Continuous intracranial electroencephalography (cEEG) may help pinpoint optimal timing of diagnostic studies and treatment for patients with focal epilepsy, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.

“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.

The study was published online Feb. 8 in JAMA Neurology.
 

Distinct chronotypes

Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.

Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.

To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.

After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.

Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.

To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.

To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.

Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.

The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.

The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).

Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.

Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.

Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.

“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”

The results support patients’ impressions that their seizures occur in a cyclical pattern.

“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.

“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
 

Need for more research

Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”

The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.

The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.

However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.

“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.

“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”

The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Continuous intracranial electroencephalography (cEEG) may help pinpoint optimal timing of diagnostic studies and treatment for patients with focal epilepsy, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.

“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.

The study was published online Feb. 8 in JAMA Neurology.
 

Distinct chronotypes

Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.

Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.

To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.

After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.

Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.

To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.

To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.

Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.

The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.

The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).

Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.

Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.

Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.

“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”

The results support patients’ impressions that their seizures occur in a cyclical pattern.

“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.

“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
 

Need for more research

Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”

The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.

The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.

However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.

“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.

“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”

The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Continuous intracranial electroencephalography (cEEG) may help pinpoint optimal timing of diagnostic studies and treatment for patients with focal epilepsy, new research suggests. Findings from a large longitudinal study show that seizure onset in patients with focal epilepsy follows circadian, multiday, and annual cycles.

“Although daily and multiday rhythms have previously been identified, the extent to which these nonrandom rhythms exist in a larger cohort has been unclear,” said study investigator Joline Marie Fan, MD, a clinical fellow at the University of California, San Francisco. “This means that a patient with epilepsy may have a unique combination of seizure rhythms that can inform the days and timing of his or her highest seizure risk,” she added.

The study was published online Feb. 8 in JAMA Neurology.
 

Distinct chronotypes

Clinicians and patients alike have long observed cyclical patterns in the onset of epileptic seizures. However, such patterns have rarely been measured in a quantitative way.

Previous studies have examined seizure cycles using inpatient seizure monitoring and patients’ seizure diaries, but the duration of these recordings and their accuracy have been limited. Within the past decade, the advent of cEEG has allowed researchers to observe the cyclical pattern of interictal epileptiform activity, but the numbers of patients involved in such studies have been limited.

To investigate seizure chronotypes in greater detail, the researchers examined retrospective data for 222 adults with medically refractory focal epilepsy who took part in clinical trials of the NeuroPace responsive neurostimulation (RNS) system.

After implantation in the brain, this system monitors the seizure focus or foci continuously and delivers stimulation to stop seizures. Participants also kept seizure diaries and classified their seizures as simple motor, simple other, complex partial, and generalized tonic-clonic.

Dr. Fan’s group examined three subpopulations of patients to investigate three durations of seizure cycles. They examined self-reported disabling seizures, electrographic seizures, and interictal epileptiform activity. Because patients did not record the time of their disabling seizures, the investigators examined them only in multidien and circannual cycles.

To examine circannual seizure cycles, the investigators included 194 patients who kept continuous seizure diaries for 2 or more years and who reported 24 or more days in which disabling seizures occurred.

To examine multidien seizure cycles, they included 186 participants who reported 24 or more days with disabling seizures over a period of 6 or more months during which the RNS system collected cEEG data. They included 85 patients who had 48 hours or more in which electrographic seizure counts were above zero during 6 or more months of cEEG data collection to examine circadian seizure cycles.

Phase-locking value (PLV) was used to determine the strength of a cycle (i.e., the degree of consistency with which seizures occur during certain phases of a cycle). A PLV of 0 represents a uniform distribution of events during various phases of a cycle; a PLV of 1 indicates that all events occur exactly at the same phase of a cycle.

The population’s median age was 35 years, and the sample included approximately equal numbers of men and women. Patients’ focal epilepsies included mesiotemporal (57.2%), frontal (14.0%), neocortical-temporal (9.9%), parietal (4.1%), occipital (1.4%), and multifocal (13.5%). The data included 1,118 patient-years of cEEG, 754,108 electrographic seizures, and 313,995 self-reported seizures.

The prevalence of statistically significant circannual seizure cycles in this population was 12%. The prevalence of multidien seizure cycles was 60%, and the prevalence of circadian seizure cycles was 89%. Multidien cycles (mean PLV, 0.34) and circadian cycles (mean PLV, 0.34) were stronger than were circannual cycles (mean PLV, 0.17).

Among patients with circannual seizure cycles, there was a weak to moderate tendency for seizures to occur during one of the four seasons. There was no overall trend toward seizure onset in one season among this group.

Among patients with multidien seizure cycles, investigators identified five patterns of interictal epileptiform activity fluctuations. One pattern had irregular periodicity, and the others reached peak periodicity at 7, 15, 20, and 30 days. For some patients, one or more periodicities occurred. For most patients, electrographic or self-reported seizures tended to occur on the rising phase of the interictal epileptiform activity cycle. Interictal epileptiform activity increased on days around seizures.

Results showed there were five main seizure peak times among patients with circadian seizure cycles: midnight, 3:00 a.m., 9:00 a.m., 2:00 p.m., and 6:00 p.m. These findings corroborate the observations of previous investigations, the researchers noted. Hourly interictal epileptiform activity peaked during the night, regardless of peak seizure time.

“Although the neurostimulation device offers us a unique opportunity to investigate electrographic seizure activity quantitatively, the generalizability of our study is limited to the patient cohort that we studied,” said Dr. Fan. “The study findings are limited to patients with neurostimulation devices used for intractable focal epilepsies.”

The results support patients’ impressions that their seizures occur in a cyclical pattern.

“Ultimately, these findings will be helpful for developing models to aid with seizure forecasting and prediction in order to help reduce the uncertainty of seizure timing for patients with epilepsy,” said Dr. Fan.

“Other implications include optimizing the timing for patients to be admitted into the hospital for seizure characterization based on their seizure chronotype, or possibly tailoring a medication regimen in accordance with a patient’s seizure cycles,” she added.
 

Need for more research

Commenting on the findings, Tobias Loddenkemper, MD, professor of neurology at Harvard Medical School, Boston, noted that the study is “one of the largest longitudinal seizure pattern analyses, based on the gold standard of intracranially recorded epileptic seizures.”

The research, he added, extends neurologists’ understanding of seizure patterns over time, expands knowledge about seizure chronotypes, and emphasizes a relationship between interictal epileptiform activity and seizures.

The strengths of the study include the recording of seizures with intracranial EEG, its large number of participants, and the long duration of recordings, Dr. Loddenkemper said.

However, he said, it is important to note that self-reports are not always reliable. The results may also reflect the influence of potential confounders of seizure patterns, such as seizure triggers, treatment, stimulation, or sleep-wake, circadian, or hormonal cycles, he added.

“In the short term, validation studies, as well as confirmatory studies with less invasive sensors, may be needed,” said Dr. Loddenkemper.

“This could potentially include a trial that confirms findings prospectively, utilizing results from video EEG monitoring admissions. In the long term, seizure detection and prediction, as well as interventional chronotherapeutic trials, may be enabled, predicting seizures in individual patients and treating at times of greatest seizure susceptibility.”

The study was supported by grants to some of the authors from the Wyss Center for Bio and Neuroengineering, the Ernest Gallo Foundation, the Swiss National Science Foundation, and the Velux Stiftung. Dr. Fan has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Successful innovation requires experimentation, according to a recent editorial in BMJ Quality & Safety – that’s why health systems should engage in more experimenting, more systematically, to improve health care.

“Most health systems implement interventions without testing them against other designs,” said co-author Mitesh S. Patel, MD, MBA, MS, of the University of Pennsylvania, Philadelphia. “This means that good ideas are often not spread (because we don’t know how impactful they are) and bad ones persist (because we don’t realize they don’t work).”

Dr. Patel, who is director of the Penn Medicine Nudge Unit at the Perelman Center for Advanced Medicine, encourages health systems and clinicians to implement new interventions in testable ways such as through a randomized trial, so that we can learn what works and why. A more systematic approach could help to expand programs that work and improve workflow and patient care.

“First, we must embed research teams within health systems in order to create the capacity for this kind of work. Expertise is required to identify a promising intervention, design the conceptual approach, conduct the technical implementation and rigorously evaluate the trial. These teams are also able to design interventions within the context of existing workflows in order to ensure that successful projects can be quickly scaled and that ineffective initiatives can be seamlessly terminated.” the authors wrote.

“Second, we must take advantage of existing data systems. The field of health care is ripe with detailed and reliable administrative data and electronic medical record data. These data offer the potential to do high-quality, low-cost, rapid trials. Third, we must measure a wide range of meaningful outcomes. We should examine the effect of interventions on health care costs, health care utilization and health outcomes.”

Next steps could be focused on thinking about the key priority areas and how can experiments be used to generate new knowledge on what works and what does not. “Luckily, the complex world of health care provides endless opportunities for rapid-cycle, randomized trials that target health care costs and outcomes,” Dr. Patel said.
 

Reference

1. Oakes AH, Patel MS. A nudge towards increased experimentation to more rapidly improve healthcare. BMJ Qual Saf. 2020;29:179-181. doi: 10.1136/bmjqs-2019-009948. Accessed Dec 3, 2019.

Successful innovation requires experimentation, according to a recent editorial in BMJ Quality & Safety – that’s why health systems should engage in more experimenting, more systematically, to improve health care.

“Most health systems implement interventions without testing them against other designs,” said co-author Mitesh S. Patel, MD, MBA, MS, of the University of Pennsylvania, Philadelphia. “This means that good ideas are often not spread (because we don’t know how impactful they are) and bad ones persist (because we don’t realize they don’t work).”

Dr. Patel, who is director of the Penn Medicine Nudge Unit at the Perelman Center for Advanced Medicine, encourages health systems and clinicians to implement new interventions in testable ways such as through a randomized trial, so that we can learn what works and why. A more systematic approach could help to expand programs that work and improve workflow and patient care.

“First, we must embed research teams within health systems in order to create the capacity for this kind of work. Expertise is required to identify a promising intervention, design the conceptual approach, conduct the technical implementation and rigorously evaluate the trial. These teams are also able to design interventions within the context of existing workflows in order to ensure that successful projects can be quickly scaled and that ineffective initiatives can be seamlessly terminated.” the authors wrote.

“Second, we must take advantage of existing data systems. The field of health care is ripe with detailed and reliable administrative data and electronic medical record data. These data offer the potential to do high-quality, low-cost, rapid trials. Third, we must measure a wide range of meaningful outcomes. We should examine the effect of interventions on health care costs, health care utilization and health outcomes.”

Next steps could be focused on thinking about the key priority areas and how can experiments be used to generate new knowledge on what works and what does not. “Luckily, the complex world of health care provides endless opportunities for rapid-cycle, randomized trials that target health care costs and outcomes,” Dr. Patel said.
 

Reference

1. Oakes AH, Patel MS. A nudge towards increased experimentation to more rapidly improve healthcare. BMJ Qual Saf. 2020;29:179-181. doi: 10.1136/bmjqs-2019-009948. Accessed Dec 3, 2019.

Successful innovation requires experimentation, according to a recent editorial in BMJ Quality & Safety – that’s why health systems should engage in more experimenting, more systematically, to improve health care.

“Most health systems implement interventions without testing them against other designs,” said co-author Mitesh S. Patel, MD, MBA, MS, of the University of Pennsylvania, Philadelphia. “This means that good ideas are often not spread (because we don’t know how impactful they are) and bad ones persist (because we don’t realize they don’t work).”

Dr. Patel, who is director of the Penn Medicine Nudge Unit at the Perelman Center for Advanced Medicine, encourages health systems and clinicians to implement new interventions in testable ways such as through a randomized trial, so that we can learn what works and why. A more systematic approach could help to expand programs that work and improve workflow and patient care.

“First, we must embed research teams within health systems in order to create the capacity for this kind of work. Expertise is required to identify a promising intervention, design the conceptual approach, conduct the technical implementation and rigorously evaluate the trial. These teams are also able to design interventions within the context of existing workflows in order to ensure that successful projects can be quickly scaled and that ineffective initiatives can be seamlessly terminated.” the authors wrote.

“Second, we must take advantage of existing data systems. The field of health care is ripe with detailed and reliable administrative data and electronic medical record data. These data offer the potential to do high-quality, low-cost, rapid trials. Third, we must measure a wide range of meaningful outcomes. We should examine the effect of interventions on health care costs, health care utilization and health outcomes.”

Next steps could be focused on thinking about the key priority areas and how can experiments be used to generate new knowledge on what works and what does not. “Luckily, the complex world of health care provides endless opportunities for rapid-cycle, randomized trials that target health care costs and outcomes,” Dr. Patel said.
 

Reference

1. Oakes AH, Patel MS. A nudge towards increased experimentation to more rapidly improve healthcare. BMJ Qual Saf. 2020;29:179-181. doi: 10.1136/bmjqs-2019-009948. Accessed Dec 3, 2019.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Rheumatologists can look forward to the likely regulatory approval of the oral Janus kinase inhibitors tofacitinib and upadacitinib for the treatment of axial spondyloarthritis in the first half of 2021, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

This will be a major advance in the treatment of axial spondyloarthritis (axSpA) and promises to be one of the overall highlights of the coming year in rheumatology, according to the speakers. Both medications are now under Food and Drug Administration review for the proposed new indication.

“My sense is within the next 6 months we’re going to have two different oral JAK inhibitors that offer a new option for our ankylosing spondylitis and axial spondyloarthritis patients,” predicted Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.

Alexis R. Ogdie, MD, MSCE, noted that, at present, only two classes of potent medications are available for treatment of axial spondyloarthritis: tumor necrosis factor (TNF) inhibitors and anti–interleukin-17 biologics.

“I think it would be so exciting to have more treatment options. To have only two classes of drugs you can use for this disease is not enough,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

She and her fellow panelists also highlighted other recent key developments in axSpA, including epidemiologic evidence that case numbers are climbing sharply, identification of two previously unrecognized common comorbidities, a successful biologic remission induction and maintenance dose–reduction strategy, data on the best and worst biologics for patients with anterior uveitis, and evidence regarding next-step therapy in axSpA patients who’ve had an inadequate response to a TNF inhibitor.
 

The JAK inhibitors are coming

Oral tofacitinib (Xeljanz) at 5 mg twice daily was the focus of a pivotal phase 3, double-blind, 16-week, placebo-controlled clinical trial including 269 patients with axSpA. The results were presented at the 2020 annual meeting of the American College of Rheumatology. The primary endpoint was at least a 20% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 20). This was accomplished in 56.4% of patients on tofacitinib and 29.4% of placebo-treated controls. The ASAS 40 response rate was even more impressive: 40.6% with the JAK inhibitor, compared with 12.5% with placebo. There was one serious infection in the tofacitinib group, but no cases of venous thromboembolism, interstitial lung disease, opportunistic infection, major adverse cardiovascular events, or malignancy in this brief 4-month study.

Also now under FDA review are data from SELECT-AXIS 1, a phase 2/3, double-blind trial in which 187 biologic-naive patients with ankylosing spondylitis were randomized to 14 weeks of upadacitinib (Rinvoq) at 15 mg once daily or placebo. The primary endpoint, an ASAS 40 response, occurred in 51.6% of patients on the JAK inhibitor and half as many controls.

“They saw improvement in MRI scores with upadacitinib, so there’s biologic plausibility to this,” Dr. Ruderman noted.

He predicted the JAK inhibitors are going to have a big impact in clinical practice, especially in men.

“I have a lot of ankylosing spondylitis and axial spondyloarthritis patients on NSAIDs who I’m not convinced are doing as well as they could, but they push back every time I raise the possibility of going on a biologic,” the rheumatologist said. “I suspect that, given the rapid response with JAK inhibitors here, as in rheumatoid arthritis, it might be a little bit easier to persuade these people to give this a try for 4-6 weeks and then see how much better they are. It’s a pill. You don’t have to give yourself a shot.”

Dr. Ogdie predicted the new oral agents will bring more axSpA patients into rheumatologists’ offices.

“I think it’ll be kind of like the apremilast effect in psoriasis, where the drug got a lot more people into the market,” she said.

U.S. ankylosing spondylitis prevalence rising

The diagnostic prevalence of axSpA in the United States increased by 86% between 2006 and 2014 in a retrospective analysis based on Medicare fee-for-service claims data. A separate analysis using IBM MarketScan data for the same years was confirmatory, showing a 56% increase, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham reported at the 2020 annual meeting of the European League Against Rheumatism (EULAR), now known as the European Alliance of Associations for Rheumatology.

“I think the take home is we’re seeing more of this. Some of this is likely due to increased awareness and inclusion of nonradiographic disease,” according to Dr. Ruderman.
 

Two previously overlooked comorbidities

It’s well recognized that 5%-10% of patients with axSpA have concurrent inflammatory bowel disease. But how about irritable bowel syndrome (IBS)?

A study of 186 Swedish patients with axSpA in the population-based SPARTAKUS registry, none with inflammatory bowel disease, concluded that 30% of them met ROME III diagnostic criteria for IBS, compared with 16% of healthy controls. Of note, the axSpA patients with comorbid IBS had significantly worse axSpA disease outcomes, compared with those without IBS as measured by pain, fatigue, and quality-of-life scores, as well as significantly greater disease activity on the Bath Ankylosing Spondylitis Disease Activity Index.

New-onset inflammatory back pain occurred in a hefty 24% of 513 Saudi patients placed on isotretinoin for acne. About 42% of those with inflammatory back pain displayed evidence of sacroiliitis on MRI. Moreover, 52% of patients with MRI-proven sacroiliitis fulfilled ASAS criteria for axSpA. In this longitudinal study, the MRI abnormalities and back pain symptoms completely resolved after isotretinoin discontinuation, but it took a long time: up to 9 months.

“When you see these people with inflammatory back pain on isotretinoin, I think it’s important that before you saddle them with a diagnosis that they have axSpA – a diagnosis that will go with them forever – give them time off drug, because this can look like the real thing. It’s something to think about as these pretty young kids come in to see you with back pain: Always ask about their medication history because it could be important,” Dr. Ruderman said.

A successful biologic remission induction-and-maintenance strategy

The phase 3b, multicenter C-OPTIMISE study sought to determine the best strategy for avoiding axSpA flares once sustained clinical remission has been achieved with a TNF inhibitor, in this case certolizumab pegol (Cimzia). The first part of the trial involved 736 patients with early axSpA, including 329 with nonradiographic disease. During the 48-week open-label induction period, 43.9% of patients achieved sustained clinical remission at the approved dose of 200 mg every 2 weeks, with similar success rates in radiographic and nonradiographic axSpA.

Those in sustained remission were then randomized double blind to one of three groups: an additional 48 weeks of certolizumab pegol at the full maintenance dose of 200 mg every 2 weeks, reduced maintenance dosing at 200 mg every 4 weeks, or placebo. During this period, 83.7% of the group who continued on full-dose certolizumab remained flare free, as did 79% of those on the reduced maintenance dose. In contrast, only 20.2% of patients in whom the biologic was completely withdrawn remained flare free. The investigators concluded that certolizumab dose reduction is a winning strategy for maintenance of clinical remission, as it reduces costs and limits long-term exposure to immunosuppressive therapy while maintaining clinical benefits.
 

All biologics aren’t equal when it comes to anterior uveitis risk

An analysis of Swedish Rheumatology Quality Register data presented at the 2020 EULAR meeting concluded that, among 3,568 patients started on one of four biologics for treatment of spondyloarthritis, the incidence of anterior uveitis was 2.9 per 100 patient-years in those on infliximab (Remicade), 4.0 per 100 patient-years with adalimumab (Humira), 6.8 per 100 patient-years with secukinumab (Cosentyx), and 7.5 per 100 patient-years with etanercept (Enbrel).

Bruce Jancin/MDedge News

“This is important information for us in the clinic. The big question has been, do we see a reduced risk of anterior uveitis with secukinumab, an interleukin-17 inhibitor,” observed RWCS director Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

“When I’ve switched people with uveitis to secukinumab or ixekizumab [Taltz], I do see it come back. So I think it’s important to have these data out there,” Dr. Ogdie said.

Certolizumab pegol markedly reduced the incidence of anterior uveitis flares in patients with radiographic and nonradiographic axSpA and a history of recurrent uveitis flares in the ongoing phase 4 C-VIEW study. In the 48 weeks prior to going on certolizumab pegol, the 89 participants included in this analysis had an acute anterior uveitis incidence of 1.5 episodes per patient; during their first 48 weeks on the TNF inhibitor, the rate plunged to 0.2 episodes, representing an 87% reduction.
 

Secukinumab ‘not the obvious choice’ after inadequate response to a TNF inhibitor

While it might seem logical to turn to an IL-17 inhibitor in patients with an inadequate response to one or more TNF inhibitors, two recently published studies suggest that starting secukinumab is not more effective than trying yet another TNF inhibitor.

A retrospective analysis of Swiss registry data on next-step therapy in 390 axSpA patients who had withdrawn from one or more TNF inhibitors concluded that efficacy at 1 year in the 106 who switched to secukinumab wasn’t significantly different than in the 284 who moved on to another TNF inhibitor.

Similarly, an analysis of 10,583 courses of biologic therapy in 8,050 axSpA patients in five Nordic registries concluded that secukinumab and adalimumab as second-line therapy in patients with inadequate response to an initial TNF inhibitor performed similarly through 1 year of follow-up. However, in patients who’d previously failed to respond to two or three different biologic agents, adalimumab proved superior to the interleukin-17 inhibitor.

“These are two studies that don’t support the intuitive notion of trying a drug with a different mechanism of action when a patient has an inadequate response to a TNF inhibitor. It’s not clear that’s going to make a difference. It doesn’t mean secukinumab can’t work, but it means secukinumab is not the obvious choice,” Dr. Ruderman commented.

All three speakers reported financial relationships with numerous pharmaceutical companies.

[email protected]

Rheumatologists can look forward to the likely regulatory approval of the oral Janus kinase inhibitors tofacitinib and upadacitinib for the treatment of axial spondyloarthritis in the first half of 2021, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

This will be a major advance in the treatment of axial spondyloarthritis (axSpA) and promises to be one of the overall highlights of the coming year in rheumatology, according to the speakers. Both medications are now under Food and Drug Administration review for the proposed new indication.

“My sense is within the next 6 months we’re going to have two different oral JAK inhibitors that offer a new option for our ankylosing spondylitis and axial spondyloarthritis patients,” predicted Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.

Alexis R. Ogdie, MD, MSCE, noted that, at present, only two classes of potent medications are available for treatment of axial spondyloarthritis: tumor necrosis factor (TNF) inhibitors and anti–interleukin-17 biologics.

“I think it would be so exciting to have more treatment options. To have only two classes of drugs you can use for this disease is not enough,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

She and her fellow panelists also highlighted other recent key developments in axSpA, including epidemiologic evidence that case numbers are climbing sharply, identification of two previously unrecognized common comorbidities, a successful biologic remission induction and maintenance dose–reduction strategy, data on the best and worst biologics for patients with anterior uveitis, and evidence regarding next-step therapy in axSpA patients who’ve had an inadequate response to a TNF inhibitor.
 

The JAK inhibitors are coming

Oral tofacitinib (Xeljanz) at 5 mg twice daily was the focus of a pivotal phase 3, double-blind, 16-week, placebo-controlled clinical trial including 269 patients with axSpA. The results were presented at the 2020 annual meeting of the American College of Rheumatology. The primary endpoint was at least a 20% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 20). This was accomplished in 56.4% of patients on tofacitinib and 29.4% of placebo-treated controls. The ASAS 40 response rate was even more impressive: 40.6% with the JAK inhibitor, compared with 12.5% with placebo. There was one serious infection in the tofacitinib group, but no cases of venous thromboembolism, interstitial lung disease, opportunistic infection, major adverse cardiovascular events, or malignancy in this brief 4-month study.

Also now under FDA review are data from SELECT-AXIS 1, a phase 2/3, double-blind trial in which 187 biologic-naive patients with ankylosing spondylitis were randomized to 14 weeks of upadacitinib (Rinvoq) at 15 mg once daily or placebo. The primary endpoint, an ASAS 40 response, occurred in 51.6% of patients on the JAK inhibitor and half as many controls.

“They saw improvement in MRI scores with upadacitinib, so there’s biologic plausibility to this,” Dr. Ruderman noted.

He predicted the JAK inhibitors are going to have a big impact in clinical practice, especially in men.

“I have a lot of ankylosing spondylitis and axial spondyloarthritis patients on NSAIDs who I’m not convinced are doing as well as they could, but they push back every time I raise the possibility of going on a biologic,” the rheumatologist said. “I suspect that, given the rapid response with JAK inhibitors here, as in rheumatoid arthritis, it might be a little bit easier to persuade these people to give this a try for 4-6 weeks and then see how much better they are. It’s a pill. You don’t have to give yourself a shot.”

Dr. Ogdie predicted the new oral agents will bring more axSpA patients into rheumatologists’ offices.

“I think it’ll be kind of like the apremilast effect in psoriasis, where the drug got a lot more people into the market,” she said.

U.S. ankylosing spondylitis prevalence rising

The diagnostic prevalence of axSpA in the United States increased by 86% between 2006 and 2014 in a retrospective analysis based on Medicare fee-for-service claims data. A separate analysis using IBM MarketScan data for the same years was confirmatory, showing a 56% increase, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham reported at the 2020 annual meeting of the European League Against Rheumatism (EULAR), now known as the European Alliance of Associations for Rheumatology.

“I think the take home is we’re seeing more of this. Some of this is likely due to increased awareness and inclusion of nonradiographic disease,” according to Dr. Ruderman.
 

Two previously overlooked comorbidities

It’s well recognized that 5%-10% of patients with axSpA have concurrent inflammatory bowel disease. But how about irritable bowel syndrome (IBS)?

A study of 186 Swedish patients with axSpA in the population-based SPARTAKUS registry, none with inflammatory bowel disease, concluded that 30% of them met ROME III diagnostic criteria for IBS, compared with 16% of healthy controls. Of note, the axSpA patients with comorbid IBS had significantly worse axSpA disease outcomes, compared with those without IBS as measured by pain, fatigue, and quality-of-life scores, as well as significantly greater disease activity on the Bath Ankylosing Spondylitis Disease Activity Index.

New-onset inflammatory back pain occurred in a hefty 24% of 513 Saudi patients placed on isotretinoin for acne. About 42% of those with inflammatory back pain displayed evidence of sacroiliitis on MRI. Moreover, 52% of patients with MRI-proven sacroiliitis fulfilled ASAS criteria for axSpA. In this longitudinal study, the MRI abnormalities and back pain symptoms completely resolved after isotretinoin discontinuation, but it took a long time: up to 9 months.

“When you see these people with inflammatory back pain on isotretinoin, I think it’s important that before you saddle them with a diagnosis that they have axSpA – a diagnosis that will go with them forever – give them time off drug, because this can look like the real thing. It’s something to think about as these pretty young kids come in to see you with back pain: Always ask about their medication history because it could be important,” Dr. Ruderman said.

A successful biologic remission induction-and-maintenance strategy

The phase 3b, multicenter C-OPTIMISE study sought to determine the best strategy for avoiding axSpA flares once sustained clinical remission has been achieved with a TNF inhibitor, in this case certolizumab pegol (Cimzia). The first part of the trial involved 736 patients with early axSpA, including 329 with nonradiographic disease. During the 48-week open-label induction period, 43.9% of patients achieved sustained clinical remission at the approved dose of 200 mg every 2 weeks, with similar success rates in radiographic and nonradiographic axSpA.

Those in sustained remission were then randomized double blind to one of three groups: an additional 48 weeks of certolizumab pegol at the full maintenance dose of 200 mg every 2 weeks, reduced maintenance dosing at 200 mg every 4 weeks, or placebo. During this period, 83.7% of the group who continued on full-dose certolizumab remained flare free, as did 79% of those on the reduced maintenance dose. In contrast, only 20.2% of patients in whom the biologic was completely withdrawn remained flare free. The investigators concluded that certolizumab dose reduction is a winning strategy for maintenance of clinical remission, as it reduces costs and limits long-term exposure to immunosuppressive therapy while maintaining clinical benefits.
 

All biologics aren’t equal when it comes to anterior uveitis risk

An analysis of Swedish Rheumatology Quality Register data presented at the 2020 EULAR meeting concluded that, among 3,568 patients started on one of four biologics for treatment of spondyloarthritis, the incidence of anterior uveitis was 2.9 per 100 patient-years in those on infliximab (Remicade), 4.0 per 100 patient-years with adalimumab (Humira), 6.8 per 100 patient-years with secukinumab (Cosentyx), and 7.5 per 100 patient-years with etanercept (Enbrel).

Bruce Jancin/MDedge News

“This is important information for us in the clinic. The big question has been, do we see a reduced risk of anterior uveitis with secukinumab, an interleukin-17 inhibitor,” observed RWCS director Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

“When I’ve switched people with uveitis to secukinumab or ixekizumab [Taltz], I do see it come back. So I think it’s important to have these data out there,” Dr. Ogdie said.

Certolizumab pegol markedly reduced the incidence of anterior uveitis flares in patients with radiographic and nonradiographic axSpA and a history of recurrent uveitis flares in the ongoing phase 4 C-VIEW study. In the 48 weeks prior to going on certolizumab pegol, the 89 participants included in this analysis had an acute anterior uveitis incidence of 1.5 episodes per patient; during their first 48 weeks on the TNF inhibitor, the rate plunged to 0.2 episodes, representing an 87% reduction.
 

Secukinumab ‘not the obvious choice’ after inadequate response to a TNF inhibitor

While it might seem logical to turn to an IL-17 inhibitor in patients with an inadequate response to one or more TNF inhibitors, two recently published studies suggest that starting secukinumab is not more effective than trying yet another TNF inhibitor.

A retrospective analysis of Swiss registry data on next-step therapy in 390 axSpA patients who had withdrawn from one or more TNF inhibitors concluded that efficacy at 1 year in the 106 who switched to secukinumab wasn’t significantly different than in the 284 who moved on to another TNF inhibitor.

Similarly, an analysis of 10,583 courses of biologic therapy in 8,050 axSpA patients in five Nordic registries concluded that secukinumab and adalimumab as second-line therapy in patients with inadequate response to an initial TNF inhibitor performed similarly through 1 year of follow-up. However, in patients who’d previously failed to respond to two or three different biologic agents, adalimumab proved superior to the interleukin-17 inhibitor.

“These are two studies that don’t support the intuitive notion of trying a drug with a different mechanism of action when a patient has an inadequate response to a TNF inhibitor. It’s not clear that’s going to make a difference. It doesn’t mean secukinumab can’t work, but it means secukinumab is not the obvious choice,” Dr. Ruderman commented.

All three speakers reported financial relationships with numerous pharmaceutical companies.

[email protected]

Rheumatologists can look forward to the likely regulatory approval of the oral Janus kinase inhibitors tofacitinib and upadacitinib for the treatment of axial spondyloarthritis in the first half of 2021, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

This will be a major advance in the treatment of axial spondyloarthritis (axSpA) and promises to be one of the overall highlights of the coming year in rheumatology, according to the speakers. Both medications are now under Food and Drug Administration review for the proposed new indication.

“My sense is within the next 6 months we’re going to have two different oral JAK inhibitors that offer a new option for our ankylosing spondylitis and axial spondyloarthritis patients,” predicted Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.

Alexis R. Ogdie, MD, MSCE, noted that, at present, only two classes of potent medications are available for treatment of axial spondyloarthritis: tumor necrosis factor (TNF) inhibitors and anti–interleukin-17 biologics.

“I think it would be so exciting to have more treatment options. To have only two classes of drugs you can use for this disease is not enough,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

She and her fellow panelists also highlighted other recent key developments in axSpA, including epidemiologic evidence that case numbers are climbing sharply, identification of two previously unrecognized common comorbidities, a successful biologic remission induction and maintenance dose–reduction strategy, data on the best and worst biologics for patients with anterior uveitis, and evidence regarding next-step therapy in axSpA patients who’ve had an inadequate response to a TNF inhibitor.
 

The JAK inhibitors are coming

Oral tofacitinib (Xeljanz) at 5 mg twice daily was the focus of a pivotal phase 3, double-blind, 16-week, placebo-controlled clinical trial including 269 patients with axSpA. The results were presented at the 2020 annual meeting of the American College of Rheumatology. The primary endpoint was at least a 20% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 20). This was accomplished in 56.4% of patients on tofacitinib and 29.4% of placebo-treated controls. The ASAS 40 response rate was even more impressive: 40.6% with the JAK inhibitor, compared with 12.5% with placebo. There was one serious infection in the tofacitinib group, but no cases of venous thromboembolism, interstitial lung disease, opportunistic infection, major adverse cardiovascular events, or malignancy in this brief 4-month study.

Also now under FDA review are data from SELECT-AXIS 1, a phase 2/3, double-blind trial in which 187 biologic-naive patients with ankylosing spondylitis were randomized to 14 weeks of upadacitinib (Rinvoq) at 15 mg once daily or placebo. The primary endpoint, an ASAS 40 response, occurred in 51.6% of patients on the JAK inhibitor and half as many controls.

“They saw improvement in MRI scores with upadacitinib, so there’s biologic plausibility to this,” Dr. Ruderman noted.

He predicted the JAK inhibitors are going to have a big impact in clinical practice, especially in men.

“I have a lot of ankylosing spondylitis and axial spondyloarthritis patients on NSAIDs who I’m not convinced are doing as well as they could, but they push back every time I raise the possibility of going on a biologic,” the rheumatologist said. “I suspect that, given the rapid response with JAK inhibitors here, as in rheumatoid arthritis, it might be a little bit easier to persuade these people to give this a try for 4-6 weeks and then see how much better they are. It’s a pill. You don’t have to give yourself a shot.”

Dr. Ogdie predicted the new oral agents will bring more axSpA patients into rheumatologists’ offices.

“I think it’ll be kind of like the apremilast effect in psoriasis, where the drug got a lot more people into the market,” she said.

U.S. ankylosing spondylitis prevalence rising

The diagnostic prevalence of axSpA in the United States increased by 86% between 2006 and 2014 in a retrospective analysis based on Medicare fee-for-service claims data. A separate analysis using IBM MarketScan data for the same years was confirmatory, showing a 56% increase, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham reported at the 2020 annual meeting of the European League Against Rheumatism (EULAR), now known as the European Alliance of Associations for Rheumatology.

“I think the take home is we’re seeing more of this. Some of this is likely due to increased awareness and inclusion of nonradiographic disease,” according to Dr. Ruderman.
 

Two previously overlooked comorbidities

It’s well recognized that 5%-10% of patients with axSpA have concurrent inflammatory bowel disease. But how about irritable bowel syndrome (IBS)?

A study of 186 Swedish patients with axSpA in the population-based SPARTAKUS registry, none with inflammatory bowel disease, concluded that 30% of them met ROME III diagnostic criteria for IBS, compared with 16% of healthy controls. Of note, the axSpA patients with comorbid IBS had significantly worse axSpA disease outcomes, compared with those without IBS as measured by pain, fatigue, and quality-of-life scores, as well as significantly greater disease activity on the Bath Ankylosing Spondylitis Disease Activity Index.

New-onset inflammatory back pain occurred in a hefty 24% of 513 Saudi patients placed on isotretinoin for acne. About 42% of those with inflammatory back pain displayed evidence of sacroiliitis on MRI. Moreover, 52% of patients with MRI-proven sacroiliitis fulfilled ASAS criteria for axSpA. In this longitudinal study, the MRI abnormalities and back pain symptoms completely resolved after isotretinoin discontinuation, but it took a long time: up to 9 months.

“When you see these people with inflammatory back pain on isotretinoin, I think it’s important that before you saddle them with a diagnosis that they have axSpA – a diagnosis that will go with them forever – give them time off drug, because this can look like the real thing. It’s something to think about as these pretty young kids come in to see you with back pain: Always ask about their medication history because it could be important,” Dr. Ruderman said.

A successful biologic remission induction-and-maintenance strategy

The phase 3b, multicenter C-OPTIMISE study sought to determine the best strategy for avoiding axSpA flares once sustained clinical remission has been achieved with a TNF inhibitor, in this case certolizumab pegol (Cimzia). The first part of the trial involved 736 patients with early axSpA, including 329 with nonradiographic disease. During the 48-week open-label induction period, 43.9% of patients achieved sustained clinical remission at the approved dose of 200 mg every 2 weeks, with similar success rates in radiographic and nonradiographic axSpA.

Those in sustained remission were then randomized double blind to one of three groups: an additional 48 weeks of certolizumab pegol at the full maintenance dose of 200 mg every 2 weeks, reduced maintenance dosing at 200 mg every 4 weeks, or placebo. During this period, 83.7% of the group who continued on full-dose certolizumab remained flare free, as did 79% of those on the reduced maintenance dose. In contrast, only 20.2% of patients in whom the biologic was completely withdrawn remained flare free. The investigators concluded that certolizumab dose reduction is a winning strategy for maintenance of clinical remission, as it reduces costs and limits long-term exposure to immunosuppressive therapy while maintaining clinical benefits.
 

All biologics aren’t equal when it comes to anterior uveitis risk

An analysis of Swedish Rheumatology Quality Register data presented at the 2020 EULAR meeting concluded that, among 3,568 patients started on one of four biologics for treatment of spondyloarthritis, the incidence of anterior uveitis was 2.9 per 100 patient-years in those on infliximab (Remicade), 4.0 per 100 patient-years with adalimumab (Humira), 6.8 per 100 patient-years with secukinumab (Cosentyx), and 7.5 per 100 patient-years with etanercept (Enbrel).

Bruce Jancin/MDedge News

“This is important information for us in the clinic. The big question has been, do we see a reduced risk of anterior uveitis with secukinumab, an interleukin-17 inhibitor,” observed RWCS director Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.

“When I’ve switched people with uveitis to secukinumab or ixekizumab [Taltz], I do see it come back. So I think it’s important to have these data out there,” Dr. Ogdie said.

Certolizumab pegol markedly reduced the incidence of anterior uveitis flares in patients with radiographic and nonradiographic axSpA and a history of recurrent uveitis flares in the ongoing phase 4 C-VIEW study. In the 48 weeks prior to going on certolizumab pegol, the 89 participants included in this analysis had an acute anterior uveitis incidence of 1.5 episodes per patient; during their first 48 weeks on the TNF inhibitor, the rate plunged to 0.2 episodes, representing an 87% reduction.
 

Secukinumab ‘not the obvious choice’ after inadequate response to a TNF inhibitor

While it might seem logical to turn to an IL-17 inhibitor in patients with an inadequate response to one or more TNF inhibitors, two recently published studies suggest that starting secukinumab is not more effective than trying yet another TNF inhibitor.

A retrospective analysis of Swiss registry data on next-step therapy in 390 axSpA patients who had withdrawn from one or more TNF inhibitors concluded that efficacy at 1 year in the 106 who switched to secukinumab wasn’t significantly different than in the 284 who moved on to another TNF inhibitor.

Similarly, an analysis of 10,583 courses of biologic therapy in 8,050 axSpA patients in five Nordic registries concluded that secukinumab and adalimumab as second-line therapy in patients with inadequate response to an initial TNF inhibitor performed similarly through 1 year of follow-up. However, in patients who’d previously failed to respond to two or three different biologic agents, adalimumab proved superior to the interleukin-17 inhibitor.

“These are two studies that don’t support the intuitive notion of trying a drug with a different mechanism of action when a patient has an inadequate response to a TNF inhibitor. It’s not clear that’s going to make a difference. It doesn’t mean secukinumab can’t work, but it means secukinumab is not the obvious choice,” Dr. Ruderman commented.

All three speakers reported financial relationships with numerous pharmaceutical companies.

[email protected]

With the daily stream of new information, it is difficult to keep up with data on how the coronavirus epidemic affects children and school attendance, as well as how pediatricians can advise parents. The following is a summary of recently published information about birth and infant outcomes, and symptoms seen in infants and children, along with a review of recent information on transmission in schools.

COVID-19 in newborns

In November 2020, the Centers for Disease Control and Prevention published data from 16 jurisdictions detailing pregnancy and infant outcomes of more than 5,000 women with SARS-CoV-2 infection. The data were collected from March to October 2020. More than 80% of the women found to be positive for SARS-CoV-2 were identified during their third trimester. The surveillance found that 12.9% of infants born to infected mothers were born preterm, compared with an expected rate in the population of approximately 10%, suggesting that third-trimester infection may be associated with an increase in premature birth. Among 610 infants born to infected mothers and tested for SARS-CoV-2 during their nursery stay, 2.6% were positive. The infant positivity rate was as high as 4.3% among infants who were born to women with a documented SARS-CoV-2 infection within 2 weeks of the delivery date. No newborn infections were found among the infants whose mothers’ infection occurred more than 14 days before delivery. Current CDC and American Academy of Pediatrics recommendations are to test infants born to mothers with suspected or confirmed SARS-CoV-2 infection.

Data on clinical characteristics of a series of hospitalized infants in Montreal was published in December 2020. The study identified infants 0-12 months old who were diagnosed or treated at a single Montreal hospital from February until May 2020. In all, 25 (2.0%) of 1,165 infants were confirmed to have SARS-CoV-2, and approximately 8 of those were hospitalized; 85% had gastrointestinal symptoms and 81% had a fever. Upper respiratory tract symptoms were present in 59%, and none of the hospitalized infants required supplemental oxygen. The data overall support the idea that infants are generally only mildly symptomatic when infected, and respiratory symptoms do not appear to be the most prevalent finding.
 

COVID-19 in children

The lack of prominent respiratory symptoms among children with SARS-CoV-2 infection symptoms was echoed in another study that evaluated more than 2,400 children in Alberta, Canada. Among the 1,987 children who tested positive for SARS-CoV-2, one-third (35.9%) were asymptomatic. Some symptoms were not helpful in differentiating children who tested positive vs. those who tested negative. The frequency of muscle or joint pain, myalgia, malaise, and respiratory symptoms such as nasal congestion, difficulty breathing, and sore throat was indistinguishable between the SARS-CoV-2–infected and –noninfected children. However, anosmia was much more prevalent (7.7%) among those who tested positive for SARS-CoV-2, compared with 1.1% of those who were negative. Headache was present in 15.7% of those who were positive vs. 6.3% of those who were negative. Fever was slightly more prevalent, at 25.5% among the positive patients and 15% of the negative patients.

The authors calculated likelihood ratios for individual symptoms and found that almost all individual symptoms had likelihood ratios of 1:1.8 for testing positive. However, nausea and vomiting had a likelihood ratio of 5.5, and for anosmia it was 7.3. The combination of symptoms of nausea, nausea and vomiting, and headache produced a likelihood ratio of nearly 66. The authors suggest that these data on ambulatory children indicate that, in general, respiratory symptoms are not helpful for distinguishing patients who are likely to be positive, although the symptoms of nausea, headache, and both along with fever can be highly predictive. The authors propose that it may be more helpful for schools to focus on identifying children with combinations of these high-yield symptoms for potential testing and exclusion from school rather than on random or isolated respiratory symptoms.
 

COVID-19 in schools

Transmission risk in different settings is certainly something parents quiz pediatricians about, so data released in January and February 2021 may help provide some context. A CDC report on the experience of 17 schools in Wisconsin from August to November 2020 is illuminating. In that study, the SARS-CoV-2 case rate in students, school teachers, and staff members was 63% of the rate in the general public at the time, suggesting that the mitigation strategies used by the schools were effective. In addition, among the students who contracted SARS-CoV-2, only 5% of cases were attributable to school exposure. No cases of SARS-CoV-2 among faculty or staff were linked to school exposure.

Indeed, data released on Feb. 2, 2021, demonstrate that younger adults are the largest source of sustaining the epidemic. On the basis of data from August to October 2020, the opening of schools does not appear to be associated with population-level changes in SARS-CoV-2–attributable deaths. For October 2020, the authors estimate that 2.7% of infections were from children 0-9 years old, 7.1% from those ages 10-19 years, but 34% from those 20-34 years old and 38% from those 35-49 years old, by far the largest two groups contributing to spread. It should be noted that ages 20-49 years are the peak working years for adults, but the source of the data did not allow the authors to conclude whether infections were work related or social activity related. Their data do suggest that prioritizing vaccination of younger working-age adults may put more of a dent in the pandemic spread than vaccinating older individuals.

In a similar vein, a systematic review and meta-analysis of recent studies looked at household transmission of SARS-CoV-2 and demonstrated an attack rate within households of 16.6%. Of note, secondary household attack rates were only 0.7% from asymptomatic cases and 18% from symptomatic cases, with spouses and adult household contacts having higher secondary attack rates than children in the household.
 

COVID-19 in student athletes

A recent MMWR report described a SARS-CoV-2 outbreak associated with a series of wrestling tournaments in Florida, held in December and January 2021. While everyone would like children to be able to participate in sports, such events potentially violate several of the precepts for preventing spread: Avoid close contact and don’t mix contacts from different schools. Moreover, the events occurred during some of the highest incident case rates in the counties where the tournaments took place.

On Dec. 4, 2020, the AAP released updated guidance for athletic activities and recommended cloth face coverings for student athletes during training, in competition, while traveling, and even while waiting on the sidelines and not actively playing. Notable exceptions to the recommendation were competitive cheerleading, gymnastics, wrestling, and water sports, where the risk for entanglement from face coverings was too high or was not practical.

Taken as a whole, the evolving data continue to show that school mitigation practices can be effective in reducing the risk for SARS-CoV-2 infection. In addition, SARS-CoV-2 rates among schoolchildren more closely mirror community rates and are probably more influenced by what happens outside the schools than inside the schools.

A version of this article first appeared on Medscape.com.

With the daily stream of new information, it is difficult to keep up with data on how the coronavirus epidemic affects children and school attendance, as well as how pediatricians can advise parents. The following is a summary of recently published information about birth and infant outcomes, and symptoms seen in infants and children, along with a review of recent information on transmission in schools.

COVID-19 in newborns

In November 2020, the Centers for Disease Control and Prevention published data from 16 jurisdictions detailing pregnancy and infant outcomes of more than 5,000 women with SARS-CoV-2 infection. The data were collected from March to October 2020. More than 80% of the women found to be positive for SARS-CoV-2 were identified during their third trimester. The surveillance found that 12.9% of infants born to infected mothers were born preterm, compared with an expected rate in the population of approximately 10%, suggesting that third-trimester infection may be associated with an increase in premature birth. Among 610 infants born to infected mothers and tested for SARS-CoV-2 during their nursery stay, 2.6% were positive. The infant positivity rate was as high as 4.3% among infants who were born to women with a documented SARS-CoV-2 infection within 2 weeks of the delivery date. No newborn infections were found among the infants whose mothers’ infection occurred more than 14 days before delivery. Current CDC and American Academy of Pediatrics recommendations are to test infants born to mothers with suspected or confirmed SARS-CoV-2 infection.

Data on clinical characteristics of a series of hospitalized infants in Montreal was published in December 2020. The study identified infants 0-12 months old who were diagnosed or treated at a single Montreal hospital from February until May 2020. In all, 25 (2.0%) of 1,165 infants were confirmed to have SARS-CoV-2, and approximately 8 of those were hospitalized; 85% had gastrointestinal symptoms and 81% had a fever. Upper respiratory tract symptoms were present in 59%, and none of the hospitalized infants required supplemental oxygen. The data overall support the idea that infants are generally only mildly symptomatic when infected, and respiratory symptoms do not appear to be the most prevalent finding.
 

COVID-19 in children

The lack of prominent respiratory symptoms among children with SARS-CoV-2 infection symptoms was echoed in another study that evaluated more than 2,400 children in Alberta, Canada. Among the 1,987 children who tested positive for SARS-CoV-2, one-third (35.9%) were asymptomatic. Some symptoms were not helpful in differentiating children who tested positive vs. those who tested negative. The frequency of muscle or joint pain, myalgia, malaise, and respiratory symptoms such as nasal congestion, difficulty breathing, and sore throat was indistinguishable between the SARS-CoV-2–infected and –noninfected children. However, anosmia was much more prevalent (7.7%) among those who tested positive for SARS-CoV-2, compared with 1.1% of those who were negative. Headache was present in 15.7% of those who were positive vs. 6.3% of those who were negative. Fever was slightly more prevalent, at 25.5% among the positive patients and 15% of the negative patients.

The authors calculated likelihood ratios for individual symptoms and found that almost all individual symptoms had likelihood ratios of 1:1.8 for testing positive. However, nausea and vomiting had a likelihood ratio of 5.5, and for anosmia it was 7.3. The combination of symptoms of nausea, nausea and vomiting, and headache produced a likelihood ratio of nearly 66. The authors suggest that these data on ambulatory children indicate that, in general, respiratory symptoms are not helpful for distinguishing patients who are likely to be positive, although the symptoms of nausea, headache, and both along with fever can be highly predictive. The authors propose that it may be more helpful for schools to focus on identifying children with combinations of these high-yield symptoms for potential testing and exclusion from school rather than on random or isolated respiratory symptoms.
 

COVID-19 in schools

Transmission risk in different settings is certainly something parents quiz pediatricians about, so data released in January and February 2021 may help provide some context. A CDC report on the experience of 17 schools in Wisconsin from August to November 2020 is illuminating. In that study, the SARS-CoV-2 case rate in students, school teachers, and staff members was 63% of the rate in the general public at the time, suggesting that the mitigation strategies used by the schools were effective. In addition, among the students who contracted SARS-CoV-2, only 5% of cases were attributable to school exposure. No cases of SARS-CoV-2 among faculty or staff were linked to school exposure.

Indeed, data released on Feb. 2, 2021, demonstrate that younger adults are the largest source of sustaining the epidemic. On the basis of data from August to October 2020, the opening of schools does not appear to be associated with population-level changes in SARS-CoV-2–attributable deaths. For October 2020, the authors estimate that 2.7% of infections were from children 0-9 years old, 7.1% from those ages 10-19 years, but 34% from those 20-34 years old and 38% from those 35-49 years old, by far the largest two groups contributing to spread. It should be noted that ages 20-49 years are the peak working years for adults, but the source of the data did not allow the authors to conclude whether infections were work related or social activity related. Their data do suggest that prioritizing vaccination of younger working-age adults may put more of a dent in the pandemic spread than vaccinating older individuals.

In a similar vein, a systematic review and meta-analysis of recent studies looked at household transmission of SARS-CoV-2 and demonstrated an attack rate within households of 16.6%. Of note, secondary household attack rates were only 0.7% from asymptomatic cases and 18% from symptomatic cases, with spouses and adult household contacts having higher secondary attack rates than children in the household.
 

COVID-19 in student athletes

A recent MMWR report described a SARS-CoV-2 outbreak associated with a series of wrestling tournaments in Florida, held in December and January 2021. While everyone would like children to be able to participate in sports, such events potentially violate several of the precepts for preventing spread: Avoid close contact and don’t mix contacts from different schools. Moreover, the events occurred during some of the highest incident case rates in the counties where the tournaments took place.

On Dec. 4, 2020, the AAP released updated guidance for athletic activities and recommended cloth face coverings for student athletes during training, in competition, while traveling, and even while waiting on the sidelines and not actively playing. Notable exceptions to the recommendation were competitive cheerleading, gymnastics, wrestling, and water sports, where the risk for entanglement from face coverings was too high or was not practical.

Taken as a whole, the evolving data continue to show that school mitigation practices can be effective in reducing the risk for SARS-CoV-2 infection. In addition, SARS-CoV-2 rates among schoolchildren more closely mirror community rates and are probably more influenced by what happens outside the schools than inside the schools.

A version of this article first appeared on Medscape.com.

With the daily stream of new information, it is difficult to keep up with data on how the coronavirus epidemic affects children and school attendance, as well as how pediatricians can advise parents. The following is a summary of recently published information about birth and infant outcomes, and symptoms seen in infants and children, along with a review of recent information on transmission in schools.

COVID-19 in newborns

In November 2020, the Centers for Disease Control and Prevention published data from 16 jurisdictions detailing pregnancy and infant outcomes of more than 5,000 women with SARS-CoV-2 infection. The data were collected from March to October 2020. More than 80% of the women found to be positive for SARS-CoV-2 were identified during their third trimester. The surveillance found that 12.9% of infants born to infected mothers were born preterm, compared with an expected rate in the population of approximately 10%, suggesting that third-trimester infection may be associated with an increase in premature birth. Among 610 infants born to infected mothers and tested for SARS-CoV-2 during their nursery stay, 2.6% were positive. The infant positivity rate was as high as 4.3% among infants who were born to women with a documented SARS-CoV-2 infection within 2 weeks of the delivery date. No newborn infections were found among the infants whose mothers’ infection occurred more than 14 days before delivery. Current CDC and American Academy of Pediatrics recommendations are to test infants born to mothers with suspected or confirmed SARS-CoV-2 infection.

Data on clinical characteristics of a series of hospitalized infants in Montreal was published in December 2020. The study identified infants 0-12 months old who were diagnosed or treated at a single Montreal hospital from February until May 2020. In all, 25 (2.0%) of 1,165 infants were confirmed to have SARS-CoV-2, and approximately 8 of those were hospitalized; 85% had gastrointestinal symptoms and 81% had a fever. Upper respiratory tract symptoms were present in 59%, and none of the hospitalized infants required supplemental oxygen. The data overall support the idea that infants are generally only mildly symptomatic when infected, and respiratory symptoms do not appear to be the most prevalent finding.
 

COVID-19 in children

The lack of prominent respiratory symptoms among children with SARS-CoV-2 infection symptoms was echoed in another study that evaluated more than 2,400 children in Alberta, Canada. Among the 1,987 children who tested positive for SARS-CoV-2, one-third (35.9%) were asymptomatic. Some symptoms were not helpful in differentiating children who tested positive vs. those who tested negative. The frequency of muscle or joint pain, myalgia, malaise, and respiratory symptoms such as nasal congestion, difficulty breathing, and sore throat was indistinguishable between the SARS-CoV-2–infected and –noninfected children. However, anosmia was much more prevalent (7.7%) among those who tested positive for SARS-CoV-2, compared with 1.1% of those who were negative. Headache was present in 15.7% of those who were positive vs. 6.3% of those who were negative. Fever was slightly more prevalent, at 25.5% among the positive patients and 15% of the negative patients.

The authors calculated likelihood ratios for individual symptoms and found that almost all individual symptoms had likelihood ratios of 1:1.8 for testing positive. However, nausea and vomiting had a likelihood ratio of 5.5, and for anosmia it was 7.3. The combination of symptoms of nausea, nausea and vomiting, and headache produced a likelihood ratio of nearly 66. The authors suggest that these data on ambulatory children indicate that, in general, respiratory symptoms are not helpful for distinguishing patients who are likely to be positive, although the symptoms of nausea, headache, and both along with fever can be highly predictive. The authors propose that it may be more helpful for schools to focus on identifying children with combinations of these high-yield symptoms for potential testing and exclusion from school rather than on random or isolated respiratory symptoms.
 

COVID-19 in schools

Transmission risk in different settings is certainly something parents quiz pediatricians about, so data released in January and February 2021 may help provide some context. A CDC report on the experience of 17 schools in Wisconsin from August to November 2020 is illuminating. In that study, the SARS-CoV-2 case rate in students, school teachers, and staff members was 63% of the rate in the general public at the time, suggesting that the mitigation strategies used by the schools were effective. In addition, among the students who contracted SARS-CoV-2, only 5% of cases were attributable to school exposure. No cases of SARS-CoV-2 among faculty or staff were linked to school exposure.

Indeed, data released on Feb. 2, 2021, demonstrate that younger adults are the largest source of sustaining the epidemic. On the basis of data from August to October 2020, the opening of schools does not appear to be associated with population-level changes in SARS-CoV-2–attributable deaths. For October 2020, the authors estimate that 2.7% of infections were from children 0-9 years old, 7.1% from those ages 10-19 years, but 34% from those 20-34 years old and 38% from those 35-49 years old, by far the largest two groups contributing to spread. It should be noted that ages 20-49 years are the peak working years for adults, but the source of the data did not allow the authors to conclude whether infections were work related or social activity related. Their data do suggest that prioritizing vaccination of younger working-age adults may put more of a dent in the pandemic spread than vaccinating older individuals.

In a similar vein, a systematic review and meta-analysis of recent studies looked at household transmission of SARS-CoV-2 and demonstrated an attack rate within households of 16.6%. Of note, secondary household attack rates were only 0.7% from asymptomatic cases and 18% from symptomatic cases, with spouses and adult household contacts having higher secondary attack rates than children in the household.
 

COVID-19 in student athletes

A recent MMWR report described a SARS-CoV-2 outbreak associated with a series of wrestling tournaments in Florida, held in December and January 2021. While everyone would like children to be able to participate in sports, such events potentially violate several of the precepts for preventing spread: Avoid close contact and don’t mix contacts from different schools. Moreover, the events occurred during some of the highest incident case rates in the counties where the tournaments took place.

On Dec. 4, 2020, the AAP released updated guidance for athletic activities and recommended cloth face coverings for student athletes during training, in competition, while traveling, and even while waiting on the sidelines and not actively playing. Notable exceptions to the recommendation were competitive cheerleading, gymnastics, wrestling, and water sports, where the risk for entanglement from face coverings was too high or was not practical.

Taken as a whole, the evolving data continue to show that school mitigation practices can be effective in reducing the risk for SARS-CoV-2 infection. In addition, SARS-CoV-2 rates among schoolchildren more closely mirror community rates and are probably more influenced by what happens outside the schools than inside the schools.

A version of this article first appeared on Medscape.com.

This patient had hand and foot psoriasis with the classic thick scale and erythema on his palms and soles. Additionally, in the area of the sole toward the heel, he had hyperpigmented macules called mahogany spots that are another hallmark of psoriasis. Pitting and distal onycholysis were also visible on his right ring finger.

This case illustrates how the painful plaques seen in hand and foot psoriasis—and other forms of psoriasis—can interfere with work and usual daily activities. UVA or narrowband UVB light therapy is a treatment option but requires 3 visits per week, which is not conducive to most people’s work schedules. Acitretin can be prescribed to decrease the abnormal proliferation of keratinocytes; however, adverse reactions can be expected, like this patient’s dry skin and itching. Furthermore, acitretin is a retinoid, like isotretinoin, which can cause severe birth defects, as well as hypertriglyceridemia and transaminitis. Pregnancy needs to be avoided for 3 years due to the teratogenicity and long washout period, so it should not be used in women with reproductive potential.¹

This patient was initially treated with topical calcipotriene (a vitamin D derivative) and clobetasol (high-potency topical steroid) bid but did not have adequate improvement. Screening lab tests showed elevated liver enzymes, precluding treatment with methotrexate (and acitretin, which he’d received previously). He was started on apremilast, an oral phosphodiesterase inhibitor, because his insurance denied adalimumab. Apremilast can cause diarrhea, depression, nausea, and headache. Other than some loose stools, the patient tolerated apremilast well and showed significant improvement in his psoriasis at his 3-month follow-up visit.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had hand and foot psoriasis with the classic thick scale and erythema on his palms and soles. Additionally, in the area of the sole toward the heel, he had hyperpigmented macules called mahogany spots that are another hallmark of psoriasis. Pitting and distal onycholysis were also visible on his right ring finger.

This case illustrates how the painful plaques seen in hand and foot psoriasis—and other forms of psoriasis—can interfere with work and usual daily activities. UVA or narrowband UVB light therapy is a treatment option but requires 3 visits per week, which is not conducive to most people’s work schedules. Acitretin can be prescribed to decrease the abnormal proliferation of keratinocytes; however, adverse reactions can be expected, like this patient’s dry skin and itching. Furthermore, acitretin is a retinoid, like isotretinoin, which can cause severe birth defects, as well as hypertriglyceridemia and transaminitis. Pregnancy needs to be avoided for 3 years due to the teratogenicity and long washout period, so it should not be used in women with reproductive potential.¹

This patient was initially treated with topical calcipotriene (a vitamin D derivative) and clobetasol (high-potency topical steroid) bid but did not have adequate improvement. Screening lab tests showed elevated liver enzymes, precluding treatment with methotrexate (and acitretin, which he’d received previously). He was started on apremilast, an oral phosphodiesterase inhibitor, because his insurance denied adalimumab. Apremilast can cause diarrhea, depression, nausea, and headache. Other than some loose stools, the patient tolerated apremilast well and showed significant improvement in his psoriasis at his 3-month follow-up visit.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had hand and foot psoriasis with the classic thick scale and erythema on his palms and soles. Additionally, in the area of the sole toward the heel, he had hyperpigmented macules called mahogany spots that are another hallmark of psoriasis. Pitting and distal onycholysis were also visible on his right ring finger.

This case illustrates how the painful plaques seen in hand and foot psoriasis—and other forms of psoriasis—can interfere with work and usual daily activities. UVA or narrowband UVB light therapy is a treatment option but requires 3 visits per week, which is not conducive to most people’s work schedules. Acitretin can be prescribed to decrease the abnormal proliferation of keratinocytes; however, adverse reactions can be expected, like this patient’s dry skin and itching. Furthermore, acitretin is a retinoid, like isotretinoin, which can cause severe birth defects, as well as hypertriglyceridemia and transaminitis. Pregnancy needs to be avoided for 3 years due to the teratogenicity and long washout period, so it should not be used in women with reproductive potential.¹

This patient was initially treated with topical calcipotriene (a vitamin D derivative) and clobetasol (high-potency topical steroid) bid but did not have adequate improvement. Screening lab tests showed elevated liver enzymes, precluding treatment with methotrexate (and acitretin, which he’d received previously). He was started on apremilast, an oral phosphodiesterase inhibitor, because his insurance denied adalimumab. Apremilast can cause diarrhea, depression, nausea, and headache. Other than some loose stools, the patient tolerated apremilast well and showed significant improvement in his psoriasis at his 3-month follow-up visit.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

New findings suggest the Janssen/Johnson & Johnson COVID-19 vaccine can reduce the risk of an immunized person unknowingly passing along the virus to others.

Johnson & Johnson

The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.

“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.

“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.

“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”

The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.

The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.

The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.

In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.

If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.

Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Novel research from the Concussion Assessment, Research and Education (CARE) Consortium sheds new light on how to effectively reduce the incidence of concussion and head injury exposure in college football.

The study, led by neurotrauma experts Michael McCrea, PhD, and Brian Stemper, PhD, professors of neurosurgery at the Medical College of Wisconsin in Milwaukee, reports data from hundreds of college football players across five seasons and shows concussion incidence and head injury exposure are disproportionately higher in the preseason versus the regular season.

The research also reveals that such injuries occur more often during practices than games.

“We think that with the findings from this paper, there’s a role for everybody to play in reducing injury,” Dr. McCrea said. “We hope these data help inform broad-based policy about practice and preseason training policies in collegiate football. We also think there’s a role for athletic administrators, coaches, and even athletes themselves.”

The study was published online Feb. 1 in JAMA Neurology.
 

More injuries in preseason

Concussion is one of the most common injuries in football. Beyond these harms are growing concerns that repetitive HIE may increase the risk of long-term neurologic health problems including chronic traumatic encephalopathy (CTE).

The CARE Consortium, which has been conducting research with college athletes across 26 sports and military cadets since 2014, has been interested in multiple facets of concussion and brain trauma.

“We’ve enrolled more than 50,000 athletes and service academy cadets into the consortium over the last 6 years to research all involved aspects including the clinical core, the imaging core, the blood biomarker core, and the genetic core, and we have a head impact measurement core.”

To investigate the pattern of concussion incidence across the football season in college players, the investigators used impact measurement technology across six Division I NCAA football programs participating in the CARE Consortium from 2015 to 2019.

A total of 658 players – all male, mean age 19 years – were fitted with the Head Impact Telemetry System (HITS) sensor arrays in their helmets to measure head impact frequency, location, and magnitude during play.

“This particular study had built-in algorithms that weeded out impacts that were below 10G of linear magnitude, because those have been determined not likely to be real impacts,” Dr. McCrea said.

Across the five seasons studied, 528,684 head impacts recorded met the quality standards for analysis. Players sustained a median of 415 (interquartile range [IQR], 190-727) impacts per season.

Of those, 68 players sustained a diagnosed concussion. In total, 48.5% of concussions occurred during preseason training, despite preseason representing only 20.8% of the football season. Total head injury exposure in the preseason occurred at twice the proportion of the regular season (324.9 vs. 162.4 impacts per team per day; mean difference, 162.6 impacts; 95% confidence interval, 110.9-214.3; P < .001).

“Preseason training often has a much higher intensity to it, in terms of the total hours, the actual training, and the heavy emphasis on full-contact drills like tackling and blocking,” said Dr. McCrea. “Even the volume of players that are participating is greater.”

Results also showed that in each of the five seasons, head injury exposure per athlete was highest in August (preseason) (median, 146.0 impacts; IQR, 63.0-247.8) and lowest in November (median, 80.0 impacts; IQR, 35.0-148.0). In the studied period, 72% of concussions and 66.9% of head injury exposure occurred in practice. Even within the regular season, total head injury exposure in practices was 84.2% higher than in games.

“This incredible dataset we have on head impact measurement also gives us the opportunity to compare it with our other research looking at the correlation between a single head impact and changes in brain structure and function on MRI, on blood biomarkers, giving us the ability to look at the connection between mechanism of effect of injury and recovery from injury,” said Dr. McCrea.

These findings also provide an opportunity to modify approaches to preseason training and football practices to keep players safer, said Dr. McCrea, noting that about half of the variance in head injury exposure is at the level of the individual athlete.

“With this large body of athletes we’ve instrumented, we can look at, for instance, all of the running backs and understand the athlete and what his head injury exposure looks like compared to all other running backs. If we find out that an athlete has a rate of head injury exposure that’s 300% higher than most other players that play the same position, we can take that data directly to the athlete to work on their technique and approach to the game.

“Every researcher wishes that their basic science or their clinical research findings will have some impact on the health and well-being of the population they’re studying. By modifying practices and preseason training, football teams could greatly reduce the risk of injury and exposure for their players, while still maintaining the competitive nature of game play,” he added.  

Through a combination of policy and education, similar strategies could be implemented to help prevent concussion and HIE in high school and youth football too, said Dr. McCrea.

‘Shocking’ findings

In an accompanying editorial, Christopher J. Nowinski, PhD, of the Concussion Legacy Foundation, Boston, and Robert C. Cantu, MD, department of neurosurgery, Emerson Hospital, Concord, Massachusetts, said the findings could have significant policy implications and offer a valuable expansion of prior research.

“From 2005 to 2010, studies on college football revealed that about two-thirds of head impacts occurred in practice,” they noted. “We cited this data in 2010 when we proposed to the NFL Players Association that the most effective way to reduce the risks of negative neurological outcomes was to reduce hitting in practice. They agreed, and in 2011 collectively bargained for severe contact limits in practice, with 14 full-contact practices allowed during the 17-week season. Since that rule was implemented, only 18% of NFL concussions have occurred in practice.”

“Against this backdrop, the results of the study by McCrea et al. are shocking,” they added. “It reveals that college football players still experience 72% of their concussions and 67% of their total head injury exposure in practice.”

Even more shocking, noted Dr. Nowinski and Dr. Cantu, is that these numbers are almost certainly an underestimate of the dangers of practice.

“As a former college football player and a former team physician, respectively, we find this situation inexcusable. Concussions in games are inevitable, but concussions in practice are preventable,” they wrote.  

“Laudably,” they added “the investigators call on the NCAA and football conferences to explore policy and rule changes to reduce concussion incidence and HIE and to create robust educational offerings to encourage change from coaches and college administrators.”

A version of this article first appeared on Medscape.com.

Novel research from the Concussion Assessment, Research and Education (CARE) Consortium sheds new light on how to effectively reduce the incidence of concussion and head injury exposure in college football.

The study, led by neurotrauma experts Michael McCrea, PhD, and Brian Stemper, PhD, professors of neurosurgery at the Medical College of Wisconsin in Milwaukee, reports data from hundreds of college football players across five seasons and shows concussion incidence and head injury exposure are disproportionately higher in the preseason versus the regular season.

The research also reveals that such injuries occur more often during practices than games.

“We think that with the findings from this paper, there’s a role for everybody to play in reducing injury,” Dr. McCrea said. “We hope these data help inform broad-based policy about practice and preseason training policies in collegiate football. We also think there’s a role for athletic administrators, coaches, and even athletes themselves.”

The study was published online Feb. 1 in JAMA Neurology.
 

More injuries in preseason

Concussion is one of the most common injuries in football. Beyond these harms are growing concerns that repetitive HIE may increase the risk of long-term neurologic health problems including chronic traumatic encephalopathy (CTE).

The CARE Consortium, which has been conducting research with college athletes across 26 sports and military cadets since 2014, has been interested in multiple facets of concussion and brain trauma.

“We’ve enrolled more than 50,000 athletes and service academy cadets into the consortium over the last 6 years to research all involved aspects including the clinical core, the imaging core, the blood biomarker core, and the genetic core, and we have a head impact measurement core.”

To investigate the pattern of concussion incidence across the football season in college players, the investigators used impact measurement technology across six Division I NCAA football programs participating in the CARE Consortium from 2015 to 2019.

A total of 658 players – all male, mean age 19 years – were fitted with the Head Impact Telemetry System (HITS) sensor arrays in their helmets to measure head impact frequency, location, and magnitude during play.

“This particular study had built-in algorithms that weeded out impacts that were below 10G of linear magnitude, because those have been determined not likely to be real impacts,” Dr. McCrea said.

Across the five seasons studied, 528,684 head impacts recorded met the quality standards for analysis. Players sustained a median of 415 (interquartile range [IQR], 190-727) impacts per season.

Of those, 68 players sustained a diagnosed concussion. In total, 48.5% of concussions occurred during preseason training, despite preseason representing only 20.8% of the football season. Total head injury exposure in the preseason occurred at twice the proportion of the regular season (324.9 vs. 162.4 impacts per team per day; mean difference, 162.6 impacts; 95% confidence interval, 110.9-214.3; P < .001).

“Preseason training often has a much higher intensity to it, in terms of the total hours, the actual training, and the heavy emphasis on full-contact drills like tackling and blocking,” said Dr. McCrea. “Even the volume of players that are participating is greater.”

Results also showed that in each of the five seasons, head injury exposure per athlete was highest in August (preseason) (median, 146.0 impacts; IQR, 63.0-247.8) and lowest in November (median, 80.0 impacts; IQR, 35.0-148.0). In the studied period, 72% of concussions and 66.9% of head injury exposure occurred in practice. Even within the regular season, total head injury exposure in practices was 84.2% higher than in games.

“This incredible dataset we have on head impact measurement also gives us the opportunity to compare it with our other research looking at the correlation between a single head impact and changes in brain structure and function on MRI, on blood biomarkers, giving us the ability to look at the connection between mechanism of effect of injury and recovery from injury,” said Dr. McCrea.

These findings also provide an opportunity to modify approaches to preseason training and football practices to keep players safer, said Dr. McCrea, noting that about half of the variance in head injury exposure is at the level of the individual athlete.

“With this large body of athletes we’ve instrumented, we can look at, for instance, all of the running backs and understand the athlete and what his head injury exposure looks like compared to all other running backs. If we find out that an athlete has a rate of head injury exposure that’s 300% higher than most other players that play the same position, we can take that data directly to the athlete to work on their technique and approach to the game.

“Every researcher wishes that their basic science or their clinical research findings will have some impact on the health and well-being of the population they’re studying. By modifying practices and preseason training, football teams could greatly reduce the risk of injury and exposure for their players, while still maintaining the competitive nature of game play,” he added.  

Through a combination of policy and education, similar strategies could be implemented to help prevent concussion and HIE in high school and youth football too, said Dr. McCrea.

‘Shocking’ findings

In an accompanying editorial, Christopher J. Nowinski, PhD, of the Concussion Legacy Foundation, Boston, and Robert C. Cantu, MD, department of neurosurgery, Emerson Hospital, Concord, Massachusetts, said the findings could have significant policy implications and offer a valuable expansion of prior research.

“From 2005 to 2010, studies on college football revealed that about two-thirds of head impacts occurred in practice,” they noted. “We cited this data in 2010 when we proposed to the NFL Players Association that the most effective way to reduce the risks of negative neurological outcomes was to reduce hitting in practice. They agreed, and in 2011 collectively bargained for severe contact limits in practice, with 14 full-contact practices allowed during the 17-week season. Since that rule was implemented, only 18% of NFL concussions have occurred in practice.”

“Against this backdrop, the results of the study by McCrea et al. are shocking,” they added. “It reveals that college football players still experience 72% of their concussions and 67% of their total head injury exposure in practice.”

Even more shocking, noted Dr. Nowinski and Dr. Cantu, is that these numbers are almost certainly an underestimate of the dangers of practice.

“As a former college football player and a former team physician, respectively, we find this situation inexcusable. Concussions in games are inevitable, but concussions in practice are preventable,” they wrote.  

“Laudably,” they added “the investigators call on the NCAA and football conferences to explore policy and rule changes to reduce concussion incidence and HIE and to create robust educational offerings to encourage change from coaches and college administrators.”

A version of this article first appeared on Medscape.com.

Novel research from the Concussion Assessment, Research and Education (CARE) Consortium sheds new light on how to effectively reduce the incidence of concussion and head injury exposure in college football.

The study, led by neurotrauma experts Michael McCrea, PhD, and Brian Stemper, PhD, professors of neurosurgery at the Medical College of Wisconsin in Milwaukee, reports data from hundreds of college football players across five seasons and shows concussion incidence and head injury exposure are disproportionately higher in the preseason versus the regular season.

The research also reveals that such injuries occur more often during practices than games.

“We think that with the findings from this paper, there’s a role for everybody to play in reducing injury,” Dr. McCrea said. “We hope these data help inform broad-based policy about practice and preseason training policies in collegiate football. We also think there’s a role for athletic administrators, coaches, and even athletes themselves.”

The study was published online Feb. 1 in JAMA Neurology.
 

More injuries in preseason

Concussion is one of the most common injuries in football. Beyond these harms are growing concerns that repetitive HIE may increase the risk of long-term neurologic health problems including chronic traumatic encephalopathy (CTE).

The CARE Consortium, which has been conducting research with college athletes across 26 sports and military cadets since 2014, has been interested in multiple facets of concussion and brain trauma.

“We’ve enrolled more than 50,000 athletes and service academy cadets into the consortium over the last 6 years to research all involved aspects including the clinical core, the imaging core, the blood biomarker core, and the genetic core, and we have a head impact measurement core.”

To investigate the pattern of concussion incidence across the football season in college players, the investigators used impact measurement technology across six Division I NCAA football programs participating in the CARE Consortium from 2015 to 2019.

A total of 658 players – all male, mean age 19 years – were fitted with the Head Impact Telemetry System (HITS) sensor arrays in their helmets to measure head impact frequency, location, and magnitude during play.

“This particular study had built-in algorithms that weeded out impacts that were below 10G of linear magnitude, because those have been determined not likely to be real impacts,” Dr. McCrea said.

Across the five seasons studied, 528,684 head impacts recorded met the quality standards for analysis. Players sustained a median of 415 (interquartile range [IQR], 190-727) impacts per season.

Of those, 68 players sustained a diagnosed concussion. In total, 48.5% of concussions occurred during preseason training, despite preseason representing only 20.8% of the football season. Total head injury exposure in the preseason occurred at twice the proportion of the regular season (324.9 vs. 162.4 impacts per team per day; mean difference, 162.6 impacts; 95% confidence interval, 110.9-214.3; P < .001).

“Preseason training often has a much higher intensity to it, in terms of the total hours, the actual training, and the heavy emphasis on full-contact drills like tackling and blocking,” said Dr. McCrea. “Even the volume of players that are participating is greater.”

Results also showed that in each of the five seasons, head injury exposure per athlete was highest in August (preseason) (median, 146.0 impacts; IQR, 63.0-247.8) and lowest in November (median, 80.0 impacts; IQR, 35.0-148.0). In the studied period, 72% of concussions and 66.9% of head injury exposure occurred in practice. Even within the regular season, total head injury exposure in practices was 84.2% higher than in games.

“This incredible dataset we have on head impact measurement also gives us the opportunity to compare it with our other research looking at the correlation between a single head impact and changes in brain structure and function on MRI, on blood biomarkers, giving us the ability to look at the connection between mechanism of effect of injury and recovery from injury,” said Dr. McCrea.

These findings also provide an opportunity to modify approaches to preseason training and football practices to keep players safer, said Dr. McCrea, noting that about half of the variance in head injury exposure is at the level of the individual athlete.

“With this large body of athletes we’ve instrumented, we can look at, for instance, all of the running backs and understand the athlete and what his head injury exposure looks like compared to all other running backs. If we find out that an athlete has a rate of head injury exposure that’s 300% higher than most other players that play the same position, we can take that data directly to the athlete to work on their technique and approach to the game.

“Every researcher wishes that their basic science or their clinical research findings will have some impact on the health and well-being of the population they’re studying. By modifying practices and preseason training, football teams could greatly reduce the risk of injury and exposure for their players, while still maintaining the competitive nature of game play,” he added.  

Through a combination of policy and education, similar strategies could be implemented to help prevent concussion and HIE in high school and youth football too, said Dr. McCrea.

‘Shocking’ findings

In an accompanying editorial, Christopher J. Nowinski, PhD, of the Concussion Legacy Foundation, Boston, and Robert C. Cantu, MD, department of neurosurgery, Emerson Hospital, Concord, Massachusetts, said the findings could have significant policy implications and offer a valuable expansion of prior research.

“From 2005 to 2010, studies on college football revealed that about two-thirds of head impacts occurred in practice,” they noted. “We cited this data in 2010 when we proposed to the NFL Players Association that the most effective way to reduce the risks of negative neurological outcomes was to reduce hitting in practice. They agreed, and in 2011 collectively bargained for severe contact limits in practice, with 14 full-contact practices allowed during the 17-week season. Since that rule was implemented, only 18% of NFL concussions have occurred in practice.”

“Against this backdrop, the results of the study by McCrea et al. are shocking,” they added. “It reveals that college football players still experience 72% of their concussions and 67% of their total head injury exposure in practice.”

Even more shocking, noted Dr. Nowinski and Dr. Cantu, is that these numbers are almost certainly an underestimate of the dangers of practice.

“As a former college football player and a former team physician, respectively, we find this situation inexcusable. Concussions in games are inevitable, but concussions in practice are preventable,” they wrote.  

“Laudably,” they added “the investigators call on the NCAA and football conferences to explore policy and rule changes to reduce concussion incidence and HIE and to create robust educational offerings to encourage change from coaches and college administrators.”

A version of this article first appeared on Medscape.com.

I think there are multiple factors explaining why the percentage of family physicians treating children declined again. Not the least of these is that pediatricians have a very limited scope of practice and need to market and attract patients, which they do quite a bit. There are even pediatric urgent care centers popping up all over the place now, some likely funded by venture capital just as other urgent care centers have been funded.

The loss of pediatric inpatient volume because of the effectiveness of vaccines that prevent many bacterial and viral illnesses means that fewer pediatric graduates are spending time in the hospital.

Family doctors used to retain their pediatric patients by delivering babies, seeing them in the newborn nursery, and beginning their relationship with the kids there. FPs are delivering fewer babies and the subsequent reduction in new kids in their practices has been a factor in this as well.

Finally, in multispecialty practices, pediatricians are employed there. Families immediately assume that their kids should be going to the pediatricians, not the family doctors. We need to keep talking up the fact that we take care of whole families to retain our pediatric practices.

Neil S. Calman, MD, is president and chief executive officer of the Institute for Family Health and is professor and chair of the Alfred and Gail Engelberg department of family medicine and community health at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Health System, both in New York. Dr. Calman also serves on the editorial advisory board of Family Practice News.

I think there are multiple factors explaining why the percentage of family physicians treating children declined again. Not the least of these is that pediatricians have a very limited scope of practice and need to market and attract patients, which they do quite a bit. There are even pediatric urgent care centers popping up all over the place now, some likely funded by venture capital just as other urgent care centers have been funded.

The loss of pediatric inpatient volume because of the effectiveness of vaccines that prevent many bacterial and viral illnesses means that fewer pediatric graduates are spending time in the hospital.

Family doctors used to retain their pediatric patients by delivering babies, seeing them in the newborn nursery, and beginning their relationship with the kids there. FPs are delivering fewer babies and the subsequent reduction in new kids in their practices has been a factor in this as well.

Finally, in multispecialty practices, pediatricians are employed there. Families immediately assume that their kids should be going to the pediatricians, not the family doctors. We need to keep talking up the fact that we take care of whole families to retain our pediatric practices.

Neil S. Calman, MD, is president and chief executive officer of the Institute for Family Health and is professor and chair of the Alfred and Gail Engelberg department of family medicine and community health at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Health System, both in New York. Dr. Calman also serves on the editorial advisory board of Family Practice News.

I think there are multiple factors explaining why the percentage of family physicians treating children declined again. Not the least of these is that pediatricians have a very limited scope of practice and need to market and attract patients, which they do quite a bit. There are even pediatric urgent care centers popping up all over the place now, some likely funded by venture capital just as other urgent care centers have been funded.

The loss of pediatric inpatient volume because of the effectiveness of vaccines that prevent many bacterial and viral illnesses means that fewer pediatric graduates are spending time in the hospital.

Family doctors used to retain their pediatric patients by delivering babies, seeing them in the newborn nursery, and beginning their relationship with the kids there. FPs are delivering fewer babies and the subsequent reduction in new kids in their practices has been a factor in this as well.

Finally, in multispecialty practices, pediatricians are employed there. Families immediately assume that their kids should be going to the pediatricians, not the family doctors. We need to keep talking up the fact that we take care of whole families to retain our pediatric practices.

Neil S. Calman, MD, is president and chief executive officer of the Institute for Family Health and is professor and chair of the Alfred and Gail Engelberg department of family medicine and community health at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Health System, both in New York. Dr. Calman also serves on the editorial advisory board of Family Practice News.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.

Among ob.gyns. who reported burnout in the past year, 82% say they felt burned out before the advent of the coronavirus pandemic, according the Medscape Obstetrician & Gynecologist Lifestyle, Happiness, & Burnout Report.

The past year brought unusual challenges to physicians in all specialties in different ways.

“Whether on the front lines of treating COVID-19 patients, pivoting from in-person to virtual care, or even having to shutter their practices, physicians faced an onslaught of crises, while political tensions, social unrest, and environmental concerns probably affected their lives outside of medicine,” wrote Keith L. Martin and Mary Lyn Koval, both of Medscape Business of Medicine, in the introduction to the report.

Although more physicians said their burnout began prior to the pandemic, 81% of ob.gyns. reported that they were happy outside of work prior to the pandemic. However, those reporting happiness outside of work dropped to 57% after the pandemic started.

“One does not have to do a ‘deep dive’ to understand the top reasons reported for burnout,” said Mark P. Trolice, MD, director of Fertility CARE: The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando, in an interview. “Many conversations I have with colleagues are about the frustration of learning and managing electronic health records, insurance reimbursements, and a work-life balance. In addition, more physician practices are being purchased by hospitals or private-equity networks [that are] reducing and/or eliminating the autonomy of physicians.

“While all [respondents] exhibited a dramatic decline in ‘happiness’ prepandemic, compared with our current situation, ob.gyns. were no exception,” he added.

Burnout and suicidal thoughts

Overall, 26% of ob.gyn. survey respondents reported being burned out, 6% reported being depressed, and 18% reported being both burned out and depressed. Of those who reported burnout, 52% said burnout had “a strong or severe impact on my life,” while 20% reported a moderate impact and 28% reported little or no impact.

More than half (56%) of ob.gyns. who reported either depression or burnout said they had not sought professional help, although 17% reported receiving professional care in the past.

The main reason given for not seeking professional help was that burnout and depressive symptoms were not severe enough to merit it, according to 50% of respondents who reported burnout or depression but were not seeking help. In addition, 43% said they were too busy to seek help, 36% said they could deal with their symptoms without professional help, and 24% said they did not want to risk disclosure of their symptoms.

The most common cause of burnout was an overload of bureaucratic tasks, reported by 52% of respondents, followed by “lack of respect from administrators/employers, colleagues, or staff” (43%), and insufficient compensation or reimbursement (39%).

Notably, 19% of ob.gyns. reported suicidal thoughts, and 1% said they had attempted suicide.

“The most concerning statistic from this survey was in reference to suicidal ideation,” said Dr. Trolice. “Approximately one in five ob.gyns. have contemplated suicide, compared with 4.8% of adults age 18 and older in the U.S. reporting in 2019.”

Dr. Trolice said he was not surprised that relatively few ob.gyns. sought help for mental health issues. “Physicians are very private and usually do not seek help from colleagues, presumably from hubris. While this is unfortunate, all hospitals and health care organization should implement regular assessments of physicians’ health to ensure optimal performance from a professional and personal basis.”
 

Balance and self-care

The top workplace concern, by a large margin, was for work-life balance, reported by 44% of respondents, followed by compensation (19%), combining work and parenting (18%), and relationships with staff and colleagues (8%).

Approximately one-third (36%) of the ob.gyn. respondents said they made time to focus on personal well-being, compared with 35% of physicians overall. Although only 13% reported exercising every day, a total of 69% exercised at least twice a week, similar to the 70% of physicians overall who reported exercising at least twice a week.

“Work-life balance is high on the list of concerns, but physicians are split 50/50 on whether they would accept a salary reduction to improve this aspect of their lives,” Dr. Trolice said.

“Social relationships are a proven value to mental health, yet nearly 50% of ob.gyns. who reported feeling burnout use isolationism as their coping skill, citing a lack of severity to require treatment,” he noted. Nevertheless, more than 80% of responders were married and described their relationship as “good or very good.”

Address burnout at individual and organizational levels

“Sadly, the findings are not surprising,” said Iris Krisha, MD, of Emory University, Atlanta, in an interview. “Burnout rates have been steadily increasing among physicians across all specialties.” Barriers to reducing burnout exist at the organizational and individual level, therefore strategies to reduce burnout should address individual and organizational solutions, Dr. Krishna emphasized. “At the organizational level, solutions may include developing manageable workloads, creating fair productivity targets, encouraging physician engagement in work structure, supporting flexible work schedules, and allowing for protected time for education and exercise. On the individual level, physicians can work to develop stress management strategies, engage in mindfulness and self-care.”

To reduce the burden of bureaucratic tasks, “health care organizations can work toward optimizing electronic medical records and hire staff to offload clerical work, and physicians can seek training in efficiency,” said Dr. Krishna. In addition, “health care organizations can reduce the stigma that may surround burnout or mental health issues, as well as promote a culture of wellness and resilience,” to help reduce and prevent burnout.  
 

Find positivity and purpose

Improving the workplace experience so physicians feel engaged and in control as they navigate their many responsibilities may help reduce burnout, said Dr. Trolice. On the individual level, “finding your purpose to give you more meaning at work, discovering the power of hope to embrace optimism, and building friendships at work for greater engagement with others,” can help as well.

“In the face of adversity and setbacks, people in happier workplaces tend to be better at coping with and recovering from work pressure and at reconciling conflict,” Dr. Trolice emphasized. “The practice of medicine has dramatically changed for many physicians compared with the original expectations when they applied to medical school. Nevertheless, it behooves physician to adapt to 21^st century medical care as they remind themselves of their purpose.”

The report included responses from 12,339 physicians across 29 specialties who completed a 10-minute online survey between Aug. 30 and Nov. 5, 2020. Participants were required to be practicing U.S. physicians.