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Intimate partner violence and PTSD increase menopausal symptom risk
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
An estimated 33% of women in the United States have been sexually assaulted, and an estimated 25% have experienced IPV, so be aware of how common this “wicked problem” is, the way it impacts health, and what role you can play in educating and helping patients by connecting them to available resources.
But that is not enough. Consider measures such as training yourself and staff in how to assess for IPV and sexual assault and use of EHR to integrate IPV assessment into routine clinical care, as well as developing protocols to be followed when a patient discloses IPV or sexual assault. A multidisciplinary approach also can help, including victim service advocates and behavioral health clinicians to provide care and support.
State requirements for reporting partner and sexual violence differ, so be aware of your state laws.
A strength of this study is that it included emotional as well as physical IPV, which often is left out although it has serious impacts.
Rebecca C. Thurston, PhD, is from the department of psychiatry at the University of Pittsburgh, and Elizabeth Miller, MD, PhD, is from the division of adolescent and young adult medicine at the UPMC Children’s Hospital of Pittsburgh. These comments were taken from an accompanying editorial (JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5242). Dr. Thurston declared research support from the National Institutes of Health and consultancies for Pfizer, Procter & Gamble, and MAS Innovations.
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.
Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.
Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.
Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.
Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.
Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.
“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.
The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.
“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.
Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.
The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Intimate partner violence increases the risk of menopausal symptoms.
Major finding:
Study details: A cohort study in 2,016 women aged 40 years and older.
Disclosures: The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.
Source: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi:10.1001/jamainternmed.2018.5233.
Oral immunotherapy desensitizes youth with peanut allergy
Peanut-allergic children and adolescents treated with a peanut-derived oral immunotherapy drug have shown significant improvements in response to a challenge dose of peanut protein, according to data presented at the annual meeting of the American College of Allergy, Asthma, and Immunology.
A phase 3 placebo-controlled study, published simultaneously Nov. 18 in the New England Journal of Medicine, randomized 551 individuals with peanut allergy to receive an escalating dose of AR101 – an investigational peanut-derived biologic oral immunotherapy drug – ranging from 0.5-300 mg daily, or placebo.
After 12 months, 67.2% of the 372 participants aged 4-17 years who received the immunotherapy drug were able to eat a dose of 600 mg or more of peanut protein with only mild symptoms, compared with 4% of the 124 participants aged 4-17 years in the placebo group.
The secondary endpoints were whether participants could tolerate either a 300 mg or 1,000 mg dose in the exit food challenge. For the 300 mg dose, 76.6% of the immunotherapy group and 8.1% of the placebo group were able to tolerate it, and for the 1,000 mg group, 50.3% of the immunotherapy group were able to tolerate it, compared with 2.4% of the placebo group.
During the exit food challenge, the severity of symptoms was significantly higher in the placebo group than in the treatment group. One-quarter of participants in the treatment group had at most moderate symptoms, compared with 59% in the placebo group. However, severe symptoms were experienced by 11% of the placebo group, compared with 5% of the treatment group.
One in 10 participants in the active group had to be treated with rescue epinephrine during the exit food challenge, compared with 53% of participants in the placebo group, and the number who required a second dose of rescue epinephrine was 1% and 15%, respectively.
“These data show that, in the context of a clinical trial, among participants 4-17 years of age, AR101 had immunomodulatory activity, raised the threshold dose of peanut exposure triggering the onset of clinically significant allergic symptoms (among participants having symptoms), during the double-blind, placebo-controlled exit food challenge, and attenuated the severity of those symptoms when they occurred,” wrote Brian P. Vickery, MD, of Emory University in Atlanta, and his coauthors.
The 55 participants aged 18-55 years were analyzed separately, and researchers found that for the 600 mg exit food test, the difference between the two groups did not reach statistical significance.
Apart from adverse events that occurred during the exit food challenge, the rate of adverse events was slightly higher in the treatment group compared to the placebo group (98.7% vs. 95.2%). The most common adverse events in the treatment arm were abdominal pain, vomiting, oral pruritis, and nausea.
The study was funded by Aimmune Therapeutics. Three authors were employees of or investigators for Aimmune Therapeutics and one also had a patent pending for oral immunotherapy for peanut allergy. Most authors declared funding, grants, consultancies, or other support from the pharmaceutical industry, including from some from Aimmune.
SOURCE: Vickery BP et al. N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMoa1812856.
Over the past decade, more case reports and small studies have suggested that the use of tiny and incrementally increasing amount of peanut could desensitize those who are allergic to peanuts. This study, which uses a product based on defatted peanut flour, has shown that by the end of the course of treatment, two-thirds of those treated could consume around four peanuts.
However, the treatment was associated with side effects, many participants needed treatment with epinephrine, and the study has not yet addressed concerns about the longer term side effects of sustained allergen consumption, such as eosinophilic esophagitis.
The question also still remains as to whether the allergen tolerance is long-lasting or whether it will need to be maintained with regular exposure.
Michael R. Perkin, PhD, is affiliated with the Population Health Research Unit at St George’s, University of London. These comments are taken from an accompanying editorial (N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMe1813314). No conflicts of interest were declared.
Over the past decade, more case reports and small studies have suggested that the use of tiny and incrementally increasing amount of peanut could desensitize those who are allergic to peanuts. This study, which uses a product based on defatted peanut flour, has shown that by the end of the course of treatment, two-thirds of those treated could consume around four peanuts.
However, the treatment was associated with side effects, many participants needed treatment with epinephrine, and the study has not yet addressed concerns about the longer term side effects of sustained allergen consumption, such as eosinophilic esophagitis.
The question also still remains as to whether the allergen tolerance is long-lasting or whether it will need to be maintained with regular exposure.
Michael R. Perkin, PhD, is affiliated with the Population Health Research Unit at St George’s, University of London. These comments are taken from an accompanying editorial (N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMe1813314). No conflicts of interest were declared.
Over the past decade, more case reports and small studies have suggested that the use of tiny and incrementally increasing amount of peanut could desensitize those who are allergic to peanuts. This study, which uses a product based on defatted peanut flour, has shown that by the end of the course of treatment, two-thirds of those treated could consume around four peanuts.
However, the treatment was associated with side effects, many participants needed treatment with epinephrine, and the study has not yet addressed concerns about the longer term side effects of sustained allergen consumption, such as eosinophilic esophagitis.
The question also still remains as to whether the allergen tolerance is long-lasting or whether it will need to be maintained with regular exposure.
Michael R. Perkin, PhD, is affiliated with the Population Health Research Unit at St George’s, University of London. These comments are taken from an accompanying editorial (N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMe1813314). No conflicts of interest were declared.
Peanut-allergic children and adolescents treated with a peanut-derived oral immunotherapy drug have shown significant improvements in response to a challenge dose of peanut protein, according to data presented at the annual meeting of the American College of Allergy, Asthma, and Immunology.
A phase 3 placebo-controlled study, published simultaneously Nov. 18 in the New England Journal of Medicine, randomized 551 individuals with peanut allergy to receive an escalating dose of AR101 – an investigational peanut-derived biologic oral immunotherapy drug – ranging from 0.5-300 mg daily, or placebo.
After 12 months, 67.2% of the 372 participants aged 4-17 years who received the immunotherapy drug were able to eat a dose of 600 mg or more of peanut protein with only mild symptoms, compared with 4% of the 124 participants aged 4-17 years in the placebo group.
The secondary endpoints were whether participants could tolerate either a 300 mg or 1,000 mg dose in the exit food challenge. For the 300 mg dose, 76.6% of the immunotherapy group and 8.1% of the placebo group were able to tolerate it, and for the 1,000 mg group, 50.3% of the immunotherapy group were able to tolerate it, compared with 2.4% of the placebo group.
During the exit food challenge, the severity of symptoms was significantly higher in the placebo group than in the treatment group. One-quarter of participants in the treatment group had at most moderate symptoms, compared with 59% in the placebo group. However, severe symptoms were experienced by 11% of the placebo group, compared with 5% of the treatment group.
One in 10 participants in the active group had to be treated with rescue epinephrine during the exit food challenge, compared with 53% of participants in the placebo group, and the number who required a second dose of rescue epinephrine was 1% and 15%, respectively.
“These data show that, in the context of a clinical trial, among participants 4-17 years of age, AR101 had immunomodulatory activity, raised the threshold dose of peanut exposure triggering the onset of clinically significant allergic symptoms (among participants having symptoms), during the double-blind, placebo-controlled exit food challenge, and attenuated the severity of those symptoms when they occurred,” wrote Brian P. Vickery, MD, of Emory University in Atlanta, and his coauthors.
The 55 participants aged 18-55 years were analyzed separately, and researchers found that for the 600 mg exit food test, the difference between the two groups did not reach statistical significance.
Apart from adverse events that occurred during the exit food challenge, the rate of adverse events was slightly higher in the treatment group compared to the placebo group (98.7% vs. 95.2%). The most common adverse events in the treatment arm were abdominal pain, vomiting, oral pruritis, and nausea.
The study was funded by Aimmune Therapeutics. Three authors were employees of or investigators for Aimmune Therapeutics and one also had a patent pending for oral immunotherapy for peanut allergy. Most authors declared funding, grants, consultancies, or other support from the pharmaceutical industry, including from some from Aimmune.
SOURCE: Vickery BP et al. N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMoa1812856.
Peanut-allergic children and adolescents treated with a peanut-derived oral immunotherapy drug have shown significant improvements in response to a challenge dose of peanut protein, according to data presented at the annual meeting of the American College of Allergy, Asthma, and Immunology.
A phase 3 placebo-controlled study, published simultaneously Nov. 18 in the New England Journal of Medicine, randomized 551 individuals with peanut allergy to receive an escalating dose of AR101 – an investigational peanut-derived biologic oral immunotherapy drug – ranging from 0.5-300 mg daily, or placebo.
After 12 months, 67.2% of the 372 participants aged 4-17 years who received the immunotherapy drug were able to eat a dose of 600 mg or more of peanut protein with only mild symptoms, compared with 4% of the 124 participants aged 4-17 years in the placebo group.
The secondary endpoints were whether participants could tolerate either a 300 mg or 1,000 mg dose in the exit food challenge. For the 300 mg dose, 76.6% of the immunotherapy group and 8.1% of the placebo group were able to tolerate it, and for the 1,000 mg group, 50.3% of the immunotherapy group were able to tolerate it, compared with 2.4% of the placebo group.
During the exit food challenge, the severity of symptoms was significantly higher in the placebo group than in the treatment group. One-quarter of participants in the treatment group had at most moderate symptoms, compared with 59% in the placebo group. However, severe symptoms were experienced by 11% of the placebo group, compared with 5% of the treatment group.
One in 10 participants in the active group had to be treated with rescue epinephrine during the exit food challenge, compared with 53% of participants in the placebo group, and the number who required a second dose of rescue epinephrine was 1% and 15%, respectively.
“These data show that, in the context of a clinical trial, among participants 4-17 years of age, AR101 had immunomodulatory activity, raised the threshold dose of peanut exposure triggering the onset of clinically significant allergic symptoms (among participants having symptoms), during the double-blind, placebo-controlled exit food challenge, and attenuated the severity of those symptoms when they occurred,” wrote Brian P. Vickery, MD, of Emory University in Atlanta, and his coauthors.
The 55 participants aged 18-55 years were analyzed separately, and researchers found that for the 600 mg exit food test, the difference between the two groups did not reach statistical significance.
Apart from adverse events that occurred during the exit food challenge, the rate of adverse events was slightly higher in the treatment group compared to the placebo group (98.7% vs. 95.2%). The most common adverse events in the treatment arm were abdominal pain, vomiting, oral pruritis, and nausea.
The study was funded by Aimmune Therapeutics. Three authors were employees of or investigators for Aimmune Therapeutics and one also had a patent pending for oral immunotherapy for peanut allergy. Most authors declared funding, grants, consultancies, or other support from the pharmaceutical industry, including from some from Aimmune.
SOURCE: Vickery BP et al. N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMoa1812856.
FROM ACAAI 2018
Key clinical point: Oral peanut immunotherapy can improve tolerance in patients aged 4-17 with peanut allergy.
Major finding: Among patients treated with oral peanut immunotherapy, 67.2% were able to tolerate 600 mg of peanut protein, compared with 4% of the placebo group.
Study details: A randomized, placebo-controlled phase 3 study in 551 individuals with peanut allergy.
Disclosures: The study was funded by Aimmune Therapeutics. Three authors were employees of or investigators for Aimmune Therapeutics, and one also had a patent pending for oral immunotherapy for peanut allergy. Most authors declared funding, grants, consultancies, or other support from the pharmaceutical industry, including from some from Aimmune.
Source: Vickery BP et al. N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMoa1812856.
Increased risk of atrial fibrillation with migraine aura
The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.
Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.
After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.
In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.
“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”
The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.
The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.
“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”
In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.
Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.
The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).
The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.
However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.
The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.
SOURCE: Sen S et al. Neurology. 2018;91:1-9.
This article was updated 12/12/18.
The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.
Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.
After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.
In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.
“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”
The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.
The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.
“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”
In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.
Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.
The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).
The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.
However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.
The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.
SOURCE: Sen S et al. Neurology. 2018;91:1-9.
This article was updated 12/12/18.
The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.
Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.
After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.
In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.
“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”
The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.
The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.
“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”
In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.
Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.
The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).
The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.
However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.
The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.
SOURCE: Sen S et al. Neurology. 2018;91:1-9.
This article was updated 12/12/18.
FROM NEUROLOGY
Key clinical point: Aura in migraine is associated with an increased risk of atrial fibrillation.
Major finding: Individuals who experience migraine with aura have a 39% higher risk of atrial fibrillation than do those without aura or without migraine.
Study details: The longitudinal, community-based Atherosclerosis Risk in Communities Study in 11,939 individuals.
Disclosures: The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.
Source: Sen S et al. Neurology. 2018;91:1-9.
Lower glucose targets show improved mortality in cardiac patients
Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.
Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.
The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).
Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.
Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).
The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.
“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.
But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.
“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.
Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.
The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.
The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.
They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.
“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”
No conflicts of interest were declared.
After the multicenter NICE-SUGAR trial showed higher 90-day mortality in patients treated with intensive insulin therapy to lower blood glucose targets, compared with more moderate targets, enthusiasm has waned for tighter blood glucose control, James S. Krinsley, MD, argued in an editorial accompanying the study (CHEST 2018; 154[5]:1004-5). But the assumption of a “one-size-fits-all” approach to glucose control in the critically ill is a potential flaw of randomized clinical trials, he noted, and some patients may be better suited to tighter control than others. This study has shown that standardized protocols, including frequent measurement of blood glucose, can safely achieve tight blood glucose control in the ICU with low rates of hypoglycemia. If these findings are confirmed in larger multicenter clinical trials, it should prompt a rethink of blood glucose targets in the critically ill, he concluded.
Dr. Krinsley is director of critical care at Stamford (Conn.) Hospital and clinical professor of medicine at the Columbia University College of Physicians and Surgeons, New York. He declared consultancies or advisory board positions with Edwards Life Sciences, Medtronic, OptiScan Biomedical, and Roche Diagnostics.
After the multicenter NICE-SUGAR trial showed higher 90-day mortality in patients treated with intensive insulin therapy to lower blood glucose targets, compared with more moderate targets, enthusiasm has waned for tighter blood glucose control, James S. Krinsley, MD, argued in an editorial accompanying the study (CHEST 2018; 154[5]:1004-5). But the assumption of a “one-size-fits-all” approach to glucose control in the critically ill is a potential flaw of randomized clinical trials, he noted, and some patients may be better suited to tighter control than others. This study has shown that standardized protocols, including frequent measurement of blood glucose, can safely achieve tight blood glucose control in the ICU with low rates of hypoglycemia. If these findings are confirmed in larger multicenter clinical trials, it should prompt a rethink of blood glucose targets in the critically ill, he concluded.
Dr. Krinsley is director of critical care at Stamford (Conn.) Hospital and clinical professor of medicine at the Columbia University College of Physicians and Surgeons, New York. He declared consultancies or advisory board positions with Edwards Life Sciences, Medtronic, OptiScan Biomedical, and Roche Diagnostics.
After the multicenter NICE-SUGAR trial showed higher 90-day mortality in patients treated with intensive insulin therapy to lower blood glucose targets, compared with more moderate targets, enthusiasm has waned for tighter blood glucose control, James S. Krinsley, MD, argued in an editorial accompanying the study (CHEST 2018; 154[5]:1004-5). But the assumption of a “one-size-fits-all” approach to glucose control in the critically ill is a potential flaw of randomized clinical trials, he noted, and some patients may be better suited to tighter control than others. This study has shown that standardized protocols, including frequent measurement of blood glucose, can safely achieve tight blood glucose control in the ICU with low rates of hypoglycemia. If these findings are confirmed in larger multicenter clinical trials, it should prompt a rethink of blood glucose targets in the critically ill, he concluded.
Dr. Krinsley is director of critical care at Stamford (Conn.) Hospital and clinical professor of medicine at the Columbia University College of Physicians and Surgeons, New York. He declared consultancies or advisory board positions with Edwards Life Sciences, Medtronic, OptiScan Biomedical, and Roche Diagnostics.
Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.
Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.
The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).
Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.
Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).
The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.
“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.
But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.
“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.
Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.
The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.
The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.
They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.
“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”
No conflicts of interest were declared.
Tighter glucose control while minimizing the risk of severe hypoglycemia is associated with lower mortality among critically ill cardiac patents, new research suggests.
Researchers reported in CHEST on the outcomes of a multicenter retrospective cohort study in 1,809 adults in cardiac ICUs. Patients were treated either to a blood glucose target of 80-110 mg/dL or 90-140 mg/dL, based on the clinician’s preference, but using a computerized ICU insulin infusion protocol that the authors said had resulted in low rates of severe hypoglycemia.
The study found patients treated to the 80-110 mg/dL blood glucose target had a significantly lower unadjusted 30-day mortality compared to patients treated to the 90-140 mg/dL target (4.3% vs. 9.2%; P less than .001). The lower mortality in the lower target group was evident among both diabetic (4.7% vs. 12.9%; P less than .001) and nondiabetic patients (4.1% vs. 7.4%; P = .02).
Researchers also saw that unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose of 70-110 mg/dL, 8.3% mortality in those with blood glucose levels of 141-180 mg/dL, and 25% in those with a blood glucose level higher than 180 mg/dL.
Patients treated to the 80-110 mg/dL blood glucose target were more likely to experience an episode of moderate hypoglycemia, compared with those in the higher target group (18.6% vs. 8.3%; P less than .001). However, the rates of severe hypoglycemia were low in both groups, and the difference between the low and high target groups did not reach statistical significance (1.16% vs. 0.35%; P = .051).
The authors did note that patients whose blood glucose dropped below 60 mg/dL showed increased mortality, regardless of what target they was set for them. The 30-day unadjusted mortality in these patients was 15%, compared with 5.2% for patients in either group who did not experience a blood glucose level below 60 mg/dL.
“Our results further the discussion about the appropriate BG [blood glucose] target in the critically ill because they suggest that the BG target and severe hypoglycemia effects can be separated,” wrote Andrew M. Hersh, MD, of the division of pulmonary and critical care at San Antonio Military Medical Center, and his coauthors.
But they said the large differences in mortality seen between the two treatment targets should be interpreted with caution, as it was difficult to attribute that difference solely to an 18 mg/dL difference in blood glucose treatment targets.
“While we attempted to capture factors that influenced clinician choice, and while our model successfully achieved balance, suggesting that residual confounding was minimized, we suspect that some of the mortality signal may be attributable to residual confounding,” they wrote.
Another explanation could be that hypoglycemia was an ‘epiphenomenon’ of multiorgan failure, as some studies have found that both spontaneous and iatrogenic hypoglycemia were independently associated with mortality. “However, given the very-low rates of severe hypoglycemia found in both groups it is unlikely that this was a main driver of the mortality difference found,” the investigators wrote.
The majority of patients in the study had been admitted to the hospital for chest pain or acute coronary syndrome (43.3%), while 31.9% were admitted for cardiothoracic surgery, 6.8% for heart failure including cardiogenic shock, and 6% for vascular surgery.
The authors commented that a safe and reliable protocol for intensive insulin therapy, with high clinician compliance, could be the key to realizing its benefits, and could be aided by recent advances such as closed-loop insulin delivery systems.
They also stressed that their results did not support a rejection of current guidelines and instead called for large randomized, clinical trials to find a balance between benefits and harms of intensive insulin therapy.
“Instead our analysis suggests that trials such as NICE-SUGAR, and the conclusion they drew, may have been accurate only in the setting of technologies, which led to high rates of severe hypoglycemia.”
No conflicts of interest were declared.
FROM CHEST
Key clinical point: Tighter blood glucose control may reduce 30-day mortality in critically ill cardiac patients.
Major finding: Unadjusted 30-day mortality increased with increasing median glucose levels; 5.5% in patients with a blood glucose between 70 and 110 mg/dL, and 25% in those above 180 mg/dL.
Study details: A retrospective cohort study in 1,809 adults in cardiac intensive care units.
Disclosures: No conflicts of interest were declared.
Source: Hersh AM et al. Chest. 2018 Nov;154(5):1044-51.
Circulating tumor DNA identified by fragment size
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Cell-free DNA analysis has tremendous diagnostic potential and so is a very active area of research. In this study, researchers were able to identify five variables and develop models for the detection of cancer following analysis of circulating tumor DNA. One of these models based on DNA fragmentation pattern performed very well, and so fragment length analyses could develop into a general test for the presence of cancer.
However confirmation of these findings in large, multicenter clinical trials is still needed. There is also the problem that size selection can result in a loss of circulating tumor DNA for analysis or may introduce biases. We also need to understand the mechanisms underpinning the different fragment size patterns seen in the study. But this study still substantially extends the potential of cell-free, DNA-based diagnostic tests.
Ellen Heitzer, PhD, and Michael R. Speicher, MD, are from the Medical University of Graz (Austria). These comments are taken from an accompanying editorial (Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aav3873). Both authors declared research funding from Servier and Dr. Heitzer declared laboratory research funding from Freenome and PreAnalytiX.
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Circulating tumor DNA could be effectively isolated from plasma by focusing on a particular range of fragment sizes, which paves the way for noninvasive genomic analysis of tumor DNA, new research suggests.
In a study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls, DNA fragment length could be used to distinguish circulating tumor DNA (ctDNA) from other cell-free DNA (cfDNA), investigators reported in Science Translational Medicine.
“We hypothesized that we could improve the sensitivity for noninvasive cancer genomics by selective sequencing of ctDNA fragments and by leveraging differences in the biology that determine DNA fragmentation,” wrote Florent Mouliere, PhD, from the Cancer Research UK Cambridge Institute, and coauthors.
Cell-free plasma fragments are often cleaved at around 167 base pairs in length and differences in length between circulating fetal and maternal DNA are already used for noninvasive prenatal diagnosis. However, the authors said that only a few studies, with conflicting results, have looked at the size distribution of tumor-derived cfDNA.
The study used two approaches to determining the size profile of mutant ctDNA. The first looked at tumor and nontumor cfDNA in mice with human ovarian cancer xenografts and the second approach used deep sequencing in 19 cancer patients. This revealed that tumor-derived cfDNA was most commonly found in fragments between 90-150 base pairs or 250-320 base pairs in size.
The researchers also noted that mutant circulating tumor DNA was generally more fragmented than nonmutant cfDNA and that patients with untreated advanced cancer showed consistently shorter lengths of mutant DNA.
The next question was whether size selection and other biological properties – such as somatic alterations – of the cfDNA could be used to enhance detection of ctDNA via machine learning technology.
Two models, designed to distinguish between healthy and cancerous samples, were developed using 153 samples, then validated on two datasets of 94 and 83 samples.
One of these models correctly classified cancerous samples in 94% of samples from patients with cancers known to have high levels of ctDNA – colorectal, cholangiocarcinoma, ovarian, breast, and melanoma – and in 65% of samples from low-ctDNA cancers – pancreatic, renal, and glioma.
Another model focused just on fragmentation patterns and was still able to distinguish cancer samples from those of healthy controls, although with slightly reduced area under the curve.
“Our results indicate that exploiting fundamental properties of cfDNA with fragment-specific analyses can allow more sensitive evaluation of ctDNA,” the authors wrote. “We identified features that could determine the presence and amount of ctDNA in plasma samples, without a prior knowledge of somatic aberrations.”
The authors pointed out that size selection of DNA fragments was relatively simple and cheap, and was also compatible with other genome-wide and targeted genomic analyses, “greatly increasing the potential value and utility of liquid biopsies as well as the cost-effectiveness of cfDNA sequencing.”
However, they cautioned that their catalogue had focused solely on double-stranded DNA and was subject to potential biases from the DNA extraction and sequencing methods they used in the study. They also commented that other biological effects could help refine the analysis of ctDNA.
“Other bodily fluids [urine, cerebrospinal fluid, and saliva], different nucleic acids and structures, altered mechanisms of release into circulation, or sample processing methods could exhibit varying fragment size signatures and could offer additional exploitable biological patterns for selective sequencing,” they wrote.
The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in ctDNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
SOURCE: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: The size of cell-free DNA could be used to single out circulating tumor DNA.
Major finding: Circulating tumor DNA fragments are more commonly found in the 90-150 base pair range.
Study details: A study of 344 plasma samples from 200 patients with 18 cancer types and 65 samples from healthy controls.
Disclosures: The study was supported by the University of Cambridge, Cancer Research UK, and the Engineering and Physical Sciences Research Council. Research supporting the study was also funded by the European Research Council, the National Institute for Health Research Cambridge, National Cancer Research Network, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa, Target Ovarian Cancer, the Medical Research Council, and AstraZeneca. Three authors are cofounders, shareholders, and officers/consultants in a company specializing in circulating tumor DNA analysis. One author declared research funding and advisory board fees from private industry. Seven authors are listed on related patents.
Source: Mouliere F et al. Sci Transl Med. 2018 Nov 7. doi: 10.1126/scitranslmed.aat4921.
Exercise improves outcomes for patients with heart failure and OSA
Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].
Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.
The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.
The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.
All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.
Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.
“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”
A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.
The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.
All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.
“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”
Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.
The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.
“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”
However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.
No conflicts of interest were declared.
SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext
Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].
Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.
The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.
The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.
All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.
Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.
“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”
A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.
The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.
All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.
“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”
Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.
The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.
“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”
However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.
No conflicts of interest were declared.
SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext
Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].
Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.
The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.
The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.
All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.
Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.
“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”
A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.
The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.
All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.
“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”
Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.
The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.
“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”
However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.
No conflicts of interest were declared.
SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext
FROM CHEST
Key clinical point: Exercise alone or with CPAP achieves additional improvements to quality of life in patients with heart failure and obstructive sleep apnea.
Major finding: Individuals with heart failure and obstructive sleep apnea showed significant improvements to quality of life with exercise.
Study details: Randomized controlled trial in 65 patients with heart failure and obstructive sleep apnea.
Disclosures: The study was supported by the Associacao Fundo de Incentivo a Pesquisa, Sao Paulo Research Foundation. No conflicts of interest were declared.
Source: Servantes D et al.Chest 2018;154:808-817.doi:10.1016/j.chest.2018.05.011
Platelet transfusion threshold matters for preterm infants
A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.
A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).
Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.
The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.
The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.
“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.
However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.
“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”
The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.
SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.
A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.
A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).
Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.
The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.
The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.
“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.
However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.
“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”
The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.
SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.
A lower threshold for platelet transfusions in preterm infants with severe thrombocytopenia is associated with significantly lower incidence of death and major bleeding, compared with a higher threshold, a new study suggests.
A new major bleeding episode or death occurred in 26% of infants in the high-threshold group, compared with 19% in the low-threshold group, representing a 57% higher risk of poor outcomes even after researchers adjusted for gestational age and intrauterine growth restriction (odds ratio, 1.57; P = .02).
Researchers reported the results of a trial in 660 infants with a mean gestational age of 26.6 weeks, who were randomized to a platelet infusion either at a high platelet–count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
“Although retrospective studies have suggested that platelet transfusions may cause harm in neonates independently of the disease process, data from randomized controlled trials to support this are lacking,” Anna Curley, MD, of the National Maternity Hospital in Dublin and her coauthors reported in the New England Journal of Medicine.
The rates of minor or worse bleeding were similar between the two groups, and the percentage of infants surviving with bronchopulmonary dysplasia at 36 weeks of corrected age was higher in the high-threshold group (63% vs. 54%; OR, 1.54).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups.
The outcomes of transfusions were not influenced by other factors such as intrauterine growth restriction, gestational age, or postnatal age at randomization.
“Our trial highlights the importance of trials of platelet transfusion involving patients with conditions other than haematological malignancies,” the authors wrote.
However they acknowledged that the reasons for the differences in mortality and outcomes between the two study groups were unknown.
“Platelets have recognized immunological and inflammatory effects, outside of effects on hemostasis,” they wrote. “The effect of transfusing adult platelets to a delicately balance neonatal hemostatic system with relatively hypofunctional platelets is also poorly understood.”
The study was supported by the National Health Service Blood and Transplant Research and Development Committee and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.
SOURCE: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: The odds of new major bleeding or death were 57% higher in preterm infants who received a platelet transfusion at a higher threshold of 50,000 per mm3 than at a lower threshold of 25,000 mm3 (P = .02).Study details: Randomized study in 660 preterm infants with severe thrombocytopenia.
Disclosures: The study was supported by the National Health Service Blood and Transplant Research and Development Committee, and other foundations. Authors reported financial disclosures related to Sanquin and Cerus.
Source: Curley A et al. N Engl J Med. 2018 Nov 2. doi: 10.1056/NEJMoa1807320.
Lower threshold for platelet transfusions appears safer
A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.
Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm3 or 25,000/mm3.
The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.
Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.
The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.
When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).
The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).
The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm3 to 25,000/mm3 may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.
However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.
The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.
This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.
One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.
A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.
Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm3 or 25,000/mm3.
The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.
Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.
The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.
When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).
The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).
The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm3 to 25,000/mm3 may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.
However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.
The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.
This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.
One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.
A lower threshold for platelet transfusions may be safer for preterm infants with severe thrombocytopenia, a new study suggests.
Researchers randomized preterm infants with severe thrombocytopenia to receive transfusions at platelet count thresholds of 50,000/mm3 or 25,000/mm3.
The team found that patients in the high-threshold group had a significantly higher risk of major bleeding or death.
Anna Curley, MD, of the National Maternity Hospital in Dublin, Ireland, and her colleagues reported this finding in The New England Journal of Medicine.
The researchers studied 660 infants with a mean gestational age of 26.6 weeks. They were randomized to receive platelet transfusions at a high platelet-count threshold of 50,000/mm3 or a low threshold of 25,000/mm3.
Within 28 days of randomization, a new major bleeding episode or death occurred in 26% of the high-threshold group and 19% of the low-threshold group.
When the researchers adjusted for gestational age, intrauterine growth restriction, and trial site, the odds ratio (OR) for major bleeding or death was 1.57 (95% confidence interval [CI], 1.06-2.32; P=0.02).
The OR for death alone was 1.56 (95% CI, 0.95-2.55), and the hazard ratio for at least one major bleeding episode was 1.32 (95% CI, 1.00-1.74).
The rates of serious adverse events, not including major bleeding, were similar between the high- and low-threshold groups—25% and 22%, respectively (OR=1.14; 95% CI, 0.78-1.67).
The researchers said the results of this trial suggest that reducing the transfusion threshold from 50,000/mm3 to 25,000/mm3 may prevent death or major bleeding in 7 of 100 preterm neonates with severe thrombocytopenia.
However, the team also acknowledged that it isn’t clear why reducing the threshold may reduce the risk of mortality or major bleeding in this patient group.
The researchers said a range of factors might play a role in adverse outcomes of platelet transfusion in preterm neonates, including inflammatory consequences, hemodynamic shifts, fragility of the germinal matrix, disturbances in organ and brain blood flow, preterm lungs with a large capillary bed and abundant immune cells, platelet-derived reactive oxygen species, proangiogenic factors, and vessel occlusion by platelet microthrombi.
This study was supported by the National Health Service Blood and Transplant Research and Development Committee, Sanquin Research, Addenbrooke’s Charitable Trust, the Neonatal Breath of Life Fund, and the National Institute for Health Research Clinical Research Network.
One study author reported consulting for Sanquin Research, and another declared travel funds from Cerus Corporation.
Antipsychotic drugs failed to shorten ICU delirium
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Antipsychotics do not reduce the duration or incidence of delirium in intensive care.
Major finding: Patients treated with antipsychotics showed similar median days without delirium or coma, compared with those treated with placebo.
Study details: A randomized, double-blind, placebo-controlled trial in 566 intensive care patients.
Disclosures: The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors were supported by the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
Source: Girard TD et al. N Engl J Med. 2018 Oct 22. doi: 10.1056/NEJMoa1808217.
VTE risk after gynecologic surgery lower with laparoscopic procedures
according to a study published in Obstetrics & Gynecology.
The retrospective cohort study looked at data from 37,485 patients who underwent 43,751 gynecologic surgical procedures, including hysterectomy and myomectomy, at two tertiary care academic hospitals.
Overall, 96 patients (0.2%) were diagnosed with postoperative venous thromboembolism. However patients who underwent laparoscopic or vaginal surgery had a significant 78% and 93% lower risk of venous thromboembolism, respectively, than those who underwent laparotomy, even after adjusting for potential confounders such as age, cancer, race, pharmacologic thromboprophylaxis, and surgical time.
The incidence of postoperative thromboembolism was significantly higher among patients undergoing gynecologic surgery for cancer (1.1%). The incidence among those undergoing surgery for benign indications was only 0.2%, and the highest incidence was among patients with cancer who underwent laparotomy (2.2%).
“This study adds to data demonstrating that venous thromboembolism is rare in gynecologic surgery, particularly when a patient undergoes a minimally invasive procedure for benign indications,” wrote Dr. Elisa M. Jorgensen of Beth Israel Deaconess Medical Center, and her coauthors.
Among the 8,273 patients who underwent a hysterectomy, there were 55 cases of venous thromboembolism – representing an 0.7% incidence. However patients who underwent laparotomy had a 1% incidence of postoperative venous thromboembolism, while those who underwent laparoscopic hysterectomy had an 0.3% incidence and those who underwent vaginal hysterectomy had an 0.1% incidence.
Laparotomy was the most common mode of surgery for hysterectomy – accounting for 57% of operations – while 34% were laparoscopic and 9% were vaginal.
However, the authors noted that the use of laparoscopy increased and laparotomy declined over the 9 years of the study. In 2006, 12% of hysterectomies were laparoscopic, compared with 55% in 2015, while over that same period the percentage of laparotomies dropped from 74% to 41%, and the percentage of vaginal procedures declined from 14% to 4%.
“Because current practice guidelines do not account for mode of surgery, we find them to be insufficient for the modern gynecologic surgeon to counsel patients on their individual venous thromboembolism risk or to make ideal decisions regarding selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Only 5 patients of the 2,851 who underwent myomectomy developed postoperative VTE – an overall incidence of 0.2% – and the authors said numbers were too small to analyze. Vaginal or hysteroscopic myomectomy was the most common surgical method, accounting for 62% of procedures, compared with 23% for laparotomies and 15% for laparoscopies.
More than 90% of patients who experienced postoperative thromboembolism had received some form of thromboprophylaxis before surgery, either mechanical, pharmacologic, or both. In comparison, only 55% of the group who didn’t experience thromboembolism had received thromboprophylaxis.
“The high rate of prophylaxis among patients who developed postoperative venous thromboembolism may reflect surgeons’ abilities to preoperatively identify patients at increased risk, guiding appropriate selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Addressing the study’s limitations, the authors noted that they were not able to capture data on patients’ body mass index and also were unable to account for patients who might have been diagnosed and treated for postoperative VTE at other hospitals.
No conflicts of interest were declared.
SOURCE: Jorgensen EM et al. Obstet Gynecol. 2018 Nov;132:1275-84.
The aim of this study was to determine the 3-month postoperative incidence of venous thromboembolism among patients undergoing gynecologic surgery. The study also addressed the mode of surgery to allow a comparison between laparotomy and minimally invasive approaches.
Postoperative VTE was defined as deep venous thrombosis of the lower extremities, pulmonary embolism, or both that occurred within 90 days of surgery. A key component of the study was that clinically recognized VTEs that required treatment with anticoagulation, vena caval filter, or both were included.
The study evaluated 43,751 gynecological cases among 37,485 patients. As expected, 59% of the cases were classified as vaginal surgery, 24% were laparoscopic cases, and 17% of the cases were laparotomies.
Of the 8,273 hysterectomies, 57% were via an abdominal approach, 34% were laparoscopic, and 9 were vaginal cases.
Overall, 0.2% of patients were diagnosed with a VTE. As expected, the greatest incidence of VTE was in patients with cancer who underwent a laparotomy. Those with a VTE were significantly more likely to have had an inpatient stay (longer than 24 hours), a cancer diagnosis, a longer surgical time, and an American Society of Anesthesiologists score of 3 or more. They also were older (mean age 56 years vs. 44 years). Of note, 20% of the VTE group identified as black.
Among patients who had a hysterectomy, there were VTEs in 0.7%: 1% in the laparotomy group, 0.3% in the laparoscopic group, and only 0.1% in the vaginal hysterectomy group.
It is interesting to note that 91% of the patients diagnosed with a VTE did received preoperative VTE prophylaxis. The authors noted that the high rate of prophylaxis may have reflected the surgeon’s ability to identify patients who are at high risk.
The authors recognized that the current guidelines do not stratify VTE risk based on the mode of surgery. Further, they noted that low-risk patients undergoing low-risk surgery may be receiving pharmacologic VTE prophylaxis, thus placing these patients at risk for complications related to such therapy.
This paper by Jorgensen et al. should remind us that VTE prophylaxis should be individualized. Patients may not fit nicely into boxes on our EMR; each clinical decision should be made for each patient and for each clinical scenario. The surgeon’s responsibility is to adopt the evidence-based guidelines that serve each individual patient’s unique risk/benefit profile.
David M. Jaspan, DO, is director of minimally invasive and pelvic surgery and chairman of the department of obstetrics and gynecology at the Einstein Medical Center in Philadelphia. Dr. Jaspan, who was asked to comment on the Jorgenson et al. article, said he had no relevant financial disclosures.
The aim of this study was to determine the 3-month postoperative incidence of venous thromboembolism among patients undergoing gynecologic surgery. The study also addressed the mode of surgery to allow a comparison between laparotomy and minimally invasive approaches.
Postoperative VTE was defined as deep venous thrombosis of the lower extremities, pulmonary embolism, or both that occurred within 90 days of surgery. A key component of the study was that clinically recognized VTEs that required treatment with anticoagulation, vena caval filter, or both were included.
The study evaluated 43,751 gynecological cases among 37,485 patients. As expected, 59% of the cases were classified as vaginal surgery, 24% were laparoscopic cases, and 17% of the cases were laparotomies.
Of the 8,273 hysterectomies, 57% were via an abdominal approach, 34% were laparoscopic, and 9 were vaginal cases.
Overall, 0.2% of patients were diagnosed with a VTE. As expected, the greatest incidence of VTE was in patients with cancer who underwent a laparotomy. Those with a VTE were significantly more likely to have had an inpatient stay (longer than 24 hours), a cancer diagnosis, a longer surgical time, and an American Society of Anesthesiologists score of 3 or more. They also were older (mean age 56 years vs. 44 years). Of note, 20% of the VTE group identified as black.
Among patients who had a hysterectomy, there were VTEs in 0.7%: 1% in the laparotomy group, 0.3% in the laparoscopic group, and only 0.1% in the vaginal hysterectomy group.
It is interesting to note that 91% of the patients diagnosed with a VTE did received preoperative VTE prophylaxis. The authors noted that the high rate of prophylaxis may have reflected the surgeon’s ability to identify patients who are at high risk.
The authors recognized that the current guidelines do not stratify VTE risk based on the mode of surgery. Further, they noted that low-risk patients undergoing low-risk surgery may be receiving pharmacologic VTE prophylaxis, thus placing these patients at risk for complications related to such therapy.
This paper by Jorgensen et al. should remind us that VTE prophylaxis should be individualized. Patients may not fit nicely into boxes on our EMR; each clinical decision should be made for each patient and for each clinical scenario. The surgeon’s responsibility is to adopt the evidence-based guidelines that serve each individual patient’s unique risk/benefit profile.
David M. Jaspan, DO, is director of minimally invasive and pelvic surgery and chairman of the department of obstetrics and gynecology at the Einstein Medical Center in Philadelphia. Dr. Jaspan, who was asked to comment on the Jorgenson et al. article, said he had no relevant financial disclosures.
The aim of this study was to determine the 3-month postoperative incidence of venous thromboembolism among patients undergoing gynecologic surgery. The study also addressed the mode of surgery to allow a comparison between laparotomy and minimally invasive approaches.
Postoperative VTE was defined as deep venous thrombosis of the lower extremities, pulmonary embolism, or both that occurred within 90 days of surgery. A key component of the study was that clinically recognized VTEs that required treatment with anticoagulation, vena caval filter, or both were included.
The study evaluated 43,751 gynecological cases among 37,485 patients. As expected, 59% of the cases were classified as vaginal surgery, 24% were laparoscopic cases, and 17% of the cases were laparotomies.
Of the 8,273 hysterectomies, 57% were via an abdominal approach, 34% were laparoscopic, and 9 were vaginal cases.
Overall, 0.2% of patients were diagnosed with a VTE. As expected, the greatest incidence of VTE was in patients with cancer who underwent a laparotomy. Those with a VTE were significantly more likely to have had an inpatient stay (longer than 24 hours), a cancer diagnosis, a longer surgical time, and an American Society of Anesthesiologists score of 3 or more. They also were older (mean age 56 years vs. 44 years). Of note, 20% of the VTE group identified as black.
Among patients who had a hysterectomy, there were VTEs in 0.7%: 1% in the laparotomy group, 0.3% in the laparoscopic group, and only 0.1% in the vaginal hysterectomy group.
It is interesting to note that 91% of the patients diagnosed with a VTE did received preoperative VTE prophylaxis. The authors noted that the high rate of prophylaxis may have reflected the surgeon’s ability to identify patients who are at high risk.
The authors recognized that the current guidelines do not stratify VTE risk based on the mode of surgery. Further, they noted that low-risk patients undergoing low-risk surgery may be receiving pharmacologic VTE prophylaxis, thus placing these patients at risk for complications related to such therapy.
This paper by Jorgensen et al. should remind us that VTE prophylaxis should be individualized. Patients may not fit nicely into boxes on our EMR; each clinical decision should be made for each patient and for each clinical scenario. The surgeon’s responsibility is to adopt the evidence-based guidelines that serve each individual patient’s unique risk/benefit profile.
David M. Jaspan, DO, is director of minimally invasive and pelvic surgery and chairman of the department of obstetrics and gynecology at the Einstein Medical Center in Philadelphia. Dr. Jaspan, who was asked to comment on the Jorgenson et al. article, said he had no relevant financial disclosures.
according to a study published in Obstetrics & Gynecology.
The retrospective cohort study looked at data from 37,485 patients who underwent 43,751 gynecologic surgical procedures, including hysterectomy and myomectomy, at two tertiary care academic hospitals.
Overall, 96 patients (0.2%) were diagnosed with postoperative venous thromboembolism. However patients who underwent laparoscopic or vaginal surgery had a significant 78% and 93% lower risk of venous thromboembolism, respectively, than those who underwent laparotomy, even after adjusting for potential confounders such as age, cancer, race, pharmacologic thromboprophylaxis, and surgical time.
The incidence of postoperative thromboembolism was significantly higher among patients undergoing gynecologic surgery for cancer (1.1%). The incidence among those undergoing surgery for benign indications was only 0.2%, and the highest incidence was among patients with cancer who underwent laparotomy (2.2%).
“This study adds to data demonstrating that venous thromboembolism is rare in gynecologic surgery, particularly when a patient undergoes a minimally invasive procedure for benign indications,” wrote Dr. Elisa M. Jorgensen of Beth Israel Deaconess Medical Center, and her coauthors.
Among the 8,273 patients who underwent a hysterectomy, there were 55 cases of venous thromboembolism – representing an 0.7% incidence. However patients who underwent laparotomy had a 1% incidence of postoperative venous thromboembolism, while those who underwent laparoscopic hysterectomy had an 0.3% incidence and those who underwent vaginal hysterectomy had an 0.1% incidence.
Laparotomy was the most common mode of surgery for hysterectomy – accounting for 57% of operations – while 34% were laparoscopic and 9% were vaginal.
However, the authors noted that the use of laparoscopy increased and laparotomy declined over the 9 years of the study. In 2006, 12% of hysterectomies were laparoscopic, compared with 55% in 2015, while over that same period the percentage of laparotomies dropped from 74% to 41%, and the percentage of vaginal procedures declined from 14% to 4%.
“Because current practice guidelines do not account for mode of surgery, we find them to be insufficient for the modern gynecologic surgeon to counsel patients on their individual venous thromboembolism risk or to make ideal decisions regarding selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Only 5 patients of the 2,851 who underwent myomectomy developed postoperative VTE – an overall incidence of 0.2% – and the authors said numbers were too small to analyze. Vaginal or hysteroscopic myomectomy was the most common surgical method, accounting for 62% of procedures, compared with 23% for laparotomies and 15% for laparoscopies.
More than 90% of patients who experienced postoperative thromboembolism had received some form of thromboprophylaxis before surgery, either mechanical, pharmacologic, or both. In comparison, only 55% of the group who didn’t experience thromboembolism had received thromboprophylaxis.
“The high rate of prophylaxis among patients who developed postoperative venous thromboembolism may reflect surgeons’ abilities to preoperatively identify patients at increased risk, guiding appropriate selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Addressing the study’s limitations, the authors noted that they were not able to capture data on patients’ body mass index and also were unable to account for patients who might have been diagnosed and treated for postoperative VTE at other hospitals.
No conflicts of interest were declared.
SOURCE: Jorgensen EM et al. Obstet Gynecol. 2018 Nov;132:1275-84.
according to a study published in Obstetrics & Gynecology.
The retrospective cohort study looked at data from 37,485 patients who underwent 43,751 gynecologic surgical procedures, including hysterectomy and myomectomy, at two tertiary care academic hospitals.
Overall, 96 patients (0.2%) were diagnosed with postoperative venous thromboembolism. However patients who underwent laparoscopic or vaginal surgery had a significant 78% and 93% lower risk of venous thromboembolism, respectively, than those who underwent laparotomy, even after adjusting for potential confounders such as age, cancer, race, pharmacologic thromboprophylaxis, and surgical time.
The incidence of postoperative thromboembolism was significantly higher among patients undergoing gynecologic surgery for cancer (1.1%). The incidence among those undergoing surgery for benign indications was only 0.2%, and the highest incidence was among patients with cancer who underwent laparotomy (2.2%).
“This study adds to data demonstrating that venous thromboembolism is rare in gynecologic surgery, particularly when a patient undergoes a minimally invasive procedure for benign indications,” wrote Dr. Elisa M. Jorgensen of Beth Israel Deaconess Medical Center, and her coauthors.
Among the 8,273 patients who underwent a hysterectomy, there were 55 cases of venous thromboembolism – representing an 0.7% incidence. However patients who underwent laparotomy had a 1% incidence of postoperative venous thromboembolism, while those who underwent laparoscopic hysterectomy had an 0.3% incidence and those who underwent vaginal hysterectomy had an 0.1% incidence.
Laparotomy was the most common mode of surgery for hysterectomy – accounting for 57% of operations – while 34% were laparoscopic and 9% were vaginal.
However, the authors noted that the use of laparoscopy increased and laparotomy declined over the 9 years of the study. In 2006, 12% of hysterectomies were laparoscopic, compared with 55% in 2015, while over that same period the percentage of laparotomies dropped from 74% to 41%, and the percentage of vaginal procedures declined from 14% to 4%.
“Because current practice guidelines do not account for mode of surgery, we find them to be insufficient for the modern gynecologic surgeon to counsel patients on their individual venous thromboembolism risk or to make ideal decisions regarding selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Only 5 patients of the 2,851 who underwent myomectomy developed postoperative VTE – an overall incidence of 0.2% – and the authors said numbers were too small to analyze. Vaginal or hysteroscopic myomectomy was the most common surgical method, accounting for 62% of procedures, compared with 23% for laparotomies and 15% for laparoscopies.
More than 90% of patients who experienced postoperative thromboembolism had received some form of thromboprophylaxis before surgery, either mechanical, pharmacologic, or both. In comparison, only 55% of the group who didn’t experience thromboembolism had received thromboprophylaxis.
“The high rate of prophylaxis among patients who developed postoperative venous thromboembolism may reflect surgeons’ abilities to preoperatively identify patients at increased risk, guiding appropriate selection of thromboprophylaxis,” Dr. Jorgenson and her associates wrote.
Addressing the study’s limitations, the authors noted that they were not able to capture data on patients’ body mass index and also were unable to account for patients who might have been diagnosed and treated for postoperative VTE at other hospitals.
No conflicts of interest were declared.
SOURCE: Jorgensen EM et al. Obstet Gynecol. 2018 Nov;132:1275-84.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point: Laparoscopic gynecologic surgery is associated with a lower risk of postoperative VTE than laparotomy.
Major finding: Laparoscopic hysterectomy was associated with a 78% lower incidence of postoperative VTE than laparotomy.
Study details: Retrospective cohort study of 37,485 patients who underwent 43,751 gynecologic surgical procedures
Disclosures: No conflicts of interest were declared.
Source: Jorgensen EM et al. Obstet Gynecol. 2018 Nov;132:1275-84.