User login
Ketamine promising for rare condition linked to autism
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
From Human Genetics and Genomic Advances
Dietary change tops for reducing CVD risk in stage 1 hypertension
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Clozapine may be best choice for cutting SUD risk in schizophrenia
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF PSYCHIATRY
Psychedelics may ease fear of death and dying
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Psychedelics can produce positive changes in attitudes about death and dying – and may be a way to help ease anxiety and depression toward the end of life, new research suggests.
In a retrospective study of more than 3,000 participants,
“Individuals with existential anxiety and depression at end of life account for substantial suffering and significantly increased health care expenses from desperate and often futile seeking of intensive and expensive medical treatments,” co-investigator Roland Griffiths, PhD, Center for Psychedelics and Consciousness Research at Johns Hopkins Medicine, Baltimore, told this news organization.
“The present findings, which show that both psychedelic and non–drug-occasioned experiences can produce positive and enduring changes in attitudes about death, suggest the importance of future prospective experimental and clinical observational studies to better understand mechanisms of such changes as well as their potential clinical utility in ameliorating suffering related to fear of death,” Dr. Griffiths said.
The results were published online Aug. 24 in PLOS ONE.
Direct comparisons
Both psychedelic drug experiences and near-death experiences can alter perspectives on death and dying, but there have been few direct comparisons of these phenomena, the investigators note.
In the current study, they directly compared psychedelic-occasioned and nondrug experiences, which altered individuals’ beliefs about death.
The researchers surveyed 3,192 mostly White adults from the United States, including 933 who had a natural, nondrug near-death experience and 2,259 who had psychedelic near-death experiences induced with lysergic acid diethylamide, psilocybin, ayahuasca, or N,N-dimethyltryptamine.
The psychedelic group had more men than women and tended to be younger at the time of the experience than was the nondrug group.
Nearly 90% of individuals in both groups said that they were less afraid of death than they were before their experiences.
About half of both groups said they’d encountered something they might call “God” during the experience.
Three-quarters of the psychedelic group and 85% of the nondrug group rated their experiences as among the top five most personally meaningful and spiritually significant events of their life.
Individuals in both groups also reported moderate- to strong-lasting positive changes in personal well-being and life purpose and meaning after their experiences.
However, there were some differences between the groups.
More research needed
Compared with the psychedelic group, the nondrug group was more likely to report being unconscious, clinically dead, or that their life was in imminent danger.
The nonpsychedelic group was also more likely to report that their experience was very brief, lasting 5 minutes or less.
Both the psychedelic and nondrug participants showed robust increases on standardized measures of mystical and near-death experiences, but these measures were significantly greater in the psychedelic group.
The survey findings are in line with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis.
This includes a 2016 study by Dr. Griffiths and colleagues, which included 51 patients with late-stage cancer. As reported at the time, results showed a single, high dose of psilocybin had rapid, clinically significant, and lasting effects on mood and anxiety.
Limitations of the current survey cited by the researchers include the use of retrospective self-report to describe changes in death attitudes and the subjective features of the experiences. Also, respondents were a self-selected study population that may not be representative of all psychedelic or near-death experiences.
In addition, the study did not attempt to document worldview and other belief changes, such as increased belief in afterlife, that might help explain why death attitudes changed.
Looking ahead, the researchers note that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
Support through the Johns Hopkins Center for Psychedelic and Consciousness Research was provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation. Funding was also provided by the Y.C. Ho/Helen and Michael Chiang Foundation. The investigators have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
ACC/AHA issue chest pain data standards update to 2021 guideline
The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.
In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.
The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.
“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.
“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”
In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.
“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.
The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.
Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.
The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.
Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.
Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.
Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.
The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.
Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”
“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.
This research had no commercial funding. The authors have no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.
In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.
The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.
“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.
“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”
In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.
“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.
The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.
Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.
The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.
Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.
Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.
Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.
The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.
Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”
“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.
This research had no commercial funding. The authors have no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology/American Heart Association have issued a set of data standards for chest pain and acute myocardial infarction to accompany the 2021 guidelines for evaluation and diagnosis of chest pain.
In October 2021, the AHA/ACC issued a joint clinical practice guideline encouraging clinicians to use standardized risk assessments, clinical pathways, and tools to evaluate and communicate with patients who present with chest pain, as reported by this news organization.
The writing group underscored the need to reach a consensus for the definitions of chest pain. The new document standardizes related data elements for consistent reporting on chest pain syndromes.
“This is an appendix to the guidelines and a planned effort to try to harmonize and bring uniformity to the language applied,” writing committee chair H.V. “Skip” Anderson, MD, with UT Health Science Center, Houston, told this news organization.
“You want heart attack to mean the same thing in Miami Beach as in Western Pennsylvania, as in Oregon and Washington and every place in between,” Dr. Anderson explained. “You want everybody to be using the same language, so that’s what these data standards are meant to do.”
In the document, data elements are grouped into three broad categories: chest pain, myocardial injury, and MI.
“We deliberately followed the plans contained in the new guideline and focused on potentially serious cardiovascular causes of chest pain as might be encountered in emergency departments,” the writing group notes in the document.
The terms “typical” and “atypical” as descriptors of chest pain or anginal syndromes are not used in the new document, in line with the 2021 guidance to abandon these terms.
Instead, the new document divides chest pain syndromes into three categories: “cardiac,” “possible cardiac,” and “noncardiac” – again, in keeping with the chest pain guideline.
The document also includes data elements for risk stratification scoring according to several common risk scoring algorithms and for procedure-related myocardial injury and procedure-related MI.
Each year, chest pain sends more than 7 million adults to the emergency department in the United States. Although noncardiac causes of chest pain make up a large majority of these cases, there are several life-threatening causes of chest pain that must be identified and treated promptly.
Distinguishing between serious and nonserious causes of chest pain is an urgent imperative, the writing group says.
Overall, they say this new clinical lexicon and set of data standards should be “broadly applicable” in various settings, including clinical trials and observational studies, patient care, electronic health records (EHRs), quality and performance improvement initiatives, registries, and public reporting programs.
The 2022 ACC/AHA Key Data Elements and Definitions for Chest Pain and Acute Myocardial Infarction was simultaneously published online in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
It was developed in collaboration with the American College of Emergency Physicians and the Society for Cardiac Angiography and Interventions and endorsed by the Society for Academic Emergency Medicine.
Dr. Anderson noted that “almost all of the guidelines that come out now, certainly in the last few years, have been followed after a certain interval by a set of data standards applicable to the guidelines.”
“It would be really great if it could actually be attached as an appendix, but the nature of the development of these things is such that there will always be a bit of a time lag between the writing group that develops the guidelines and the work group that develops the data standards; you can’t really have them working in parallel at the same time,” Dr. Anderson said in an interview.
This research had no commercial funding. The authors have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Candy, desserts: A ‘gateway’ to unhealthy eating among teens
Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.
“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.
“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.
Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.
Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Blame the pandemic?
Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.
For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).
More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.
During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.
Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.
During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.
The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.
Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
Not all UPFs are bad
“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.
“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.
Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”
“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.
Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.
“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.
The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.
“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.
“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.
Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.
Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Blame the pandemic?
Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.
For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).
More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.
During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.
Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.
During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.
The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.
Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
Not all UPFs are bad
“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.
“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.
Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”
“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.
Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.
“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.
The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Certain ultraprocessed foods – especially candy, prepackaged pastries, and frozen desserts – could be “gateway foods” for adolescents, leading them to increase their intake of other unhealthy foods, a new study suggests.
“For teens, gateway ultraprocessed foods (candy, store pastries, frozen desserts) should be prioritized for preventive dietary interventions as they increase intake across all other UPFs,” lead researcher Maria Balhara said in an interview.
“The good news,” said Ms. Balhara, is that even small changes, such as reducing how often gateway foods are consumed, may reduce overall intake of unhealthy foods and have a “big impact” on overall health.
Ms. Balhara has a unique perspective on adolescent eating habits: She’s 16 years old, from Florida, and conducted the study while dual-enrolled at Broward College and Cooper City High School.
Her study was released Sept. 7 ahead of presentation at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Blame the pandemic?
Over the past 30 years, there’s been a steady increase in consumption of UPFs worldwide, coupled with mounting evidence that diets rich in UPFs raise the risk for several chronic diseases, including weight gain, hypertension, and increased risk for heart disease and premature death.
For her research, Ms. Balhara asked 315 teenagers (42% male) from 12 high schools in South Florida how often they consumed UPFs over two time periods – before COVID in 2019 and after COVID restrictions were eased in 2022 – using a survey that she developed called the Processed Intake Evaluation (PIE).
More than 2 in 5 teens (43%) increased their consumption of UPFs between 2019 and 2022.
During this time, increased consumption of frozen desserts was associated with an 11% increase in consumption of all other UPFs, whereas increased consumption of prepackaged pastries and candy was associated with a 12% and 31%, respectively, increase in consumption of all other UPFs, Ms. Balhara found.
Encouragingly, 57% of teens decreased their consumption of UPFs between 2019 and 2022.
During this time, decreased consumption of processed meats was associated with an 8% decrease in consumption of all other UPFs, whereas decreased consumption of white bread and biscuits was associated with a 9% and 10%, respectively, decrease in consumption of all other UPFs.
The results provide initial evidence for a new “gateway food model,” Ms. Balhara told this news organization, in which certain UPFs, when increased, drive overall consumption of all UPFs among teens.
Limitations of the study include the self-reported dietary data and the fact that the PIE survey has not been validated.
Not all UPFs are bad
“I commend Ms. Balhara for her project, which highlights the importance of establishing good dietary patterns early in life,” Donna K. Arnett, PhD, past president of the AHA, said in a news release.
“The relationship between poor dietary quality and cardiovascular risk factors is well-established. While this is a small, preliminary study, it’s an important topic to continue to investigate and help us understand ways we can influence dietary behaviors to promote optimal cardiovascular health for all ages,” said Dr. Arnett, executive vice president for academic affairs and provost at the University of South Carolina, Columbia.
Offering perspective on the study, Taylor C. Wallace, PhD, with the department of nutrition and food studies, George Mason University, Fairfax, Va., made the point that “food processing and ultraprocessed foods aren’t the problem. The problem is the types of ultraprocessed foods on the market that people consume.”
“Remember, non-fat, vitamin D fortified yogurt is also ‘ultra-processed,’ and it’s very healthy,” he told this news organization.
Dr. Wallace said that it’s no surprise that teens increased their intake of UPFs during the pandemic.
“Of course, people increased processed food intake during the pandemic. Processed foods are shelf stable at a time when grocery stores were running out of things and supply chains weren’t able to keep up. Also, many were depressed and use food to indulge,” he noted.
The study had no funding. Ms. Balhara has no relevant disclosures. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and an advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2022
Reassuring data on NSAIDs in IBD flares
A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.
Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.
“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.
“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.
The study was published online in the American Journal of Gastroenterology.
Taking a second look
Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.
To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.
First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.
However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).
The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.
The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.
While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.
They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
Good study, reassuring data
“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.
Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”
Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.
“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.
“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.
NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.
In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”
Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.
“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.
The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.
Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.
“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.
“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.
The study was published online in the American Journal of Gastroenterology.
Taking a second look
Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.
To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.
First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.
However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).
The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.
The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.
While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.
They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
Good study, reassuring data
“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.
Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”
Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.
“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.
“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.
NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.
In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”
Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.
“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.
The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study has found no convincing evidence to suggest a causal relationship between nonsteroidal anti-inflammatory drug (NSAID) use and inflammatory bowel disease (IBD) exacerbations.
Rather, the study suggests that observed associations between IBD exacerbation and NSAID exposure may be explained by preexisting underlying risks for IBD flares, residual confounding, and reverse causality.
“We hope these study findings will aid providers in better directing IBD patients on their risk for IBD exacerbation with NSAID use,” write Shirley Cohen-Mekelburg, MD, with University of Michigan Medicine, Ann Arbor, and colleagues.
“This may guide therapy for both IBD and non-IBD related pain management, and the comfort of patients with IBD and the clinicians who treat them when considering NSAIDs as a non-opioid treatment option,” they add.
The study was published online in the American Journal of Gastroenterology.
Taking a second look
Patients with IBD (Crohn’s disease and ulcerative colitis) are prone to both inflammatory and noninflammatory pain, and there has been long-standing concern that NSAIDs may play a role in disease flare-ups.
To see whether a true association exists, Dr. Cohen-Mekelburg and colleagues conducted a series of studies that involved roughly 35,000 patients with IBD.
First, they created a propensity-matched cohort of 15,705 patients who had received NSAIDs and 19,326 who had not taken NSAIDs. Findings from a Cox proportional hazards model suggested a higher likelihood of IBD exacerbation in the group that had taken NSAIDs (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33), after adjusting for age, gender, race, Charlson comorbidity index, smoking status, IBD type, and use of immunomodulator or biologic medications.
However, those who received NSAIDs were already at increased risk of experiencing a disease flare. And the prior event rate ratio for IBD exacerbation, as determined by dividing the adjusted HR after NSAID exposure by the adjusted HR for pre-NSAID exposure, was 0.95 (95% CI, 0.89-1.01).
The researchers used a self-controlled case series to verify their findings and to adjust for other immeasurable patient-level confounders. In this analysis, which involved 3,968 patients, the risk of IBD flare did not increase in the period from 2 weeks to 6 months after exposure to an NSAID.
The incidence of IBD exacerbations was higher in the 0- to 2-week transition period after an NSAID was prescribed, but it dropped after the 2-week “risk” window. This suggests that these short-term flares may be secondary to residual confounding related to reverse causality, rather than the NSAIDs themselves, the researchers say.
While NSAIDs represent the most common first-line analgesic, their use for patients with IBD is variable, in part due to the suspected risk of IBD exacerbation “despite inconclusive evidence of harm to date,” Dr. Cohen-Mekelburg and colleagues note.
They also note that about 36% of patients with IBD in their cohort received at least one NSAID prescription, and three-quarters of these patients did not experience an IBD exacerbation during an average of 5.9 years of follow-up.
Good study, reassuring data
“This is a good study trying to understand the potential sources of bias in associations,” Ashwin Ananthakrishnan, MD, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.
Overall, he said the study “provides reassurance that cautious, short-duration or low-dose use is likely well tolerated in most patients with IBD. But more work is needed to understand the impact of higher dose or more frequent use.”
Also weighing in, Adam Steinlauf, MD, with Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, noted that patients with IBD experience pain throughout the course of their disease, both intestinal and extraintestinal.
“Treating the underlying IBD is important, but medications used to treat joint pain and inflammation specifically are few,” said Dr. Steinlauf, who wasn’t involved in the new study.
“Sulfasalazine has been used with success, but it does not work in everyone, and many are allergic to the sulfa component, limiting its use. Narcotics are often reluctantly used for these issues as well. Medical marijuana has emerged on the scene to control both types of pain, but to date, there is inconclusive evidence that it significantly treats both pain and underlying inflammation,” Dr. Steinlauf pointed out.
NSAIDs, on the other hand, are “excellent” choices for treating joint pain and inflammation, but gastroenterologists often try to avoid these medications, given the fear of triggering flares of underlying IBD, Dr. Steinlauf told this news organization.
In his view, this new study is “important in that it quite elegantly challenges the notion that gastroenterologists should avoid NSAIDs in patients with IBD.”
Although more data are clearly needed, Dr. Steinlauf said this study “should give practitioners a bit more confidence in prescribing NSAIDs for their patients with IBD if absolutely necessary to control pain and inflammation and improve quality of life when other standard treatments fail.
“The association of NSAIDs with subsequent flares, of which we are all so well aware of and afraid of, may in fact be related more to our patients’ underlying risks for IBD and reverse causality rather than the NSAIDs themselves. Future studies should further clarify this notion,” Dr. Steinlauf said.
The study received no commercial funding. Dr. Cohen-Mekelburg, Dr. Ananthakrishnan, and Dr. Steinlauf have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF GASTROENTEROLOGY
Zeroing in on genes involved in Crohn’s disease
Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.
Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.
“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.
However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.
The study was published online in Nature Genetics.
Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.
To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.
Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.
They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.
Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”
“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.
The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.
The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.
The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.
“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.
Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.
A version of this article first appeared on Medscape.com.
Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.
Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.
“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.
However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.
The study was published online in Nature Genetics.
Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.
To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.
Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.
They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.
Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”
“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.
The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.
The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.
The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.
“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.
Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.
A version of this article first appeared on Medscape.com.
Researchers have identified genetic variants in 10 genes that increase susceptibility to Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Some of the variants had not previously been connected to CD.
Because they’re so common, most people will have some of the genetic variants that increase susceptibility to IBD, first author Aleksejs Sazonovs, PhD, research associate at the Wellcome Sanger Institute, Hinxton, United Kingdom, said in a news release.
“These common variants may increase a person’s risk by 10%, for example, but this increased risk doesn’t necessarily lead to disease,” Dr. Sazonovs explains.
However, some rare variants can render an individual four or five times more likely to develop IBD, “so it’s especially important to locate these and understand the biological processes they disrupt,” Dr. Sazonovs adds.
The study was published online in Nature Genetics.
Genome-wide association studies (GWASs) of CD, and of IBD more generally, have identified more than 200 loci that contribute to disease risk.
To complement GWAS data and to better define actionable biological targets in protein-coding genes, the researchers analyzed large-scale exome sequencing data from more than 30,000 patients with CD and 80,000 control persons from more than 35 centers in the International IBD Genetics Consortium.
Their findings, they say, “directly implicate” genetic variants in 10 genes in general-onset CD, four of which lie within established CD GWAS loci.
They also implicate genetic variation in six genes in regions of the genome that had not previously been connected to CD.
Of note, say the researchers, many of these newly associated genes appear to be linked to the roles that mesenchymal cells (MCs) play in intestinal homeostasis, “a pathway not previously implicated by genetic studies.”
“In addition to reiterating the central role of innate and adaptive immune cells, as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation,” they add.
The researchers note that previous studies have demonstrated that the biology of MCs is disrupted in IBD. The current findings of coding variants in these genes demonstrate that these cells and functions “causally contribute to disease susceptibility,” they write.
The association of these pathways with CD pathogenesis provides a rationale for developing therapeutic modalities that can “reestablish the balance to the mesenchymal niche, as it is believed that genetic evidence for a drug target has a measurable impact on drug development,” they add.
The researchers plan to extend this research to ulcerative colitis and to increase the scale of sampling.
“We’ve already begun working on our next study, which will use exome sequence data from more than 650,000 individuals and give us unprecedented ability to derive insights into the aberrant biology underpinning inflammatory bowel disease,” Carl Anderson, PhD, senior investigator at the Wellcome Sanger Institute, says in the release.
Support for the study was funded by the National Institutes of Health, the Wellcome Trust, and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sazonovs reports no relevant financial relationships. Dr. Anderson has received consultancy fees from Genomics PLC and BridgeBio and lecture fees from GlaxoSmithKline.
A version of this article first appeared on Medscape.com.
FROM NATURE GENETICS
FDA approves Botox challenger Daxxify for frown lines
The U.S. .
According to a company news release, Daxxify, an acetylcholine release inhibitor and neuromuscular blocking agent, is the first peptide-formulated, long-acting neuromodulator approved for this indication.
The approval of Daxxify, manufactured by Revance Therapeutics, was based on the data from the SAKURA phase 3 clinical trial program, which included more than 2,700 adults who received roughly 4,200 treatments, according to the company.
About three-quarters of participants achieved at least a two-grade improvement in glabellar lines at week 4 as judged by both investigator and patient, and 98% achieved “none or mild wrinkle severity” at week 4 per investigator assessment, the company said.
The median duration of treatment effect was 6 months, with some patients maintaining treatment results at 9 months, compared with a 3- to 4-month duration of treatment effect with conventional neuromodulators.
“Compelling data from the largest phase 3 clinical program ever conducted for glabellar lines demonstrated that Daxxify was well tolerated and achieved clinically significant improvement with long-lasting results and high patient satisfaction,” SAKURA investigator Jeffrey Dover, MD, co-director of SkinCare Physicians, Chestnut Hill, Mass., said in the news release.
“Notably,” said Dr. Dover, “Daxxify was able to demonstrate a long duration of effect while only utilizing 0.18 ng of core active ingredient in the 40-unit labeled indication for glabellar lines.”
Daxxify has a safety profile in line with other currently available neuromodulators in the aesthetics market, the company said, with no serious treatment-related adverse events reported in clinical trial participants.
The most common treatment-related adverse events in the pivotal studies were headache (6%), eyelid ptosis (2%) and facial paresis, including facial asymmetry (1%).
Daxxify is contraindicated in adults with hypersensitivity to any botulinum toxin preparation or any of the components in the formulation and infection at the injection sites.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The U.S. .
According to a company news release, Daxxify, an acetylcholine release inhibitor and neuromuscular blocking agent, is the first peptide-formulated, long-acting neuromodulator approved for this indication.
The approval of Daxxify, manufactured by Revance Therapeutics, was based on the data from the SAKURA phase 3 clinical trial program, which included more than 2,700 adults who received roughly 4,200 treatments, according to the company.
About three-quarters of participants achieved at least a two-grade improvement in glabellar lines at week 4 as judged by both investigator and patient, and 98% achieved “none or mild wrinkle severity” at week 4 per investigator assessment, the company said.
The median duration of treatment effect was 6 months, with some patients maintaining treatment results at 9 months, compared with a 3- to 4-month duration of treatment effect with conventional neuromodulators.
“Compelling data from the largest phase 3 clinical program ever conducted for glabellar lines demonstrated that Daxxify was well tolerated and achieved clinically significant improvement with long-lasting results and high patient satisfaction,” SAKURA investigator Jeffrey Dover, MD, co-director of SkinCare Physicians, Chestnut Hill, Mass., said in the news release.
“Notably,” said Dr. Dover, “Daxxify was able to demonstrate a long duration of effect while only utilizing 0.18 ng of core active ingredient in the 40-unit labeled indication for glabellar lines.”
Daxxify has a safety profile in line with other currently available neuromodulators in the aesthetics market, the company said, with no serious treatment-related adverse events reported in clinical trial participants.
The most common treatment-related adverse events in the pivotal studies were headache (6%), eyelid ptosis (2%) and facial paresis, including facial asymmetry (1%).
Daxxify is contraindicated in adults with hypersensitivity to any botulinum toxin preparation or any of the components in the formulation and infection at the injection sites.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
The U.S. .
According to a company news release, Daxxify, an acetylcholine release inhibitor and neuromuscular blocking agent, is the first peptide-formulated, long-acting neuromodulator approved for this indication.
The approval of Daxxify, manufactured by Revance Therapeutics, was based on the data from the SAKURA phase 3 clinical trial program, which included more than 2,700 adults who received roughly 4,200 treatments, according to the company.
About three-quarters of participants achieved at least a two-grade improvement in glabellar lines at week 4 as judged by both investigator and patient, and 98% achieved “none or mild wrinkle severity” at week 4 per investigator assessment, the company said.
The median duration of treatment effect was 6 months, with some patients maintaining treatment results at 9 months, compared with a 3- to 4-month duration of treatment effect with conventional neuromodulators.
“Compelling data from the largest phase 3 clinical program ever conducted for glabellar lines demonstrated that Daxxify was well tolerated and achieved clinically significant improvement with long-lasting results and high patient satisfaction,” SAKURA investigator Jeffrey Dover, MD, co-director of SkinCare Physicians, Chestnut Hill, Mass., said in the news release.
“Notably,” said Dr. Dover, “Daxxify was able to demonstrate a long duration of effect while only utilizing 0.18 ng of core active ingredient in the 40-unit labeled indication for glabellar lines.”
Daxxify has a safety profile in line with other currently available neuromodulators in the aesthetics market, the company said, with no serious treatment-related adverse events reported in clinical trial participants.
The most common treatment-related adverse events in the pivotal studies were headache (6%), eyelid ptosis (2%) and facial paresis, including facial asymmetry (1%).
Daxxify is contraindicated in adults with hypersensitivity to any botulinum toxin preparation or any of the components in the formulation and infection at the injection sites.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
Acute myocarditis a possible complication of monkeypox
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.