The CGRP monoclonal antibodies are large molecule drugs. There are 4
different types, and 2 of them are injected by the patient at home once a month. One
can be injected at home once a month or every 3 months. For the latter option, patients
need to triple up with 3 injections in one day, so they do not have to inject for 3 months.
The fourth CGRP is an intravenous infusion that can be administered in an infusion
center or at home. This one is more inconvenient, but it is a strong drug. The small
molecule CGRP antagonists are taken by mouth in pill form. All CGRPs have been
shown to decrease the number of headaches per month.
The main goal of preventive therapy is to lessen the impact of migraines on patients’
lives by reducing how often they occur, how severe they are, and how long they last.
Preventive therapy also decreases disability and improves patients’ functioning over
time. Preventive therapy can help keep the costs for migraine care down by reducing
the need for acute treatments and allowing the patient to keep working or taking care of
their kids. Furthermore, preventive medications can make acute migraine treatments
more effective and help avoid the overuse of acute medications.
Infographic: Careers that tempt doctors to leave medicine
In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?
For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.
A version of this article first appeared on Medscape.com.
In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?
For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.
A version of this article first appeared on Medscape.com.
In a recently published Medscape report, 26% of American physicians said they were considering a career away from practicing medicine, for various reasons. Becoming a teacher was one of the nonclinical careers that most enthused them. What were the others?
For more details, check out the Medscape Physicians and Nonclinical Careers Report 2023.
A version of this article first appeared on Medscape.com.
Memory-enhancing intervention may help boost confidence, not necessarily memory, in older adults, study suggests
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GSA 2023
Use the stool! Fecal microbiota transplants help kids with diarrheal infection
(AAP).
However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.
C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.
An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.
The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.
“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.
An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.
No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.
Unlike pediatric data, adult data come from a randomized clinical trial.
“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study.
Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work.
Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult.
“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.
Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.
The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.
“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.
Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.
A version of this article appeared on Medscape.com.
(AAP).
However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.
C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.
An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.
The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.
“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.
An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.
No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.
Unlike pediatric data, adult data come from a randomized clinical trial.
“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study.
Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work.
Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult.
“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.
Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.
The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.
“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.
Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.
A version of this article appeared on Medscape.com.
(AAP).
However, fecal microbiota transplants (FMTs) should not be used to treat other gastrointestinal ailments such as Crohn’s disease or ulcerative colitis, because scientific evidence falls short on effectiveness in treating these conditions, the group said.
C. difficile infections (CDIs) are major contributors to hospital-associated diarrhea and diarrhea caused by antibiotics. An FMT involves introducing the feces of a healthy person into the gastrointestinal tract, usually through a nasogastric tube but sometimes in capsules containing healthy stool. Serious adverse reactions associated with an FMT, such as hospitalization, are rare, occuring in roughly 2% of case, the AAP said.
An FMT “does have a place for treatment of recurrent CDIs in children,” said Maria Oliva-Hemker, MD, a pediatric gastroenterologist at Johns Hopkins University School of Medicine in Baltimore and the lead author of the report, which was online in Pediatrics.
The AAP strongly encourages people not to perform an FMT at home, although caregivers may be tempted due to a lack of medical facilities located nearby to deliver this care.
“People might see a video on YouTube and think they can do this themselves,” Dr. Oliva-Hemker said.
An FMT requires screening of donors for any infections, which involves administering questionnaires and analyzing donor blood and stool, which are tasks better suited for medical facilities than for a living room.
No controlled or prospective clinical trials on the efficacy of FMT for children exist, according to the AAP. But a retrospective study published in 2020 showed that one or two courses of FMT prevented CDI recurrence in children 87% of the time. Researchers defined the eradication of CDIs as no recurrence for at least 2 months after an FMT and noted the success rates in children were comaparable to those reported in adults.
Unlike pediatric data, adult data come from a randomized clinical trial.
“Sometimes, kids are the last people to be enrolled in these trials,” said Maribeth Nicholson, MD, MPH, a pediatric gastroenterologist at Vanderbilt University Medical Center in Nashville, Tenn., an author of the 2020 study.
Dr. Nicholson, who was not involved in the AAP report, said that the retrospective data are strong enough to justify using FMT to eradicate CDIs in children. But researchers are unclear about the biologic mechanisms that make FMTs work.
Dr. Nicholson said that many therapeutics meant to produce a healthier microbiome are being studied in clinical trials. Any clinical trials of such products should include children, Dr. Nicholson said. A child’s gastrointestinal microbiome is actively developing, Dr. Nicholson added, compared with the relatively stable microbiome of an adult.
“When we think about the microbiome it makes sense to target kids, because they’re more apt to respond to these therapies. I worry that somebody will say ‘this doesn’t work in adults,’ and it just stops there,” Dr. Nicholson said.
Though the AAP said that the benefits of FMT for treating CDIs are clear, the data available for treating other conditions such as ulcerative colitis or Crohn’s disease are less convincing. Any child receiving an FMT for these ailments should only do so as part of a clinical trial, the group said.
The AAP report endorses a joint position paper, published in 2019, about the benefits of FMTs for CDIs from North American and European pediatric gastroenterology societies. Dr. Nicholson was an author of this joint statement and hopes that the AAP report raises further awareness among pediatricians that FMTs are a safe and effective treatment for recurrent CDIs.
“This is something that maybe is not as discussed in pediatric circles. Kids need FMTs sometimes,” Dr. Nicholson said.
Dr. Oliva-Hemker and Dr. Nicholson report no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM PEDIATRICS
WHO: Smoking cessation reduces risk of type 2 diabetes up to 40%
TOPLINE:
, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.
With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
METHODOLOGY:
- The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
- The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
- Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.
TAKEAWAY:
- Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
- Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
- Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
- Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
- Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.
IN PRACTICE:
“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.
“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
SOURCE:
The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.
The detailed policy brief can be downloaded on the IDF website.
LIMITATIONS:
Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.
Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking. However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.
“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
DISCLOSURES:
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.
With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
METHODOLOGY:
- The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
- The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
- Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.
TAKEAWAY:
- Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
- Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
- Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
- Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
- Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.
IN PRACTICE:
“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.
“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
SOURCE:
The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.
The detailed policy brief can be downloaded on the IDF website.
LIMITATIONS:
Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.
Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking. However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.
“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
DISCLOSURES:
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, and quitting even after one has developed type 2 diabetes is important in preventing a worsening of the disease’s many serious comorbidities, according to a new policy brief jointly issued by the World Health Organization, the International Diabetes Federation (IDF), and the University of Newcastle, Callaghan, Australia.
With type 2 diabetes representing one of the most prevalent chronic diseases worldwide and the ninth cause of death globally, the potential to reduce the risk and worsening of the disease by quitting smoking adds to the urgency of smoking cessation as a public health interest.
METHODOLOGY:
- The policy brief summarizes the evidence on the health impacts of type 2 diabetes, tobacco smoking, and the pathophysiology of tobacco use and its role in the development of type 2 diabetes.
- The brief also describes the latest data on newer products that target smokers or potential smokers, including smokeless tobacco, new nicotine and tobacco products, and their relationship with type 2 diabetes. For instance, evidence suggests that even with smokeless tobacco, heavy use or high consumption increases the risk of developing type 2 diabetes, as the products often contain nicotine, known to contribute to the development of type 2 diabetes and related health conditions.
- Evidence on the effectiveness of tobacco control interventions among those with type 2 diabetes is also summarized, including discussion of a systematic review of six studies suggesting that interventions focusing on education and the involvement of health care professionals and pharmacists can be beneficial for people with type 2 diabetes.
TAKEAWAY:
- Smoking exacerbates the known serious complications of diabetic neuropathy and foot ulcers with type 2 diabetes, while further impeding wound healing.
- Smoking also causes damage to retinal blood vessels already at risk with type 2 diabetes, increasing the risk of diabetic retinopathy and vision loss.
- Quitting tobacco use can help prevent those and other major health complications already linked to diabetes, including kidney failure and cardiovascular events.
- Studies show that key misconceptions among smokers with type 2 diabetes that can prevent cessation include concerns about post-cessation weight gain, the influence of peers who smoke, and the psychological aspect of addiction.
- Clinicians are urged to provide advice on how to stop smoking to all tobacco users during the course of a routine consultation or interaction, which can be accomplished in only a few minutes.
IN PRACTICE:
“Health professionals play a vital role in motivating and guiding individuals with type 2 diabetes in their journey to quit tobacco,” Ruediger Krech, MD, director of the Department of Health Promotion at the World Health Organization in Geneva, Switzerland, said in a press statement on the policy brief.
“Simultaneously, governments must take the crucial step of ensuring all indoor public places, workplaces, and public transport are completely smoke-free. These interventions are essential safeguards against the onset and progression of this and many other chronic diseases,” he emphasized.
SOURCE:
The policy brief was jointly developed by the World Health Organization, the International Diabetes Federation, and the University of Newcastle.
The detailed policy brief can be downloaded on the IDF website.
LIMITATIONS:
Research remains limited on some issues, including the effectiveness of tobacco control interventions and smoking cessation methods for people with type 2 diabetes.
Likewise, specific guidelines for smoking cessation in the type 2 diabetes population are lacking. However, the general approaches of building patient motivation, behavioral interventions, and pharmacological treatments are advised.
“These interventions should be at least as intensive as those for the general population, while considering the unique characteristics of the disease and the individual,” the authors asserted.
DISCLOSURES:
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A better way to control blood pressure
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...
What is going on?
The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.
It’s pretty obvious that
We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.
All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.
That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?
At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.
A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.
PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.
At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.
These factors summarize why it works:
- Senior management belief, commitment, and leadership
- Informed buy-in from clinicians and patients
- A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
- An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
- Persistent clinician-patient follow-up
- Refusal to accept failure
Since this approach is so successful, why is its use not everywhere?
It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.
Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.
I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.
Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.
Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.
Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.
For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?
Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.
Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.