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Is acetaminophen really safer than NSAIDs in heart disease?
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
New research calls into question the assumption that acetaminophen is safer than NSAIDs for patients with known cardiovascular disease (CVD) or CVD risk factors.
The analysis found a significant correlation between the use of acetaminophen and elevated systolic blood pressure.
While acetaminophen may still be safer than NSAIDs from a bleeding risk standpoint, or in patients with known kidney disease, “the gap may not be as large as once thought,” Rahul Gupta, MD, cardiologist with Lehigh Valley Health Network, Allentown, Pa., said in an interview.
“Cautious use is recommended over the long term, especially in patients with pre-existing hypertension or cardiovascular risk factors,” Dr. Gupta said.
The study was presented at the Hypertension Scientific Sessions, San Diego, sponsored by the American Heart Association.
Acetaminophen is one of the most widely used over-the-counter medications, as it is considered a safer medication for long-term use since it lacks the anti-inflammatory effects of NSAIDs, Dr. Gupta explained.
NSAIDs have been known to raise blood pressure, but the effect of acetaminophen in this regard has not been well studied. Observational studies have shown contradictory results in terms of its effect on blood pressure, he noted.
To investigate further, Dr. Gupta and colleagues did a meta-analysis of three studies that compared the effect of acetaminophen (3-4 g/day) versus placebo on systolic and diastolic ambulatory blood pressure in patients with heart disease or hypertension. Together, the studies included 172 adults (mean age, 60 years; 73% male).
They found that patients receiving acetaminophen had significantly higher systolic blood pressure, compared with those receiving placebo (standard mean difference [SMD] = 0.35; 95% confidence interval, 0.08-0.63; P = .01).
Subgroup analysis of the effect on hypertensive patients showed significant change in systolic blood pressure as well (SMD = 0.38; 95% CI, 0.05-0.71; P = .02).
“Interestingly, there was no significant difference in the effect on diastolic blood pressure,” Dr. Gupta commented.
Reached for comment, Timothy S. Anderson, MD, clinical investigator in the Division of General Medicine at Beth Israel Deaconess Medical Center and assistant professor of medicine at the Harvard Medical School, both in Boston, said this is “an interesting and not particularly well-known issue.”
“However, most of the trials look at very high doses of acetaminophen use (for example, six to eight of the 500 mg pills each day) so we don’t really know whether the more common patterns of using one to two acetaminophen pills every once in a while is problematic,” Dr. Anderson told this news organization.
“We also don’t have data showing a direct harm from these medications with regards to strokes or heart attacks or other downstream consequences of high blood pressure. Ideally we would need a head-to-head trial comparing ibuprofen-type medications to acetaminophen-type medications,” Dr. Anderson said.
The study had no specific funding. Dr. Gupta and Dr. Anderson reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2022
Continuous cuffless monitoring may fuel lifestyle change to lower BP
Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.
“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.
“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.
Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
Empowering data
The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.
After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.
Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.
Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.
Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.
Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.
On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.
Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.
Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.
“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.
He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”
“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.
He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.
Transforming technology
Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.
“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.
“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.
“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.
Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
Ready for prime time?
In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.
Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”
“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.
He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.
“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.
In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”
The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.
A version of this article first appeared on Medscape.com.
Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.
“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.
“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.
Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
Empowering data
The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.
After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.
Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.
Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.
Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.
Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.
On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.
Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.
Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.
“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.
He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”
“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.
He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.
Transforming technology
Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.
“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.
“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.
“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.
Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
Ready for prime time?
In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.
Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”
“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.
He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.
“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.
In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”
The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.
A version of this article first appeared on Medscape.com.
Wearing a cuffless device on the wrist to continuously monitor blood pressure was associated with a significantly lower systolic BP at 6 months among hypertensive adults, real-world results from Europe show.
“We don’t know what they did to reduce their blood pressure,” Jay Shah, MD, Division of Cardiology, Mayo Clinic Arizona, Phoenix, told this news organization.
“The idea is that because they were exposed to their data on a continual basis, that may have prompted them to do something that led to an improvement in their blood pressure, whether it be exercise more, go to their doctor, or change their medication,” said Dr. Shah, who is also chief medical officer for Aktiia.
Dr. Shah presented the study at the Hypertension Scientific Sessions, San Diego.
Empowering data
The study used the Aktiia 24/7 BP monitor; Atkiia funded the trial. The monitor passively and continually monitors BP values from photoplethysmography signals collected via optical sensors at the wrist.
After initial individualized calibration using a cuff-based reference, BP measurements are displayed on a smartphone app, allowing users to consistently monitor their own BP for long periods of time.
Aktiia received CE mark in Europe in January 2021 and is currently under review by the U.S. Food and Drug Administration.
Dr. Shah and colleagues analyzed systolic BP (SBP) trends among 838 real-world Aktiia users in Europe (age 57 ± 11 years; 14% women) who consistently used the monitor for 6 months.
Altogether, they had data on 375 (± 287) app interactions, 3,646 (± 1,417) cuffless readings per user, and 9 (± 7) cuff readings per user.
Traditional cuff SBP averages were calculated monthly and compared with the SBP average of the first month. A t-test analysis was used to detect the difference in SBP between the first and successive months.
On the basis of the mean SBP calculated over 6 months, 136 participants were hypertensive (SBP > 140 mm Hg) and the rest had SBP less than 140 mm Hg.
Hypertensive users saw a statistically significant reduction in SBP of –3.2 mm Hg (95% CI, –0.70 to –5.59; P < .02), beginning at 3 months of continual cuffless BP monitoring, which was sustained through 6 months.
Among users with SBP less than 140 mm Hg, the mean SBP remained unchanged.
“The magnitude of improvement might look modest, but even a 5 mm Hg reduction in systolic BP correlates to a 10% decrease in cardiovascular risk,” Dr. Shah told this news organization.
He noted that “one of the major hurdles is that people may not be aware they have high blood pressure because they don’t feel it. And with a regular cuff, they’ll only see that number when they actually check their blood pressure, which is extremely rare, even for people who have hypertension.”
“Having the ability to show someone their continual blood pressure picture really empowers them to do something to make changes and to be aware, [as well as] to be a more active participant in their health,” Dr. Shah said.
He said that a good analogy is diabetes management, which has transitioned from single finger-stick glucose monitoring to continuous glucose monitoring that provides a complete 24/7 picture of glucose levels.
Transforming technology
Offering perspective on the study, Harlan Krumholz, MD, SM, with Yale New Haven Hospital and Yale School of Medicine, New Haven, Conn., said that having an accurate, affordable, unobtrusive cuffless continuous BP monitor would “transform” BP management.
“This could unlock an era of precision BP management with empowerment of patients to view and act on their numbers,” Dr. Krumholz said in an interview.
“We need data to be confident in the devices – and then research to best leverage the streams of information – and strategies to optimize its use in practice,” Dr. Krumholz added.
“Like any new innovation, we need to mitigate risks and monitor for unintended adverse consequences, but I am bullish on the future of cuffless continuous BP monitors,” Dr. Krumholz said.
Dr. Krumholz said that he “applauds Aktiia for doing studies that assess the effect of the information they are producing on BP over time. We need to know that new approaches not only generate valid information but that they can improve health.”
Ready for prime time?
In June, the European Society of Hypertension issued a statement noting that cuffless BP measurement is a fast-growing and promising field with considerable potential for improving hypertension awareness, management, and control, but because the accuracy of these new devices has not yet been validated, they are not yet suitable for clinical use.
Also providing perspective, Stephen Juraschek, MD, PhD, research director, Hypertension Center of Excellence at Healthcare Associates, Beth Israel Deaconess Medical Center, Boston, said that “there is a lot of interest in cuffless BP monitors due to their ease of measurement, comfort, and ability to obtain BP measurements in multiple settings and environments, and this study showed that the monitoring improved BP over time.”
“It is believed that the increased awareness and feedback may promote healthier behaviors aimed at lowering BP. However, this result should not be conflated with the accuracy of these monitors,” Dr. Juraschek cautioned.
He also noted that there is still no formally approved validation protocol by the Association for the Advancement of Medical Instrumentation.
“While a number of cuffless devices are cleared by the FDA through its 510k mechanism (that is, demonstration of device equivalence), there is no formal stamp of approval or attestation that the measurements are accurate,” Dr. Juraschek said in an interview.
In his view, “more work is needed to understand the validity of these devices. For now, validated, cuff-based home devices are recommended for BP measurement at home, while further work is done to determine the accuracy of these cuffless technologies.”
The study was funded by Aktiia. Dr. Shah is an employee of the company. Dr. Krumholz has no relevant disclosures. Dr. Juraschek is a member of the Validate BP review committee and the AAMI sphygmomanometer committee.
A version of this article first appeared on Medscape.com.
FROM AHA HYPERTENSION 2022
Novel blood test for early-stage liver cancer shows promise
, increasing the likelihood of potentially curative therapy and improved patient prognosis.
HCC accounts for the majority of primary liver cancers and mainly occurs in patients with cirrhosis or chronic hepatitis B virus infection. The prognosis of HCC is poor, largely owing to advanced disease stage at diagnosis.
The current guidelines recommend surveillance with twice-yearly liver ultrasound, with or without serum alpha-fetoprotein, for patients at risk for HCC, although the diagnostic performance is suboptimal.
The new “liquid biopsy” uses HCC-associated extracellular vesicles (EVs) to establish an HCC EV ECG score for distinguishing patients with early-stage HCC from at-risk controls with cirrhosis from a 400-mcL plasma sample.
“We’re the first team looking at extracellular vesicles as a detection biomarker for early-stage liver cancer, and our study showed it had outstanding performance,” study investigator Ju Dong Yang, MD, with Cedars-Sinai Medical Center, Los Angeles, said in a news release.
The study was published online in Hepatology.
In a phase 2 biomarker (case-control) study, the investigators tested their blood test in a training cohort of 106 individuals (45 patients with treatment-naive early-stage HCC and 61 with cirrhosis) and an independent validation cohort with 72 participants (35 patients with treatment-naive early-stage HCC and 37 with cirrhosis).
The HCC EV ECG score had “excellent accuracy” for discriminating between HCC and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.95 and 0.93 in the training and validation cohorts, respectively, they report.
The diagnostic performance “remained excellent” among the subpopulations of HCC etiology and those with tumors within the Milan criteria.
Adding the serum alpha-fetoprotein level to the HCC EV ECG score did not improve its performance.
The researchers say that further validation of the blood test in a larger phase 2 study and a subsequent phase 3 study are needed to confirm its utility in clinical settings.
“We are planning on doing larger-scale studies to further validate this test and bring it into routine clinical practice here – and globally,” Dr. Yang said.
“In addition to its excellent performance, this marker has the advantages of being user friendly, cost efficient, and having a fast turnaround time – within 6 hours from sample collection to result,” Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer, who is not an author on the study, said in the news release.
“Once this marker has been validated in subsequent studies, it can be easily adopted by existing PCR [polymerase chain reaction] facilities,” Dr. Theodorescu added.
The study was supported by an American College of Gastroenterology Junior Faculty Development Award, a Department of Defense Peer Reviewed Cancer Research Program Career Development Award, and the National Institutes of Health. Dr. Yang provides a consulting service for Exact Sciences, Gilead Sciences, and Eisai. Dr. Theodorescu reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, increasing the likelihood of potentially curative therapy and improved patient prognosis.
HCC accounts for the majority of primary liver cancers and mainly occurs in patients with cirrhosis or chronic hepatitis B virus infection. The prognosis of HCC is poor, largely owing to advanced disease stage at diagnosis.
The current guidelines recommend surveillance with twice-yearly liver ultrasound, with or without serum alpha-fetoprotein, for patients at risk for HCC, although the diagnostic performance is suboptimal.
The new “liquid biopsy” uses HCC-associated extracellular vesicles (EVs) to establish an HCC EV ECG score for distinguishing patients with early-stage HCC from at-risk controls with cirrhosis from a 400-mcL plasma sample.
“We’re the first team looking at extracellular vesicles as a detection biomarker for early-stage liver cancer, and our study showed it had outstanding performance,” study investigator Ju Dong Yang, MD, with Cedars-Sinai Medical Center, Los Angeles, said in a news release.
The study was published online in Hepatology.
In a phase 2 biomarker (case-control) study, the investigators tested their blood test in a training cohort of 106 individuals (45 patients with treatment-naive early-stage HCC and 61 with cirrhosis) and an independent validation cohort with 72 participants (35 patients with treatment-naive early-stage HCC and 37 with cirrhosis).
The HCC EV ECG score had “excellent accuracy” for discriminating between HCC and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.95 and 0.93 in the training and validation cohorts, respectively, they report.
The diagnostic performance “remained excellent” among the subpopulations of HCC etiology and those with tumors within the Milan criteria.
Adding the serum alpha-fetoprotein level to the HCC EV ECG score did not improve its performance.
The researchers say that further validation of the blood test in a larger phase 2 study and a subsequent phase 3 study are needed to confirm its utility in clinical settings.
“We are planning on doing larger-scale studies to further validate this test and bring it into routine clinical practice here – and globally,” Dr. Yang said.
“In addition to its excellent performance, this marker has the advantages of being user friendly, cost efficient, and having a fast turnaround time – within 6 hours from sample collection to result,” Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer, who is not an author on the study, said in the news release.
“Once this marker has been validated in subsequent studies, it can be easily adopted by existing PCR [polymerase chain reaction] facilities,” Dr. Theodorescu added.
The study was supported by an American College of Gastroenterology Junior Faculty Development Award, a Department of Defense Peer Reviewed Cancer Research Program Career Development Award, and the National Institutes of Health. Dr. Yang provides a consulting service for Exact Sciences, Gilead Sciences, and Eisai. Dr. Theodorescu reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, increasing the likelihood of potentially curative therapy and improved patient prognosis.
HCC accounts for the majority of primary liver cancers and mainly occurs in patients with cirrhosis or chronic hepatitis B virus infection. The prognosis of HCC is poor, largely owing to advanced disease stage at diagnosis.
The current guidelines recommend surveillance with twice-yearly liver ultrasound, with or without serum alpha-fetoprotein, for patients at risk for HCC, although the diagnostic performance is suboptimal.
The new “liquid biopsy” uses HCC-associated extracellular vesicles (EVs) to establish an HCC EV ECG score for distinguishing patients with early-stage HCC from at-risk controls with cirrhosis from a 400-mcL plasma sample.
“We’re the first team looking at extracellular vesicles as a detection biomarker for early-stage liver cancer, and our study showed it had outstanding performance,” study investigator Ju Dong Yang, MD, with Cedars-Sinai Medical Center, Los Angeles, said in a news release.
The study was published online in Hepatology.
In a phase 2 biomarker (case-control) study, the investigators tested their blood test in a training cohort of 106 individuals (45 patients with treatment-naive early-stage HCC and 61 with cirrhosis) and an independent validation cohort with 72 participants (35 patients with treatment-naive early-stage HCC and 37 with cirrhosis).
The HCC EV ECG score had “excellent accuracy” for discriminating between HCC and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.95 and 0.93 in the training and validation cohorts, respectively, they report.
The diagnostic performance “remained excellent” among the subpopulations of HCC etiology and those with tumors within the Milan criteria.
Adding the serum alpha-fetoprotein level to the HCC EV ECG score did not improve its performance.
The researchers say that further validation of the blood test in a larger phase 2 study and a subsequent phase 3 study are needed to confirm its utility in clinical settings.
“We are planning on doing larger-scale studies to further validate this test and bring it into routine clinical practice here – and globally,” Dr. Yang said.
“In addition to its excellent performance, this marker has the advantages of being user friendly, cost efficient, and having a fast turnaround time – within 6 hours from sample collection to result,” Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer, who is not an author on the study, said in the news release.
“Once this marker has been validated in subsequent studies, it can be easily adopted by existing PCR [polymerase chain reaction] facilities,” Dr. Theodorescu added.
The study was supported by an American College of Gastroenterology Junior Faculty Development Award, a Department of Defense Peer Reviewed Cancer Research Program Career Development Award, and the National Institutes of Health. Dr. Yang provides a consulting service for Exact Sciences, Gilead Sciences, and Eisai. Dr. Theodorescu reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HEPATOLOGY
Game-changing results in fluid resuscitation for acute pancreatitis
Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.
Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.
“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.
The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.
“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.
The WATERFALL trial results were published in the New England Journal of Medicine.
The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
Trial details
The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.
Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.
Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.
A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.
The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).
“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.
This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).
Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.
“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
‘Landmark’ trial
This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.
“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.
Dr. Gardner said the WATERFALL trial results lead to several conclusions.
First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.
Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.
Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.
Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.
“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.
“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.
Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).
A version of this article first appeared on Medscape.com.
Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.
Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.
“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.
The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.
“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.
The WATERFALL trial results were published in the New England Journal of Medicine.
The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
Trial details
The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.
Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.
Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.
A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.
The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).
“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.
This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).
Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.
“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
‘Landmark’ trial
This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.
“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.
Dr. Gardner said the WATERFALL trial results lead to several conclusions.
First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.
Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.
Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.
Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.
“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.
“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.
Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).
A version of this article first appeared on Medscape.com.
Early, aggressive fluid resuscitation in acute pancreatitis led to a higher incidence of fluid overload without improving clinical outcomes in the landmark WATERFALL trial.
Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.
“The WATERFALL trial demonstrates that aggressive fluid resuscitation in acute pancreatitis is not safe, it is not associated with improved outcomes, and it should be abandoned,” Enrique de-Madaria, MD, PhD, with Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization.
The trial settles a “new and clear reference for fluid resuscitation in this frequent disease: lactated Ringer’s solution 1.5 mL/kg per hour (preceded by a 10 mL/kg bolus over 2 hours only in case of hypovolemia),” added Dr. de-Madaria, president of the Spanish Association of Gastroenterology.
“This moderate fluid resuscitation strategy is associated with a much lower frequency of fluid overload and a trend toward improved outcomes. For such reasons, it should be considered as a new standard of care in the early management of acute pancreatitis,” Dr. de-Madaria said.
The WATERFALL trial results were published in the New England Journal of Medicine.
The results are “stunning and, given the carefully crafted trial methods, irrefutable,” Timothy Gardner, MD, with the section of gastroenterology and hepatology, Dartmouth–Hitchcock Medical Center, Lebanon, N.H., wrote in a linked editorial.
Trial details
The trial was conducted at 18 centers across India, Italy, Mexico, and Spain. Patients who presented with acute pancreatitis were randomly allocated to aggressive or moderate resuscitation with lactated Ringer’s solution.
Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg per hour. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg per hour in all patients in this group.
Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to clinical status.
A total of 249 patients were included in the interim analysis – 122 in the aggressive-resuscitation group and 127 in the moderate-resuscitation group.
The data and safety monitoring board terminated the trial at the first interim safety analysis as a result of the development of fluid overload in 20.5% of the patients in the aggressive-resuscitation group versus 6.3% of those in the moderate-resuscitation group (adjusted relative risk, 2.85; 95% confidence interval, 1.36-5.94; P = .004).
“An increased risk of fluid overload was detected in the overall population of patients and also in subgroups of patients without systemic inflammatory response syndrome at baseline, patients with SIRS at baseline (thus, with a higher risk of development of severe pancreatitis), and patients with hypovolemia,” the investigators reported.
This clear signal of harm was coupled with no significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; aRR, 1.30; 95% CI, 0.78-2.18; P = .32).
Patients in the aggressive-resuscitation group spent a median of 6 days in the hospital, compared with 5 days for patients in the moderate-resuscitation group.
“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” the study team wrote.
‘Landmark’ trial
This is a “landmark” trial and “so clinically relevant because of its choice of real world-appropriate aggressive-resuscitation and moderate-resuscitation treatment groups, its use of pancreatitis severity as the main clinical outcome, and its reliance on the carefully defined variable of fluid overload as the main safety outcome,” Dr. Gardner wrote in his editorial.
“Unlike in most other randomized, controlled trials of fluid resuscitation in acute pancreatitis, patients with varying baseline pancreatitis severity were included, and changes in the rate of resuscitation were determined on the basis of a dynamic assessment of hemodynamic testing, imaging, and clinical factors,” he added.
Dr. Gardner said the WATERFALL trial results lead to several conclusions.
First, the need to focus on a steady rate of initial resuscitation – no more than 1.5 mL/kg of body weight per hour. Clinicians should administer a bolus of 10 mL/kg only if there are signs of initial hypovolemia.
Second, that careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload.
Third, that diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes.
Dr. Gardner said the trial also highlights the need to focus research efforts on evaluating other pharmacologic therapies instead of crystalloid fluids.
“Performing randomized controlled trials in acute pancreatitis is notoriously difficult, and the limited human and financial resources that are available for appropriately powered trials in this field post WATERFALL are much better spent on comparative-effectiveness and placebo-controlled trials evaluating new therapeutic agents,” Dr. Gardner said.
“Now that we have gone over the WATERFALL, it is time to look downstream at new targets to treat this challenging disease,” he concluded.
Support for the trial was provided by Instituto de Salud Carlos III, the Spanish Association of Gastroenterology, and ISABIAL (Instituto de Investigación Sanitaria y Biomédica de Alicante).
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Mental health in America: ‘The kids are not alright’
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Should patients stand for office BP readings?
a new study suggests.
Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.
The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Practice changing?
Clinical guidelines recommend office BP be taken in a seated position for most patients.
However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.
At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.
In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.
During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.
Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.
Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.
The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.
“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.
The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.
Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).
The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).
“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization,
Multiple readings most important
Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.
“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.
Dr. Contreras said she takes blood pressure both seated and standing.
“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.
The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests.
Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.
The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Practice changing?
Clinical guidelines recommend office BP be taken in a seated position for most patients.
However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.
At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.
In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.
During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.
Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.
Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.
The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.
“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.
The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.
Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).
The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).
“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization,
Multiple readings most important
Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.
“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.
Dr. Contreras said she takes blood pressure both seated and standing.
“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.
The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new study suggests.
Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.
The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Practice changing?
Clinical guidelines recommend office BP be taken in a seated position for most patients.
However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.
At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.
In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.
During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.
Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.
Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.
The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.
“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.
The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.
Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).
The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).
“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization,
Multiple readings most important
Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.
“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.
Dr. Contreras said she takes blood pressure both seated and standing.
“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.
The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2022
TBI is an unrecognized risk factor for cardiovascular disease
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(CVD). More severe TBI is associated with higher risk of CVD, new research shows.
Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.
The study was published online in JAMA Neurology.
Novel data
Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.
While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.
The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.
In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).
TBIs of all severities were associated with the individual components of the composite outcome, except penetrating TBI and CVD death.
“The association of TBI with subsequent CVD was not attenuated in multivariable models, suggesting that TBI may be accounting for risk that is independent from the other variables,” Dr. Stewart and colleagues wrote.
They noted that the risk was highest shortly after injury, but TBI remained significantly associated with CVD for years after the initial insult.
Why TBI may raise the risk of subsequent CVD remains unclear.
It’s possible that patients with TBI develop more traditional risk factors for CVD through time than do patients without TBI. A study in mice found that TBI led to increased rates of atherosclerosis, the researchers said.
An additional mechanism may be disruption of autonomic regulation, which has been known to occur after TBI.
Another potential pathway is through mental health diagnoses, such as posttraumatic stress disorder; a large body of work has identified associations between PTSD and CVD, including among post-9/11 veterans.
Further work is needed to determine how this risk can be modified to improve outcomes for post-9/11–era veterans, the researchers write.
Unrecognized CVD risk factor?
Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”
“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.
In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”
“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.
The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ketamine promising for rare condition linked to autism
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
Also known as Helsmoortel–Van Der Aa syndrome, ADNP syndrome is caused by mutations in the ADNP gene. Studies in animal models suggest that low-dose ketamine increases expression of ADNP and is neuroprotective.
Intrigued by the preclinical evidence, Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai, New York, and colleagues treated 10 children with ADNP syndrome with a single low dose of ketamine (0.5mg/kg) infused intravenously over 40 minutes. The children ranged in ages 6-12 years.
Using parent-report instruments to assess treatment effects, ketamine was associated with “nominally significant” improvement in a variety of domains, including social behavior, attention-deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parent reports of improvement in these domains aligned with clinician-rated assessments based on the Clinical Global Impressions–Improvement scale.
The results also highlight the potential utility of electrophysiological measurement of auditory steady-state response and eye-tracking to track change with ketamine treatment, the researchers say.
The study was published online in Human Genetics and Genomic (HGG) Advances.
Hypothesis-generating
Ketamine was generally well tolerated. There were no clinically significant abnormalities in laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
Treatment emergent AEs were all mild to moderate and no child required any interventions.
The most common AEs were elation/silliness in five children (50%), all of whom had a history of similar symptoms. Drowsiness and fatigue occurred in four children (40%) and two of them had a history of drowsiness. Aggression was likewise relatively common, reported in four children (40%), all of whom had aggression at baseline.
Decreased appetite emerged as a new AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting, and restlessness each occurred in two children (20%).
The researchers caution that the findings are intended to be “hypothesis generating.”
“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Dr. Kolevzon said in a news release from Mount Sinai.
Ketamine might help ease symptoms of ADNP syndrome “by increasing expression of the ADNP gene or by promoting synaptic plasticity through glutamatergic pathways,” Dr. Kolevzon told this news organization.
The next step, he said, is to get “a larger, placebo-controlled study approved for funding using repeated dosing over a longer duration of time. We are working with the FDA to get the design approved for an investigational new drug application.”
Support for the study was provided by the ADNP Kids Foundation and the Foundation for Mood Disorders. Support for mediKanren was provided by the National Center for Advancing Translational Sciences, and National Institutes of Health through the Biomedical Data Translator Program. Dr. Kolevzon is on the scientific advisory board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics and consults to Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
A version of this article first appeared on Medscape.com.
From Human Genetics and Genomic Advances
Dietary change tops for reducing CVD risk in stage 1 hypertension
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.
Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.
“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.
“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
Be proactive
“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.
“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.
The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.
Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg.
The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.
Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.
The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
Even small changes can help
“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.
“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.
“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.
“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.
Dr. Wallace noted that diet changes don’t have to be drastic.
“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.
“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.
The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.
A version of this article first appeared on Medscape.com.
Clozapine may be best choice for cutting SUD risk in schizophrenia
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
results of a real-world study show.
“Our findings are in line with a recent meta-analysis showing superior efficacy of clozapine in schizophrenia and comorbid SUD and other studies pointing toward clozapine’s superiority over other antipsychotics in the treatment of individuals with schizophrenia and comorbid SUD,” the investigators, led by Jari Tiihonen MD, PhD, department of clinical neuroscience, Karolinska Institutet, Stockholm, write.
“The results on polypharmacy are in line with previous results from nationwide cohorts showing a favorable outcome, compared with oral monotherapies among persons with schizophrenia in general,” they add.
The study was published online Aug. 25 in The British Journal of Psychiatry.
Research gap
Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid SUD is “very sparse, and more importantly, non-existent on the prevention of the development of SUDs in patients with schizophrenia,” the researchers note.
To investigate, they analyzed data on more than 45,000 patients with schizophrenia from Finnish and Swedish national registries, with follow-up lasting 22 years in Finland and 11 years in Sweden.
In patients with schizophrenia without SUD, treatment with clozapine was associated with lowest risk for an initial SUD in both Finland (adjusted hazard ratio, 0.20; 95% confidence interval, 0.16-0.24) and Sweden (aHR, 0.35; 95% CI, 0.24-0.50), compared with no use or use of other antipsychotics.
In Finland, aripiprazole was associated with the second lowest risk for an initial SUD (aHR, 0.36; 95% CI, 0.24-0.55) and antipsychotic polytherapy the third lowest risk (aHR, 0.47; 95% CI, 0.42-0.53).
In Sweden, antipsychotic polytherapy was associated with second lowest risk for an initial SUD (aHR, 0.54; 95% CI, 0.44-0.66) and olanzapine the third lowest risk (aHR, 0.67; 95% CI, 0.53-0.84).
In both countries, the risk for relapse as indicated by psychiatric hospital admission and SUD-related hospital admission were lowest for clozapine, antipsychotic polytherapy and long-acting injectables, the investigators report.
Interpret with caution
Reached for comment, Christoph U. Correll, MD, professor of psychiatry and molecular medicine, the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, urged caution in interpreting the results.
“While the authors are experts in national database analyses and the study was conducted with state-of-the-art methodology, the onset of SUD analyses favoring clozapine are subject to survival bias and order effects,” Dr. Correll said.
“Since clozapine is generally used later in the illness and treatment course, after multiple other antipsychotics have been used, and since SUDs generally occur early in the illness course, most SUDs will already have arisen by the time that clozapine is considered and used,” Dr. Correll said.
“A similar potential bias exists for long-acting injectables (LAIs), as these have generally also been used late in the treatment algorithm,” he noted.
In terms of the significant reduction of SUD-related hospitalizations observed with clozapine, the “order effect” could also be relevant, Dr. Correll said, because over time, patients are less likely to be nonadherent and hospitalized and clozapine is systematically used later in life than other antipsychotics.
“Why antipsychotic polytherapy came out as the second-best treatment is much less clear. Clearly head-to-head randomized trials are needed to follow up on these interesting and intriguing naturalistic database study data,” said Dr. Correll.
This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Dr. Tiihonen and three co-authors have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their institution. Dr. Correll reports having been a consultant and/or advisor to or receiving honoraria from many companies. He has also provided expert testimony for Janssen and Otsuka; served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF PSYCHIATRY