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Novel NSAID–triptan drug effectively relieves migraine pain
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.
In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.
Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.
“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.
The findings were presented at the American Headache Society’s 2021 annual meeting.
Acute treatments needed
For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.
The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.
Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.
In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.
The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.
The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.
Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
Reduced pain progression
Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).
Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).
The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).
In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).
AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).
The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.
“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
Improved adherence?
Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.
AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.
“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.
The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.
Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
Uncertain therapeutic advantage
Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.
“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.
It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.
In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.
For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.
Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.
“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.
“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.
The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.
A version of this article first appeared on Medscape.com.
From AHS 2021
Polypharmacy remains common for autism spectrum patients
Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.
“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.
The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.
In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.
The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.
In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.
The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.
“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.
The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.
“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
Many reasons for multiple medications
“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.
“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.
The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.
The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.
The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.
Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.
“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.
The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.
In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.
The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.
In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.
The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.
“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.
The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.
“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
Many reasons for multiple medications
“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.
“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.
The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.
The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.
The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.
Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.
“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.
The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.
In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.
The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.
In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.
The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.
“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.
The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.
“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
Many reasons for multiple medications
“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.
“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.
The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.
The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.
The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.
FROM JAMA PEDIATRICS
FDA to add myocarditis warning to mRNA COVID-19 vaccines
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
Gray hair goes away and squids go to space
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Scaly beard rash
Waxy loose scale with associated erythema on the face and scalp is a classic sign of seborrheic dermatitis (SD).
SD is caused by inflammation related to the presence of Malassezia, which proliferates on sebum-rich areas of skin. Malassezia is normally present on the skin, but some individuals have a heightened sensitivity to it, leading to erythema and scale. It is prudent to examine the scalp, nasolabial folds, and around the ears where it often occurs concomitantly.
There are multiple topical and systemic options which treat the fungal involvement, the subsequent inflammation, and reduce the scale.1 Topical azole antifungals are effective for reducing the amount of Malassezia present. Topical steroids work well to reduce the erythema. Fortunately, low-potency steroids, including hydrocortisone and desonide, are adequate. This is important since SD frequently involves the face and higher-potency steroids can cause skin atrophy or rebound erythema.
Salicylic acid products exfoliate the scale and topical tar products suppress the scale, both leading to clinical improvement. Sunlight and narrow beam UVB light therapy are also effective treatments. As was true with this patient, SD often improves during the summer months (when there is more sunlight) and when patients shave, as this allows for additional sun exposure to the skin.
The patient in this case was told to use ketoconazole shampoo for his scalp, beard, and mustache. He was instructed to use it at least 3 times per week, applying it to the scalp as the first part of his bathing routine and then waiting until the end to rinse it off. This technique maximizes the antifungal shampoo’s contact time on the skin. He was also given a prescription for ketoconazole cream to apply twice daily to the areas of facial erythema and scale. He was counseled that shaving his beard and mustache might help reduce the SD in those areas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Borda LJ, Perper M, Keri JE. Treatment of seborrheic dermatitis: a comprehensive review. J Dermatolog Treat. 2019;30:158-169. doi: 10.1080/09546634.2018.1473554
Waxy loose scale with associated erythema on the face and scalp is a classic sign of seborrheic dermatitis (SD).
SD is caused by inflammation related to the presence of Malassezia, which proliferates on sebum-rich areas of skin. Malassezia is normally present on the skin, but some individuals have a heightened sensitivity to it, leading to erythema and scale. It is prudent to examine the scalp, nasolabial folds, and around the ears where it often occurs concomitantly.
There are multiple topical and systemic options which treat the fungal involvement, the subsequent inflammation, and reduce the scale.1 Topical azole antifungals are effective for reducing the amount of Malassezia present. Topical steroids work well to reduce the erythema. Fortunately, low-potency steroids, including hydrocortisone and desonide, are adequate. This is important since SD frequently involves the face and higher-potency steroids can cause skin atrophy or rebound erythema.
Salicylic acid products exfoliate the scale and topical tar products suppress the scale, both leading to clinical improvement. Sunlight and narrow beam UVB light therapy are also effective treatments. As was true with this patient, SD often improves during the summer months (when there is more sunlight) and when patients shave, as this allows for additional sun exposure to the skin.
The patient in this case was told to use ketoconazole shampoo for his scalp, beard, and mustache. He was instructed to use it at least 3 times per week, applying it to the scalp as the first part of his bathing routine and then waiting until the end to rinse it off. This technique maximizes the antifungal shampoo’s contact time on the skin. He was also given a prescription for ketoconazole cream to apply twice daily to the areas of facial erythema and scale. He was counseled that shaving his beard and mustache might help reduce the SD in those areas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Waxy loose scale with associated erythema on the face and scalp is a classic sign of seborrheic dermatitis (SD).
SD is caused by inflammation related to the presence of Malassezia, which proliferates on sebum-rich areas of skin. Malassezia is normally present on the skin, but some individuals have a heightened sensitivity to it, leading to erythema and scale. It is prudent to examine the scalp, nasolabial folds, and around the ears where it often occurs concomitantly.
There are multiple topical and systemic options which treat the fungal involvement, the subsequent inflammation, and reduce the scale.1 Topical azole antifungals are effective for reducing the amount of Malassezia present. Topical steroids work well to reduce the erythema. Fortunately, low-potency steroids, including hydrocortisone and desonide, are adequate. This is important since SD frequently involves the face and higher-potency steroids can cause skin atrophy or rebound erythema.
Salicylic acid products exfoliate the scale and topical tar products suppress the scale, both leading to clinical improvement. Sunlight and narrow beam UVB light therapy are also effective treatments. As was true with this patient, SD often improves during the summer months (when there is more sunlight) and when patients shave, as this allows for additional sun exposure to the skin.
The patient in this case was told to use ketoconazole shampoo for his scalp, beard, and mustache. He was instructed to use it at least 3 times per week, applying it to the scalp as the first part of his bathing routine and then waiting until the end to rinse it off. This technique maximizes the antifungal shampoo’s contact time on the skin. He was also given a prescription for ketoconazole cream to apply twice daily to the areas of facial erythema and scale. He was counseled that shaving his beard and mustache might help reduce the SD in those areas.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque
Borda LJ, Perper M, Keri JE. Treatment of seborrheic dermatitis: a comprehensive review. J Dermatolog Treat. 2019;30:158-169. doi: 10.1080/09546634.2018.1473554
Borda LJ, Perper M, Keri JE. Treatment of seborrheic dermatitis: a comprehensive review. J Dermatolog Treat. 2019;30:158-169. doi: 10.1080/09546634.2018.1473554
Performance matters in adenoma detection
Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.
“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.
In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.
Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.
The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.
Endoscopists were classified as having an ADR of less than 25% or 25% and higher.
Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).
By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).
“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”
The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.
“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.
The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
Improve performance, but don’t discount patient factors
The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.
“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.
“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”
The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”
The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.
“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.
In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.
Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.
The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.
Endoscopists were classified as having an ADR of less than 25% or 25% and higher.
Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).
By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).
“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”
The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.
“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.
The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
Improve performance, but don’t discount patient factors
The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.
“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.
“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”
The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”
The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
Low adenoma detection rates (ADRs) were associated with a greater risk of death in colorectal cancer (CRC) patients, especially among those with high-risk adenomas, based on a review of more than 250,000 colonoscopies.
“Both performance quality of the endoscopist as well as specific characteristics of resected adenomas at colonoscopy are associated with colorectal cancer mortality,” but the impact of these combined factors on colorectal cancer mortality has not been examined on a large scale, according to Elisabeth A. Waldmann, MD, of the Medical University of Vienna and colleagues.
In a study published in Clinical Gastroenterology & Hepatology, the researchers reviewed 259,885 colonoscopies performed by 361 endoscopists. Over an average follow-up period of 59 months, 165 CRC-related deaths occurred.
Across all risk groups, CRC mortality was higher among patients whose colonoscopies yielded an ADR of less than 25%, although this was not statistically significant in all groups.
The researchers then stratified patients into those with a negative colonoscopy, those with low-risk adenomas (one to two adenomas less than 10 mm), and those with high-risk adenomas (advanced adenomas or at least three adenomas), with the negative colonoscopy group used as the reference group for comparisons. The average age of the patients was 61 years, and approximately half were women.
Endoscopists were classified as having an ADR of less than 25% or 25% and higher.
Among individuals with low-risk adenomas, CRC mortality was similar whether the ADR on a negative colonoscopy was less than 25% or 25% or higher (adjusted hazard ratios, 1.25 and 1.22, respectively). CRC mortality also remained unaffected by ADR in patients with negatively colonoscopies (aHR, 1.27).
By contrast, individuals with high-risk adenomas had a significantly increased risk of CRC death if their colonoscopy was performed by an endoscopist with an ADR of less than 25%, compared with those whose endoscopists had ADRs of 25% or higher (aHR, 2.25 and 1.35, respectively).
“Our study demonstrated that adding ADR to the risk stratification model improved risk assessment in all risk groups,” the researchers noted. “Importantly, stratification improved most for individuals with high-risk adenomas, the group demanding most resources in health care systems.”
The study findings were limited by several factors including the focus on only screening and surveillance colonoscopies, not including diagnostic colonoscopies, and the inability to adjust for comorbidities and lifestyle factors that might impact CRC mortality, the researchers noted. The 22.4% average ADR in the current study was low, compared with other studies, and could be a limitation as well, although previous guidelines recommend a target ADR of at least 20%.
“Despite the extensive body of literature supporting the importance of ADR in terms of CRC prevention, its implementation into clinical surveillance is challenging,” as physicians under pressure might try to game their ADRs, the researchers wrote.
The findings support the value of mandatory assessment of performance quality, the researchers added. However, “because of the potential possibility of gaming one’s ADR one conclusion drawn by the study results should be that endoscopists’ quality parameters should be monitored and those not meeting the standards trained to improve rather than requiring minimum ADRs as premise for offering screening colonoscopy.”
Improve performance, but don’t discount patient factors
The study is important at this time because colorectal cancer is the third-leading cause of cancer death in the United States, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.
“Screening colonoscopy has been shown to decrease CRC mortality, but factors influencing outcomes after screening colonoscopies remain to be determined,” he said.
“It was expected that high-quality colonoscopy performed by an endoscopist with ADR of 25% or greater was associated with a lower risk for CRC death,” Dr. Sakuraba said. “The strength of the study is that the authors demonstrated that high-quality colonoscopy was more important in individuals with high-risk adenomas, such as advanced adenomas or at least three adenomas.”
The study findings have implications for practice in that they show the importance of monitoring performance quality in screening colonoscopy, Dr. Sakuraba said, “especially when patients have high-risk adenomas.” However, “the authors included only age and sex as variables, but the influence of other factors, such as smoking, [body mass index], and race, need to be studied.”
The researchers had no financial conflicts to disclose. Dr. Sakuraba had no financial conflicts to disclose.
Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
FROM CLINICAL GASTROENTEROLOGY & HEPATOLOGY
HMAs benefit children with relapsed/refractory AML
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
Hypomethylating agents are generally considered to be agents of choice for older adults with acute myeloid leukemia who cannot tolerate the rigors of more intensive therapies, but HMAs also can serve as a bridge to transplant for children and young adults with relapsed or refractory acute myeloid leukemia.
That’s according to Himalee S. Sabnis, MD, MSc and colleagues at Emory University and the Aflac Cancer and Blood Disorders Center at Children’s Healthcare of Atlanta.
In a scientific poster presented during the annual meeting of the American Society of Pediatric Hematology/Oncology, the investigators reported results of a retrospective study of HMA use in patients with relapsed or refractory pediatric AML treated in their center.
Curative intent and palliation
They identified 25 patients (15 boys) with a median age of 8.3 years (range 1.4 to 21 years) with relapsed/refractory AML who received HMAs for curative intent prior to hematopoietic stem cell transplant (HSCT), palliation, or in combination with donor leukocyte infusion (DLI).
Of the 21 patients with relapsed disease, 16 were in first relapse and 5 were in second relapse or greater. Four of the patients had primary refractory disease. The cytogenetic and molecular features were KMT2A rearrangements in six patients, monosomy 7/deletion 7 q in four patients, 8;21 translocation in three patients, and FLT3-ITD mutations in four patients.
The patients received a median of 5.3 HMA cycles each. Of the 133 total HMA cycles, 87 were with azacitidine, and 46 were with decitabine.
HMAs were used as monotherapy in 62% of cycles, and in combination with other therapies in 38%. Of the combinations, 16 were with donor leukocyte infusion, and 9 were gemtuzumab ozogamicin (Mylotarg).
Of the 13 patients for whom HMAs were used as part of treatment plan with curative intent, 5 proceeded to HSCT, and 8 did not. Of the 5 patients, 1 died from transplant-related causes, and 4 were alive post transplant. Of the 8 patients who did not undergo transplant, 1 had chimeric antigen receptor T- cell (CAR T) therapy, and 7 experienced disease progression.
The mean duration of palliative care was 144 days, with patients receiving from one to nine cycles with an HMA, and no treatment interruptions due to toxicity.
Of 5 patients who received donor leukocyte infusions, 3 reached minimal residual disease negativity; all 3 of these patients had late relapses but remained long-term survivors, the investigators reported.
They concluded that “hypomethylating agents can be used effectively as a bridge to transplantation in relapsed and refractory AML with gemtuzumab ozogamicin being the most common agent for combination therapy. Palliation with HMAs is associated with low toxicity and high tolerability in relapsed/refractory AML. Use of HMAs with DLI can induce sustained remissions in some patients.”
The authors propose prospective clinical trials using HMAs in the relapsed/refractory pediatric AML setting in combination with gemtuzumab ozogamicin, alternative targeted agents, and chemotherapy.
HMAs in treatment-related AML
Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, has experience administering HMAs primarily in the adolescent and young adult population with AML.
“Azacitidine and decitabine are good for treatment-related leukemias,” she said in an interview. “They can be used otherwise for people who have relapsed disease and are trying to navigate other options.”
Although they are not standard first-line agents in younger patients, HMAs can play a useful role in therapy for relapsed or refractory disease, she said.
The authors and Dr. Shahani reported having no conflicts of interest to disclose.
FROM THE 2021 ASPHO CONFERENCE
Restricted dietary acid load may reduce odds of migraine
Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.
Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all Ptrend less than .001).
Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).
Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.
Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.
Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.
Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all Ptrend less than .001).
Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).
Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.
Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.
Key clinical point: High dietary acid load was associated with higher odds of migraine. Restricting dietary acid load could therefore reduce the odds of migraine in susceptible patients.
Major finding: The risk for migraine was higher among individuals in highest vs. lowest tertile of dietary acid load measures, including potential renal acid load (odds ratio [OR], 7.208; 95% confidence interval [95% CI], 3.33-15.55), net endogenous acid production (OR, 4.10; 95% CI, 1.92-8.77) scores, and the protein/potassium ratio (OR, 4.12; 95% CI, 1.93-8.81; all Ptrend less than .001).
Study details: Findings are from a case-control study of 1,096 participants including those with migraine (n=514) and healthy volunteers (n=582).
Disclosures: The study was supported by the Iranian Centre of Neurological Research, Neuroscience Institute. All authors declared no conflicts of interest.
Source: Mousavi M et al. Neurol Ther. 2021 Apr 24. doi: 10.1007/s40120-021-00247-2.
Migraine linked to increased hypertension risk in menopausal women
Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.
Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratiomigraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.
Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.
Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.
Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.
Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.
Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratiomigraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.
Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.
Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.
Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.
Key clinical point: Menopausal women with migraine are at a higher risk for incident hypertension.
Major finding: Migraine was associated with an increased risk for incident hypertension (hazard ratiomigraine, 1.29; 95% confidence interval, 1.24-1.35) in menopausal women.
Study details: Findings are from a longitudinal cohort study of 56,202 menopausal women free of hypertension or cardiovascular disease at the age of menopause who participated in the French E3N cohort.
Disclosures: The authors reported no targeted funding. CJ MacDonald and T Kurth received funding and/or honoraria from multiple sources. Other authors had no disclosures relevant to the manuscript.
Source: MacDonald CJ et al. Neurology. 2021 Apr 21. doi: 10.1212/WNL.0000000000011986.
Algorithms for Prediction of Clinical Deterioration on the General Wards: A Scoping Review
The early identification of clinical deterioration among adult hospitalized patients remains a challenge.1 Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.4 In this scoping review, we summarize current algorithms and their evidence.
Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.8 The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.4,10,11
Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.14 The impact of predictive algorithms on the general wards, however, is unclear.
The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.15
MATERIALS AND METHODS
We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).16,17
PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.
All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.
For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.
We defined clinical deterioration as end points, including rapid response team activation, cardiopulmonary resuscitation, transfer to an ICU, or death.
Effects, facilitators, and barriers were identified and categorized using ATLAS.ti 8 software (ATLAS.ti) and evaluated by three researchers (RP, MK, and THvdB). These were categorized using the adapted frameworks of Gagnon et al18 for the barriers and facilitators and of Donabedian19 for the effects (Appendix 3).
The Gagnon et al framework was adapted by changing two of four domains—that is, “Individual” was changed to “Professional” and “Human” to “Physiology.” The domains of “Technology” and “Organization” remained unchanged. The Donabedian domains of “Outcome,” “Process,” and “Structure” also remained unchanged (Table 3).
We divided the studies into two groups: studies on predictive algorithms with and without AI when reporting on characteristics and performance. For the secondary aim of exploring implementation impact, we reported facilitators and barriers in a narrative way, highlighting the most frequent and notable findings.
RESULTS
As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,20,21 Bartkiowak et al,22 Edelson et al,23 Escobar et al,24,25 and Kipnis et al26 reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.20,21,27-29 The resulting 21 papers are included in this review.
Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,30 one study from Portugal,31 and one study from the United Kingdom.32 In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.
Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.
All input variables are presented in Appendix Table 1.
The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).
We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al25 that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.27 A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.35
Effects, Facilitators, and Barriers
As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.
All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.20-23,26-28,34,36-41 Four studies reported real-time detection of deterioration before regular EWS,20,26,42 and three studies reported positive effects on patient-related outcomes.26,35 Four negative effects were noted on the controllability, validity, and potential limitations.27,42
Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.30,32,33,35,39,41 There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.39,42
Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.39 Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.24
The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.24,38
Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.21,23,27,31,33,35,38,41 Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.21,22,24,32,37
DISCUSSION
As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available
There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.44 Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.43 Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores.
Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.25,27,35 Kollef et al27 showed shorter hospitalizations and Evans et al35 found decreased mortality rates in a multimorbid subgroup. Escobar et al25 found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.25 Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al25 should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.
According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1
STRENGTHS AND LIMITATIONS
We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited.
RECOMMENDATIONS FOR FUTURE RESEARCH
Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research.
CONCLUSION
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- Brown H, Terrence J, Vasquez P, Bates DW, Zimlichman E. Continuous monitoring in an inpatient medical-surgical unit: a controlled clinical trial. Am J Med. 2014;127(3):226-232. https://doi.org/10.1016/j.amjmed.2013.12.004
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- Kang MA, Churpek MM, Zadravecz FJ, Adhikari R, Twu NM, Edelson DP: Real-time risk prediction on the wards: a feasibility study. Crit Care Med. 2016;44(8):1468-1473. https://doi.org/10.1097/ccm.0000000000001716
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- Mohamadlou H, Panchavati S, Calvert J, et al. Multicenter validation of a machine-learning algorithm for 48-h all-cause mortality prediction. Health Informatics J. 2020;26(3):1912-1925. https://doi.org/10.1177/1460458219894494
- Alvarez CA, Clark CA, Zhang S, et al. Predicting out of intensive care unit cardiopulmonary arrest or death using electronic medical record data. BMC Med Inform Decis Mak. 2013;13:28. https://doi.org/10.1186/1472-6947-13-28
- Vincent JL, Einav S, Pearse R, et al. Improving detection of patient deterioration in the general hospital ward environment. Eur J Anaesthesiol. 2018;35(5):325-333. https://doi.org/10.1097/eja.0000000000000798
- Romero-Brufau S, Huddleston JM, Escobar GJ, Liebow M. Why the C-statistic is not informative to evaluate early warning scores and what metrics to use. Crit Care. 2015;19(1):285. https://doi.org/10.1186/s13054-015-0999-1
- Weenk M, Bredie SJ, Koeneman M, Hesselink G, van Goor H, van de Belt TH. Continuous monitoring of the vital signs in the general ward using wearable devices: randomized controlled trial. J Med Internet Res. 2020;22(6):e15471. https://doi.org/10.2196/15471
- Wellner B, Grand J, Canzone E, et al. Predicting unplanned transfers to the intensive care unit: a machine learning approach leveraging diverse clinical elements. JMIR Med Inform. 2017;5(4):e45. https://doi.org/10.2196/medinform.8680
- Elliott M, Baird J. Pulse oximetry and the enduring neglect of respiratory rate assessment: a commentary on patient surveillance. Br J Nurs. 2019;28(19):1256-1259. https://doi.org/10.12968/bjon.2019.28.19.1256
- Blackwell JN, Keim-Malpass J, Clark MT, et al. Early detection of in-patient deterioration: one prediction model does not fit all. Crit Care Explor. 2020;2(5):e0116. https://doi.org/10.1097/cce.0000000000000116
- Johnson AEW, Pollard TJ, Shen L, et al. MIMIC-III, a freely accessible critical care database. Sci Data. 2016;3:160035. https://doi.org/10.1038/sdata.2016.35
- Bodenheimer T, Sinsky C. From triple to quadruple aim: care of the patient requires care of the provider. Ann Fam Med. 2014;12(6):573-576. https://doi. org/10.1370/afm.1713
- Kirkland LL, Malinchoc M, O’Byrne M, et al. A clinical deterioration prediction tool for internal medicine patients. Am J Med Qual. 2013;28(2):135-142 https://doi.org/10.1177/1062860612450459
The early identification of clinical deterioration among adult hospitalized patients remains a challenge.1 Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.4 In this scoping review, we summarize current algorithms and their evidence.
Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.8 The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.4,10,11
Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.14 The impact of predictive algorithms on the general wards, however, is unclear.
The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.15
MATERIALS AND METHODS
We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).16,17
PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.
All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.
For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.
We defined clinical deterioration as end points, including rapid response team activation, cardiopulmonary resuscitation, transfer to an ICU, or death.
Effects, facilitators, and barriers were identified and categorized using ATLAS.ti 8 software (ATLAS.ti) and evaluated by three researchers (RP, MK, and THvdB). These were categorized using the adapted frameworks of Gagnon et al18 for the barriers and facilitators and of Donabedian19 for the effects (Appendix 3).
The Gagnon et al framework was adapted by changing two of four domains—that is, “Individual” was changed to “Professional” and “Human” to “Physiology.” The domains of “Technology” and “Organization” remained unchanged. The Donabedian domains of “Outcome,” “Process,” and “Structure” also remained unchanged (Table 3).
We divided the studies into two groups: studies on predictive algorithms with and without AI when reporting on characteristics and performance. For the secondary aim of exploring implementation impact, we reported facilitators and barriers in a narrative way, highlighting the most frequent and notable findings.
RESULTS
As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,20,21 Bartkiowak et al,22 Edelson et al,23 Escobar et al,24,25 and Kipnis et al26 reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.20,21,27-29 The resulting 21 papers are included in this review.
Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,30 one study from Portugal,31 and one study from the United Kingdom.32 In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.
Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.
All input variables are presented in Appendix Table 1.
The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).
We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al25 that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.27 A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.35
Effects, Facilitators, and Barriers
As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.
All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.20-23,26-28,34,36-41 Four studies reported real-time detection of deterioration before regular EWS,20,26,42 and three studies reported positive effects on patient-related outcomes.26,35 Four negative effects were noted on the controllability, validity, and potential limitations.27,42
Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.30,32,33,35,39,41 There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.39,42
Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.39 Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.24
The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.24,38
Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.21,23,27,31,33,35,38,41 Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.21,22,24,32,37
DISCUSSION
As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available
There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.44 Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.43 Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores.
Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.25,27,35 Kollef et al27 showed shorter hospitalizations and Evans et al35 found decreased mortality rates in a multimorbid subgroup. Escobar et al25 found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.25 Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al25 should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.
According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1
STRENGTHS AND LIMITATIONS
We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited.
RECOMMENDATIONS FOR FUTURE RESEARCH
Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research.
CONCLUSION
The early identification of clinical deterioration among adult hospitalized patients remains a challenge.1 Delayed identification is associated with increased morbidity and mortality, unplanned intensive care unit (ICU) admissions, prolonged hospitalization, and higher costs.2,3 Earlier detection of deterioration using predictive algorithms of vital sign monitoring might avoid these negative outcomes.4 In this scoping review, we summarize current algorithms and their evidence.
Vital signs provide the backbone for detecting clinical deterioration. Early warning scores (EWS) and outreach protocols were developed to bring structure to the assessment of vital signs. Most EWS claim to predict clinical end points such as unplanned ICU admission up to 24 hours in advance.5,6 Reviews of EWS showed a positive trend toward reduced length of stay and mortality. However, conclusions about general efficacy could not be generated because of case heterogeneity and methodologic shortcomings.4,7 Continuous automated vital sign monitoring of patients on the general ward can now be accomplished with wearable devices.8 The first reports on continuous monitoring showed earlier detection of deterioration but not improved clinical end points.4,9 Since then, different reports on continuous monitoring have shown positive effects but concluded that unprocessed monitoring data per se falls short of generating actionable alarms.4,10,11
Predictive algorithms, which often use artificial intelligence (AI), are increasingly employed to recognize complex patterns or abnormalities and support predictions of events in big data sets.12,13 Especially when combined with continuous vital sign monitoring, predictive algorithms have the potential to expedite detection of clinical deterioration and improve patient outcomes. Predictive algorithms using vital signs in the ICU have shown promising results.14 The impact of predictive algorithms on the general wards, however, is unclear.
The aims of our scoping review were to explore the extent and range of and evidence for predictive vital signs–based algorithms on the adult general ward; to describe the variety of these algorithms; and to categorize effects, facilitators, and barriers of their implementation.15
MATERIALS AND METHODS
We performed a scoping review to create a summary of the current state of research. We used the five-step method of Levac and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews guidelines (Appendix 1).16,17
PubMed, Embase, and CINAHL databases were searched for English-language articles written between January 1, 2010, and November 20, 2020. We developed the search queries with an experienced information scientist, and we used database-specific terms and strategies for input, clinical outcome, method, predictive capability, and population (Appendix 2). Additionally, we searched the references of the selected articles, as well as publications citing these articles.
All studies identified were screened by title and abstract by two researchers (RP and YE). The selected studies were read in their entirety and checked for eligibility using the following inclusion criteria: automated algorithm; vital signs-based; real-time prediction; of clinical deterioration; in an adult, general ward population. In cases where there were successive publications with the same algorithm and population, we selected the most recent study.
For screening and selection, we used the Rayyan QCRI online tool (Qatar Computing Research Institute) and Endnote X9 (Clarivate Analytics). We extracted information using a data extraction form and organized it into descriptive characteristics of the selected studies (Table 1): an input data table showing number of admissions, intermittent or continuous measurements, vital signs measured, laboratory results (Appendix Table 1), a table summarizing study designs and settings (Appendix Table 2), and a prediction performance table (Table 2). We report characteristics of the populations and algorithms, prediction specifications such as area under the receiver operating curve (AUROC), and predictive values. Predictive values are affected by prevalence, which may differ among populations. To compare the algorithms, we calculated an indexed positive predictive value (PPV) and a number needed to evaluate (NNE) using a weighted average prevalence of clinical deterioration of 3.0%.
We defined clinical deterioration as end points, including rapid response team activation, cardiopulmonary resuscitation, transfer to an ICU, or death.
Effects, facilitators, and barriers were identified and categorized using ATLAS.ti 8 software (ATLAS.ti) and evaluated by three researchers (RP, MK, and THvdB). These were categorized using the adapted frameworks of Gagnon et al18 for the barriers and facilitators and of Donabedian19 for the effects (Appendix 3).
The Gagnon et al framework was adapted by changing two of four domains—that is, “Individual” was changed to “Professional” and “Human” to “Physiology.” The domains of “Technology” and “Organization” remained unchanged. The Donabedian domains of “Outcome,” “Process,” and “Structure” also remained unchanged (Table 3).
We divided the studies into two groups: studies on predictive algorithms with and without AI when reporting on characteristics and performance. For the secondary aim of exploring implementation impact, we reported facilitators and barriers in a narrative way, highlighting the most frequent and notable findings.
RESULTS
As shown in the Figure, we found 1741 publications, of which we read the full-text of 109. There were 1632 publications that did not meet the inclusion criteria. The publications by Churpek et al,20,21 Bartkiowak et al,22 Edelson et al,23 Escobar et al,24,25 and Kipnis et al26 reported on the same algorithms or databases but had significantly different approaches. For multiple publications using the same algorithm and population, the most recent was named with inclusion of the earlier findings.20,21,27-29 The resulting 21 papers are included in this review.
Descriptive characteristics of the studies are summarized in Table 1. Nineteen of the publications were full papers and two were conference abstracts. Most of the studies (n = 18) were from the United States; there was one study from South Korea,30 one study from Portugal,31 and one study from the United Kingdom.32 In 15 of the studies, there was a strict focus on general or specific wards; 6 studies also included the ICU and/or emergency departments.
Two of the studies were clinical trials, 2 were prospective observational studies, and 17 were retrospective studies. Five studies reported on an active predictive model during admission. Of these, 3 reported that the model was clinically implemented, using the predictions in their clinical workflow. None of the implemented studies used AI.
All input variables are presented in Appendix Table 1.
The non-AI algorithm prediction horizons ranged from 4 to 24 hours, with a median of 24 hours (interquartile range [IQR], 12-24 hours). The AI algorithms ranged from 2 to 48 hours and had a median horizon of 14 hours (IQR, 12-24 hours).
We found three studies reporting patient outcomes. The most recent of these was a large multicenter implementation study by Escobar et al25 that included an extensive follow-up response. This study reported a significantly decreased 30-day mortality in the intervention cohort. A smaller randomized controlled trial reported no significant differences in patient outcomes with earlier warning alarms.27 A third study reported more appropriate rapid response team deployment and decreased mortality in a subgroup analysis.35
Effects, Facilitators, and Barriers
As shown in the Appendix Figure and further detailed in Table 3, the described effects were predominantly positive—57 positive effects vs 11 negative effects. These positive effects sorted primarily into the outcome and process domains.
All of the studies that compared their proposed model with one of various warning systems (eg, EWS, National Early Warning Score [NEWS], Modified Early Warning Score [MEWS]) showed superior performance (based on AUROC and reported predictive values). In 17 studies, the authors reported their model as more useful or superior to the EWS.20-23,26-28,34,36-41 Four studies reported real-time detection of deterioration before regular EWS,20,26,42 and three studies reported positive effects on patient-related outcomes.26,35 Four negative effects were noted on the controllability, validity, and potential limitations.27,42
Of the 38 remarks in the Technology domain, difficulty with implementation in daily practice was a commonly cited barrier.22,24,40,42 Difficulties included creating real-time data feeds out of the EMR, though there were mentions of some successful examples.25,27,36 Difficulty in the interpretability of AI was also considered a potential barrier.30,32,33,35,39,41 There were remarks as to the applicability of the prolonged prediction horizon because of the associated decoupling from the clinical view.39,42
Conservative attitudes toward new technologies and inadequate knowledge were mentioned as barriers.39 Repeated remarks were made on the difficulty of interpreting and responding to a predicted escalation, as the clinical pattern might not be recognizable at such an early stage. On the other hand, it is expected that less invasive countermeasures would be adequate to avert further escalation. Earlier recognition of possible escalations also raised potential ethical questions, such as when to discuss palliative care.24
The heterogeneity of the general ward population and the relatively low prevalence of deterioration were mentioned as barriers.24,30,38,41 There were also concerns that not all escalations are preventable and that some patient outcomes may not be modifiable.24,38
Many investigators expected reductions in false alarms and associated alarm fatigue (reflected as higher PPVs). Furthermore, they expected workflow to improve and workload to decrease.21,23,27,31,33,35,38,41 Despite the capacity of modern EMRs to store large amounts of patient data, some investigators felt improvements to real-time access, data quality and validity, and data density are needed to ensure valid associated predictions.21,22,24,32,37
DISCUSSION
As the complexity and comorbidity of hospitalized adults grow, predicting clinical deterioration is becoming more important. With an ever-increasing amount of available
There are several important limitations across these studies. In a clinical setting, these models would function as a screening test. Almost all studies report an AUROC; however, sensitivity and PPV or NNE (defined as 1/PPV) may be more useful than AUROC when predicting low-frequency events with high-potential clinical impact.44 Assessing the NNE is especially relevant because of its relation to alarm fatigue and responsiveness of clinicians.43 Alarm fatigue and lack of adequate response to alarms were repeatedly cited as potential barriers for application of automated scores.
Although the results of our scoping review are promising, there are limited data on clinical outcomes using these algorithms. Only three of five algorithms were used to guide clinical decision-making.25,27,35 Kollef et al27 showed shorter hospitalizations and Evans et al35 found decreased mortality rates in a multimorbid subgroup. Escobar et al25 found an overall and consistent decrease in mortality in a large, heterogenic population of inpatients across 21 hospitals. While Escobar et al’s findings provide strong evidence that predictive algorithms and structured follow-up on alarms can improve patient outcomes, it recognizes that not all facilities will have the resources to implement them.25 Dedicated round-the-clock follow-up of alarms has yet to be proven feasible for smaller institutions, and leaner solutions must be explored. The example set by Escobar et al25 should be translated into various settings to prove its reproducibility and to substantiate the clinical impact of predictive models and structured follow-up.
According to expert opinion, the use of high-frequency or continuous monitoring at low-acuity wards and AI algorithms to detect trends and patterns will reduce failure-to-rescue rates.4,9,43 However, most studies in our review focused on periodic spot-checked vital signs, and none of the AI algorithms were implemented in clinical care (Appendix Table 1
STRENGTHS AND LIMITATIONS
We performed a comprehensive review of the current literature using a clear and reproducible methodology to minimize the risk of missing relevant publications. The identified research is mainly limited to large US centers and consists of mostly retrospective studies. Heterogeneity among inputs, endpoints, time horizons, and evaluation metrics make comparisons challenging. Comments on facilitators, barriers, and effects were limited.
RECOMMENDATIONS FOR FUTURE RESEARCH
Artificial intelligence and the use of continuous monitoring hold great promise in creating optimal predictive algorithms. Future studies should directly compare AI- and non-AI-based algorithms using continuous monitoring to determine predictive accuracy, feasibility, costs, and outcomes. A consensus on endpoint definitions, input variables, methodology, and reporting is needed to enhance reproducibility, comparability, and generalizability of future research.
CONCLUSION
- van Galen LS, Struik PW, Driesen BEJM, et al. Delayed recognition of deterioration of patients in general wards is mostly caused by human related monitoring failures: a root cause analysis of unplanned ICU admissions. PLoS One. 2016;11(8):e0161393. https://doi.org/10.1371/journal. pone.0161393
- Mardini L, Lipes J, Jayaraman D. Adverse outcomes associated with delayed intensive care consultation in medical and surgical inpatients. J Crit Care. 2012;27(6):688-693. https://doi.org/10.1016/j.jcrc.2012.04.011
- Young MP, Gooder VJ, McBride K, James B, Fisher ES. Inpatient transfers to the intensive care unit: delays are associated with increased mortality and morbidity. J Gen Intern Med. 2003;18(2):77-83. https://doi.org/10.1046/ j.1525-1497.2003.20441.x
- Khanna AK, Hoppe P, Saugel B. Automated continuous noninvasive ward monitoring: future directions and challenges. Crit Care. 2019;23(1):194. https://doi.org/10.1186/s13054-019-2485-7
- Ludikhuize J, Hamming A, de Jonge E, Fikkers BG. Rapid response systems in The Netherlands. Jt Comm J Qual Patient Saf. 2011;37(3):138-197. https:// doi.org/10.1016/s1553-7250(11)37017-1
- Cuthbertson BH, Boroujerdi M, McKie L, Aucott L, Prescott G. Can physiological variables and early warning scoring systems allow early recognition of the deteriorating surgical patient? Crit Care Med. 2007;35(2):402-409. https://doi.org/10.1097/01.ccm.0000254826.10520.87
- Alam N, Hobbelink EL, van Tienhoven AJ, van de Ven PM, Jansma EP, Nanayakkara PWB. The impact of the use of the Early Warning Score (EWS) on patient outcomes: a systematic review. Resuscitation. 2014;85(5):587-594. https://doi.org/10.1016/j.resuscitation.2014.01.013
- Weenk M, Koeneman M, van de Belt TH, Engelen LJLPG, van Goor H, Bredie SJH. Wireless and continuous monitoring of vital signs in patients at the general ward. Resuscitation. 2019;136:47-53. https://doi.org/10.1016/j.resuscitation.2019.01.017
- Cardona-Morrell M, Prgomet M, Turner RM, Nicholson M, Hillman K. Effectiveness of continuous or intermittent vital signs monitoring in preventing adverse events on general wards: a systematic review and meta-analysis. Int J Clin Pract. 2016;70(10):806-824. https://doi.org/10.1111/ijcp.12846
- Brown H, Terrence J, Vasquez P, Bates DW, Zimlichman E. Continuous monitoring in an inpatient medical-surgical unit: a controlled clinical trial. Am J Med. 2014;127(3):226-232. https://doi.org/10.1016/j.amjmed.2013.12.004
- Mestrom E, De Bie A, van de Steeg M, Driessen M, Atallah L, Bezemer R. Implementation of an automated early warning scoring system in a E8 Journal of Hospital Medicine® Published Online June 2021 An Official Publication of the Society of Hospital Medicine Peelen et al | Predicting Deterioration: A Scoping Review surgical ward: practical use and effects on patient outcomes. PLoS One. 2019;14(5):e0213402. https://doi.org/10.1371/journal.pone.0213402
- Jiang F, Jiang Y, Zhi H, et al. Artificial intelligence in healthcare: past, present and future. Stroke Vasc Neurol. 2017;2(4):230-243. https://doi.org/10.1136/ svn-2017-000101
- Iwashyna TJ, Liu V. What’s so different about big data? A primer for clinicians trained to think epidemiologically. Ann Am Thorac Soc. 2014;11(7):1130- 1135. https://doi.org/10.1513/annalsats.201405-185as
- Jalali A, Bender D, Rehman M, Nadkanri V, Nataraj C. Advanced analytics for outcome prediction in intensive care units. Conf Proc IEEE Eng Med Biol Soc. 2016;2016:2520-2524. https://doi.org/10.1109/embc.2016.7591243
- Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol. 2018;18(1):143. https://doi.org/10.1186/s12874-018-0611-x
- Arksey H, O’Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol. 2005;8(1):19-32. https://doi.org/10.1080/13645 57032000119616
- Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMAScR): checklist and explanation. Ann Intern Med. 2018;169(7):467- 473. https://doi.org/10.7326/m18-0850
- Gagnon MP, Desmartis M, Gagnon J, et al. Framework for user involvement in health technology assessment at the local level: views of health managers, user representatives, and clinicians. Int J Technol Assess Health Care. 2015;31(1-2):68-77. https://doi.org/10.1017/s0266462315000070
- Donabedian A. The quality of care. How can it be assessed? JAMA. 1988;260(12):1743-1748. https://doi.org/10.1001/jama.260.12.1743
- Churpek MM, Yuen TC, Winslow C, et al. Multicenter development and validation of a risk stratification tool for ward patients. Am J Respir Crit Care Med. 2014;190(6):649-655. https://doi.org/10.1164/rccm.201406-1022oc
- Churpek MM, Yuen TC, Winslow C, Meltzer DO, Kattan MW, Edelson DP. Multicenter comparison of machine learning methods and conventional regression for predicting clinical deterioration on the wards. Crit Care Med. 2016;44(2):368-374. https://doi.org/10.1097/ccm.0000000000001571
- Bartkowiak B, Snyder AM, Benjamin A, et al. Validating the electronic cardiac arrest risk triage (eCART) score for risk stratification of surgical inpatients in the postoperative setting: retrospective cohort study. Ann Surg. 2019;269(6):1059-1063. https://doi.org/10.1097/sla.0000000000002665
- Edelson DP, Carey K, Winslow CJ, Churpek MM. Less is more: detecting clinical deterioration in the hospital with machine learning using only age, heart rate and respiratory rate. Abstract presented at: American Thoracic Society International Conference; May 22, 2018; San Diego, California. Am J Resp Crit Care Med. 2018;197:A4444.
- Escobar GJ, LaGuardia JC, Turk BJ, Ragins A, Kipnis P, Draper D. Early detection of impending physiologic deterioration among patients who are not in intensive care: development of predictive models using data from an automated electronic medical record. J Hosp Med. 2012;7(5):388-395. https:// doi.org/10.1002/jhm.1929
- Escobar GJ, Liu VX, Schuler A, Lawson B, Greene JD, Kipnis P. Automated identification of adults at risk for in-hospital clinical deterioration. N Engl J Med. 2020;383(20):1951-1960. https://doi.org/10.1056/nejmsa2001090
- Kipnis P, Turk BJ, Wulf DA, et al. Development and validation of an electronic medical record-based alert score for detection of inpatient deterioration outside the ICU. J Biomed Inform. 2016;64:10-19. https://doi.org/10.1016/j. jbi.2016.09.013
- Kollef MH, Chen Y, Heard K, et al. A randomized trial of real-time automated clinical deterioration alerts sent to a rapid response team. J Hosp Med. 2014;9(7):424-429. https://doi.org/10.1002/jhm.2193
- Hackmann G, Chen M, Chipara O, et al. Toward a two-tier clinical warning system for hospitalized patients. AMIA Annu Symp Proc. 2011;2011:511-519.
- Bailey TC, Chen Y, Mao Y, Lu, C, Hackmann G, Micek ST. A trial of a real-time alert for clinical deterioration in patients hospitalized on general medical wards. J Hosp Med. 2013;8(5):236-242. https://doi.org/10.1002/jhm.2009
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