User login
Staff education cuts psychotropic drug use in long-term care
The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.
The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.
There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.
“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.
Heavy drug use
Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.
To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.
Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).
Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.
The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.
Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
Short-term benefit
As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.
By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.
Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.
In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.
Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).
“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.
The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
Randomized design
In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”
“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.
Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.
Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.
Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”
Dr. Aalto and Dr. Ryg had no disclosures.
The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.
The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.
There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.
“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.
Heavy drug use
Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.
To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.
Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).
Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.
The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.
Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
Short-term benefit
As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.
By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.
Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.
In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.
Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).
“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.
The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
Randomized design
In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”
“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.
Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.
Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.
Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”
Dr. Aalto and Dr. Ryg had no disclosures.
The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.
The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.
There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.
“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.
Heavy drug use
Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.
To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.
Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).
Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.
The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.
Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
Short-term benefit
As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.
By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.
Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.
In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.
Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).
“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.
The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
Randomized design
In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”
“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.
Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.
Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.
Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”
Dr. Aalto and Dr. Ryg had no disclosures.
FROM EUGMS 2021
Low preconception complement levels linked to adverse pregnancy outcomes in antiphospholipid syndrome
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Is the end near for surgical and transbronchial biopsies? Challenges in the pediatric workforce; Cascade testing in PAH; and more ...
Interventional chest/diagnostic procedures
Endobronchial optical coherence tomography and interstitial lung diseases: Is the end near for surgical and transbronchial lung biopsies?
The early diagnosis of interstitial lung diseases (ILD) is paramount to initiating appropriate treatment and preventing irreversible pulmonary damage. Specific ILD subtypes may be diagnosed based on clinical evaluation, high resolution chest CT (HRCT) patterns, and serologic testing, but many patients require invasive procedures for histopathologic evaluation of lung tissue. Current modalities for obtaining tissue include transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB), both of which carry a risk of potential complications (Troy LK, et al. Lancet Respir Med. 2020;8:171-81; Hutchinson JP, et al. Am J Respir Crit Care Med. 2016;193[10]:1161-7).
Recently, genomic classifiers applied to transbronchial biopsies have been proposed to facilitate the diagnosis of usual interstitial pneumonia (UIP), but the limited information provided still does not obviate the need for tissue diagnosis when needed (Raghu G, et al. Lancet Respir Med. 2019;7[6]:487-96). It is in this context that endobronchial optical coherence tomography (EB-OCT) was proposed as a real-time, in vivo, optical biopsy method for ILD.
EB-OCT uses near infrared light to generate large volumes of in-vivo three-dimensional tissue imaging with microscopic resolution (Goorsenberg A, et al. Respiration. 2020;99:190-205; Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). The OCT catheter is advanced through the bronchoscope working channel and can be used during outpatient procedures under conscious sedation. Available data suggests that minimal training is necessary, both for proceduralists and interpreting pathologists, but this will need to be confirmed in larger studies and various practice settings. Early studies suggest that OCT can identify microscopic honeycombing and other abnormalities even before they are evident on HRCT scans (Goorsenberg A, et al. Respiration. 2020;99:190-205). Newer research comparing ILD diagnosis from EB-OCT cross-sectional images with that obtained from SLB specimens revealed EB-OCT can distinguish UIP from non-UIP ILD with high sensitivity and specificity (Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). Could this mean the end of SLB and TBLC for the diagnosis of ILD? While the ability to diagnose ILD subtypes with high reliability and low risk of complications is certainly promising, studies remain admittedly small and the technique itself is only available to highly select individuals and specialized ILD centers. Let’s not pack up the cryoprobe just yet.
Audra J. Schwalk, MD, MBA: Steering Committee Member
Fabien Maldonado, MD, FCCP: Steering Committee Member
Pediatric chest medicine
Challenges in the pediatric pulmonary workforce
The future of the pediatric workforce has been the source of extensive discussion within the pediatric community and resulted in a considerable body of medical literature (Vinci RJ. Pediatrics. 2021;147[6]:e2020013292). In pediatric pulmonology, there is growing concern that current trends will lead to a workforce shortage resulting in patients having difficulty accessing subspecialty care (Harris C, et al. Pediatric Pulmonol. 2019;54[4]:444-50). The etiology of this shortage is multifactorial. Duration of fellowship training and subsequent financial implications are reported potential barriers to pursuing a fellowship (Nelson BA, et al. Pediatric Pulmonol. 2020;1-7). Discrepancies between pediatric and adult compensation may be another barrier. Insightful recruitment strategies based on the results of a recent study included maximizing resident interaction with pulmonary faculty, early identification and support of interested trainees, and consideration of flexible training models (Nelson BA, et al. ATS Sch. 2020;1:372-83). Lifestyle has also been a factor that contributes to a trainee’s decision to go into pediatric pulmonology (Freed GL, et al. Pediatrics. 2009;123(suppl 1):S31‐S37).
As our field addresses the critical need to recruit more trainees in light of the unfilled fellowship positions and the increasing average age of members of the field, we should not underestimate the prevalence of systemic racism and bias in medicine (Chiel L, et al. ATS Sch. 2020;1[4]:337-39) nor gender discrimination. Instead, we should seize the opportunity to understand and knock down barriers that trainees who are underrepresented in medicine face in pursuing pediatric subspecialty careers and build upon the excellent recent body of literature in this field to help recruit, support , and grow a robust, diverse workforce to provide the best pediatric care to all.
Anne C. Coates, MD – Steering Committee Member
Pulmonary vascular disease
Cascade testing in PAH: Is there a role?
Pediatric guidelines for pulmonary arterial hypertension (PAH) recommends genetic screening as a part of the evaluation for the newly diagnosed, with expansion to first-degree relatives as indicated. Currently, this is not mandated, and implementation is variable. In adults, genetic screening is not routinely offered, and family screening is rare. This reflects a lack of definitive guidelines (Abman SH, et al. Circulation. 2015:24;132[21]:2037-99). However, it is intuitive that if carriers are not identified by screening, they will come to attention after pulmonary vascular disease burden causes symptoms and affects outcomes.
Cascade testing is a screening methodology that is used in heritable cancers (George RM, et al. Genet Couns. 2015;24[3]:388-99). In cascade testing, identification of an index case prompts screening of at-risk family members. If these relatives are positive for mutations, the cycle is repeated (cascaded) to their immediate relatives, allowing for targeted screening. This approach is especially effective in genetic mutations that are inherited in an autosomal dominant fashion, such as in BMPR2 gene mutation. Cascade testing is an effective way to capture relatives who would otherwise be overlooked.
Unfortunately, in the United States, the cost of genetic testing is a significant obstacle to universal implementation. A new diagnosis of heritable pulmonary arterial hypertension (HPAH) is often followed by a multigene panel with costs exceeding $1000 and may prompt subsequent targeted testing resulting in additional expense (Chung WK, et al. Can J Cardiol. 2015;31[4]:544-47). Furthermore, a positive mutation detected on screening is not definitively associated with disease due to variable penetrance (Morrell NW, et al. Eur Respir J. 2019;53[1]:1801899]. As such, mass screening strategies are not recommended. The recent DELPHI-2 study [Montani D, et al. Eur Respir J. 2021;58[1]:2004229) have demonstrated that genetic screening is impactful in families with HPAH. A genetic screening algorithm should be considered, and cascade testing could be a cost-effective targeted approach.
Sandeep Sahay, MD, MSc, FCCP: Steering Committee Member
Jean M. Elwing, MD, FCCP: Chair
Pulmonary physiology, function, and rehabilitation network
Physiological benefits of awake proning: Its role and relevance in the COVID-19 pandemic
The advent of the COVID-19 pandemic has put a significant strain on the health care systems and critical care services across several countries, including the United States. Amidst this, several concerted efforts to reduce the need for mechanical ventilation has resulted in the emergence of awake proning as a strategy to improve oxygenation, which has been instituted in critical care units, in-patient settings, as well as in EDs. Although the evidence on this strategy has been vastly limited to case series and observational studies, several societies have incorporated awake proning as an initial management strategy in hypoxemic respiratory failure within their clinical guidelines (Chalmers JD, et al. Eur Respir J. 2021;57:2100048; Koeckerling D, et al. Thorax. 2020;75:833-4) and consensus statements (Nasa P, et al. Crit Care. 2021;25:106).
Physiological benefits of awake proning include improvement in ventilation-perfusion matching secondary to relative increase in ventilation in dorsal nondependent areas in the setting of higher density of perfusion within these units, thus reducing shunt and, hence, improving oxygenation. Other physiological mechanisms include homogenization of transpulmonary pressures, reduction of ventilator-induced lung injury (VILI) or patient self-inflicted lung injury (P-SILI), and possibly lung injury from pendelluft (Telias I, et al. JAMA. 2020;323[22]:2265-67).
A recent meta-trial involving randomized controlled trials done across six countries compared prone positioning with standard care in patients with hypoxemic respiratory failure (defined as SpO2/ FiO2 < 315 and on high flow oxygen therapy) showed a reduced incidence of treatment failure and need for intubation without any signal of harm; although no mortality benefit was reported (Ehrmann S, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600(21)00356-8). The number needed to treat to prevent one intubation was 14. While promising and reinforcing the safety of this relatively easy maneuver, several questions remain—which patients would benefit the most? Can it be applied within general wards safely? Does institution of awake proning delay intubation rates with consequent worse outcomes? Several ongoing (NCT 04402879) and completed studies (NCT 04383613 and NCT 04350723) may shed light on these important questions (Weatherald J, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600[21]00368-4).
Sujith Cherian, MD, FCCP: Steering Committee Member
Interventional chest/diagnostic procedures
Endobronchial optical coherence tomography and interstitial lung diseases: Is the end near for surgical and transbronchial lung biopsies?
The early diagnosis of interstitial lung diseases (ILD) is paramount to initiating appropriate treatment and preventing irreversible pulmonary damage. Specific ILD subtypes may be diagnosed based on clinical evaluation, high resolution chest CT (HRCT) patterns, and serologic testing, but many patients require invasive procedures for histopathologic evaluation of lung tissue. Current modalities for obtaining tissue include transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB), both of which carry a risk of potential complications (Troy LK, et al. Lancet Respir Med. 2020;8:171-81; Hutchinson JP, et al. Am J Respir Crit Care Med. 2016;193[10]:1161-7).
Recently, genomic classifiers applied to transbronchial biopsies have been proposed to facilitate the diagnosis of usual interstitial pneumonia (UIP), but the limited information provided still does not obviate the need for tissue diagnosis when needed (Raghu G, et al. Lancet Respir Med. 2019;7[6]:487-96). It is in this context that endobronchial optical coherence tomography (EB-OCT) was proposed as a real-time, in vivo, optical biopsy method for ILD.
EB-OCT uses near infrared light to generate large volumes of in-vivo three-dimensional tissue imaging with microscopic resolution (Goorsenberg A, et al. Respiration. 2020;99:190-205; Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). The OCT catheter is advanced through the bronchoscope working channel and can be used during outpatient procedures under conscious sedation. Available data suggests that minimal training is necessary, both for proceduralists and interpreting pathologists, but this will need to be confirmed in larger studies and various practice settings. Early studies suggest that OCT can identify microscopic honeycombing and other abnormalities even before they are evident on HRCT scans (Goorsenberg A, et al. Respiration. 2020;99:190-205). Newer research comparing ILD diagnosis from EB-OCT cross-sectional images with that obtained from SLB specimens revealed EB-OCT can distinguish UIP from non-UIP ILD with high sensitivity and specificity (Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). Could this mean the end of SLB and TBLC for the diagnosis of ILD? While the ability to diagnose ILD subtypes with high reliability and low risk of complications is certainly promising, studies remain admittedly small and the technique itself is only available to highly select individuals and specialized ILD centers. Let’s not pack up the cryoprobe just yet.
Audra J. Schwalk, MD, MBA: Steering Committee Member
Fabien Maldonado, MD, FCCP: Steering Committee Member
Pediatric chest medicine
Challenges in the pediatric pulmonary workforce
The future of the pediatric workforce has been the source of extensive discussion within the pediatric community and resulted in a considerable body of medical literature (Vinci RJ. Pediatrics. 2021;147[6]:e2020013292). In pediatric pulmonology, there is growing concern that current trends will lead to a workforce shortage resulting in patients having difficulty accessing subspecialty care (Harris C, et al. Pediatric Pulmonol. 2019;54[4]:444-50). The etiology of this shortage is multifactorial. Duration of fellowship training and subsequent financial implications are reported potential barriers to pursuing a fellowship (Nelson BA, et al. Pediatric Pulmonol. 2020;1-7). Discrepancies between pediatric and adult compensation may be another barrier. Insightful recruitment strategies based on the results of a recent study included maximizing resident interaction with pulmonary faculty, early identification and support of interested trainees, and consideration of flexible training models (Nelson BA, et al. ATS Sch. 2020;1:372-83). Lifestyle has also been a factor that contributes to a trainee’s decision to go into pediatric pulmonology (Freed GL, et al. Pediatrics. 2009;123(suppl 1):S31‐S37).
As our field addresses the critical need to recruit more trainees in light of the unfilled fellowship positions and the increasing average age of members of the field, we should not underestimate the prevalence of systemic racism and bias in medicine (Chiel L, et al. ATS Sch. 2020;1[4]:337-39) nor gender discrimination. Instead, we should seize the opportunity to understand and knock down barriers that trainees who are underrepresented in medicine face in pursuing pediatric subspecialty careers and build upon the excellent recent body of literature in this field to help recruit, support , and grow a robust, diverse workforce to provide the best pediatric care to all.
Anne C. Coates, MD – Steering Committee Member
Pulmonary vascular disease
Cascade testing in PAH: Is there a role?
Pediatric guidelines for pulmonary arterial hypertension (PAH) recommends genetic screening as a part of the evaluation for the newly diagnosed, with expansion to first-degree relatives as indicated. Currently, this is not mandated, and implementation is variable. In adults, genetic screening is not routinely offered, and family screening is rare. This reflects a lack of definitive guidelines (Abman SH, et al. Circulation. 2015:24;132[21]:2037-99). However, it is intuitive that if carriers are not identified by screening, they will come to attention after pulmonary vascular disease burden causes symptoms and affects outcomes.
Cascade testing is a screening methodology that is used in heritable cancers (George RM, et al. Genet Couns. 2015;24[3]:388-99). In cascade testing, identification of an index case prompts screening of at-risk family members. If these relatives are positive for mutations, the cycle is repeated (cascaded) to their immediate relatives, allowing for targeted screening. This approach is especially effective in genetic mutations that are inherited in an autosomal dominant fashion, such as in BMPR2 gene mutation. Cascade testing is an effective way to capture relatives who would otherwise be overlooked.
Unfortunately, in the United States, the cost of genetic testing is a significant obstacle to universal implementation. A new diagnosis of heritable pulmonary arterial hypertension (HPAH) is often followed by a multigene panel with costs exceeding $1000 and may prompt subsequent targeted testing resulting in additional expense (Chung WK, et al. Can J Cardiol. 2015;31[4]:544-47). Furthermore, a positive mutation detected on screening is not definitively associated with disease due to variable penetrance (Morrell NW, et al. Eur Respir J. 2019;53[1]:1801899]. As such, mass screening strategies are not recommended. The recent DELPHI-2 study [Montani D, et al. Eur Respir J. 2021;58[1]:2004229) have demonstrated that genetic screening is impactful in families with HPAH. A genetic screening algorithm should be considered, and cascade testing could be a cost-effective targeted approach.
Sandeep Sahay, MD, MSc, FCCP: Steering Committee Member
Jean M. Elwing, MD, FCCP: Chair
Pulmonary physiology, function, and rehabilitation network
Physiological benefits of awake proning: Its role and relevance in the COVID-19 pandemic
The advent of the COVID-19 pandemic has put a significant strain on the health care systems and critical care services across several countries, including the United States. Amidst this, several concerted efforts to reduce the need for mechanical ventilation has resulted in the emergence of awake proning as a strategy to improve oxygenation, which has been instituted in critical care units, in-patient settings, as well as in EDs. Although the evidence on this strategy has been vastly limited to case series and observational studies, several societies have incorporated awake proning as an initial management strategy in hypoxemic respiratory failure within their clinical guidelines (Chalmers JD, et al. Eur Respir J. 2021;57:2100048; Koeckerling D, et al. Thorax. 2020;75:833-4) and consensus statements (Nasa P, et al. Crit Care. 2021;25:106).
Physiological benefits of awake proning include improvement in ventilation-perfusion matching secondary to relative increase in ventilation in dorsal nondependent areas in the setting of higher density of perfusion within these units, thus reducing shunt and, hence, improving oxygenation. Other physiological mechanisms include homogenization of transpulmonary pressures, reduction of ventilator-induced lung injury (VILI) or patient self-inflicted lung injury (P-SILI), and possibly lung injury from pendelluft (Telias I, et al. JAMA. 2020;323[22]:2265-67).
A recent meta-trial involving randomized controlled trials done across six countries compared prone positioning with standard care in patients with hypoxemic respiratory failure (defined as SpO2/ FiO2 < 315 and on high flow oxygen therapy) showed a reduced incidence of treatment failure and need for intubation without any signal of harm; although no mortality benefit was reported (Ehrmann S, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600(21)00356-8). The number needed to treat to prevent one intubation was 14. While promising and reinforcing the safety of this relatively easy maneuver, several questions remain—which patients would benefit the most? Can it be applied within general wards safely? Does institution of awake proning delay intubation rates with consequent worse outcomes? Several ongoing (NCT 04402879) and completed studies (NCT 04383613 and NCT 04350723) may shed light on these important questions (Weatherald J, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600[21]00368-4).
Sujith Cherian, MD, FCCP: Steering Committee Member
Interventional chest/diagnostic procedures
Endobronchial optical coherence tomography and interstitial lung diseases: Is the end near for surgical and transbronchial lung biopsies?
The early diagnosis of interstitial lung diseases (ILD) is paramount to initiating appropriate treatment and preventing irreversible pulmonary damage. Specific ILD subtypes may be diagnosed based on clinical evaluation, high resolution chest CT (HRCT) patterns, and serologic testing, but many patients require invasive procedures for histopathologic evaluation of lung tissue. Current modalities for obtaining tissue include transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB), both of which carry a risk of potential complications (Troy LK, et al. Lancet Respir Med. 2020;8:171-81; Hutchinson JP, et al. Am J Respir Crit Care Med. 2016;193[10]:1161-7).
Recently, genomic classifiers applied to transbronchial biopsies have been proposed to facilitate the diagnosis of usual interstitial pneumonia (UIP), but the limited information provided still does not obviate the need for tissue diagnosis when needed (Raghu G, et al. Lancet Respir Med. 2019;7[6]:487-96). It is in this context that endobronchial optical coherence tomography (EB-OCT) was proposed as a real-time, in vivo, optical biopsy method for ILD.
EB-OCT uses near infrared light to generate large volumes of in-vivo three-dimensional tissue imaging with microscopic resolution (Goorsenberg A, et al. Respiration. 2020;99:190-205; Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). The OCT catheter is advanced through the bronchoscope working channel and can be used during outpatient procedures under conscious sedation. Available data suggests that minimal training is necessary, both for proceduralists and interpreting pathologists, but this will need to be confirmed in larger studies and various practice settings. Early studies suggest that OCT can identify microscopic honeycombing and other abnormalities even before they are evident on HRCT scans (Goorsenberg A, et al. Respiration. 2020;99:190-205). Newer research comparing ILD diagnosis from EB-OCT cross-sectional images with that obtained from SLB specimens revealed EB-OCT can distinguish UIP from non-UIP ILD with high sensitivity and specificity (Nandy S, et al. Am J Respir Crit Care Med. 2021;article in press). Could this mean the end of SLB and TBLC for the diagnosis of ILD? While the ability to diagnose ILD subtypes with high reliability and low risk of complications is certainly promising, studies remain admittedly small and the technique itself is only available to highly select individuals and specialized ILD centers. Let’s not pack up the cryoprobe just yet.
Audra J. Schwalk, MD, MBA: Steering Committee Member
Fabien Maldonado, MD, FCCP: Steering Committee Member
Pediatric chest medicine
Challenges in the pediatric pulmonary workforce
The future of the pediatric workforce has been the source of extensive discussion within the pediatric community and resulted in a considerable body of medical literature (Vinci RJ. Pediatrics. 2021;147[6]:e2020013292). In pediatric pulmonology, there is growing concern that current trends will lead to a workforce shortage resulting in patients having difficulty accessing subspecialty care (Harris C, et al. Pediatric Pulmonol. 2019;54[4]:444-50). The etiology of this shortage is multifactorial. Duration of fellowship training and subsequent financial implications are reported potential barriers to pursuing a fellowship (Nelson BA, et al. Pediatric Pulmonol. 2020;1-7). Discrepancies between pediatric and adult compensation may be another barrier. Insightful recruitment strategies based on the results of a recent study included maximizing resident interaction with pulmonary faculty, early identification and support of interested trainees, and consideration of flexible training models (Nelson BA, et al. ATS Sch. 2020;1:372-83). Lifestyle has also been a factor that contributes to a trainee’s decision to go into pediatric pulmonology (Freed GL, et al. Pediatrics. 2009;123(suppl 1):S31‐S37).
As our field addresses the critical need to recruit more trainees in light of the unfilled fellowship positions and the increasing average age of members of the field, we should not underestimate the prevalence of systemic racism and bias in medicine (Chiel L, et al. ATS Sch. 2020;1[4]:337-39) nor gender discrimination. Instead, we should seize the opportunity to understand and knock down barriers that trainees who are underrepresented in medicine face in pursuing pediatric subspecialty careers and build upon the excellent recent body of literature in this field to help recruit, support , and grow a robust, diverse workforce to provide the best pediatric care to all.
Anne C. Coates, MD – Steering Committee Member
Pulmonary vascular disease
Cascade testing in PAH: Is there a role?
Pediatric guidelines for pulmonary arterial hypertension (PAH) recommends genetic screening as a part of the evaluation for the newly diagnosed, with expansion to first-degree relatives as indicated. Currently, this is not mandated, and implementation is variable. In adults, genetic screening is not routinely offered, and family screening is rare. This reflects a lack of definitive guidelines (Abman SH, et al. Circulation. 2015:24;132[21]:2037-99). However, it is intuitive that if carriers are not identified by screening, they will come to attention after pulmonary vascular disease burden causes symptoms and affects outcomes.
Cascade testing is a screening methodology that is used in heritable cancers (George RM, et al. Genet Couns. 2015;24[3]:388-99). In cascade testing, identification of an index case prompts screening of at-risk family members. If these relatives are positive for mutations, the cycle is repeated (cascaded) to their immediate relatives, allowing for targeted screening. This approach is especially effective in genetic mutations that are inherited in an autosomal dominant fashion, such as in BMPR2 gene mutation. Cascade testing is an effective way to capture relatives who would otherwise be overlooked.
Unfortunately, in the United States, the cost of genetic testing is a significant obstacle to universal implementation. A new diagnosis of heritable pulmonary arterial hypertension (HPAH) is often followed by a multigene panel with costs exceeding $1000 and may prompt subsequent targeted testing resulting in additional expense (Chung WK, et al. Can J Cardiol. 2015;31[4]:544-47). Furthermore, a positive mutation detected on screening is not definitively associated with disease due to variable penetrance (Morrell NW, et al. Eur Respir J. 2019;53[1]:1801899]. As such, mass screening strategies are not recommended. The recent DELPHI-2 study [Montani D, et al. Eur Respir J. 2021;58[1]:2004229) have demonstrated that genetic screening is impactful in families with HPAH. A genetic screening algorithm should be considered, and cascade testing could be a cost-effective targeted approach.
Sandeep Sahay, MD, MSc, FCCP: Steering Committee Member
Jean M. Elwing, MD, FCCP: Chair
Pulmonary physiology, function, and rehabilitation network
Physiological benefits of awake proning: Its role and relevance in the COVID-19 pandemic
The advent of the COVID-19 pandemic has put a significant strain on the health care systems and critical care services across several countries, including the United States. Amidst this, several concerted efforts to reduce the need for mechanical ventilation has resulted in the emergence of awake proning as a strategy to improve oxygenation, which has been instituted in critical care units, in-patient settings, as well as in EDs. Although the evidence on this strategy has been vastly limited to case series and observational studies, several societies have incorporated awake proning as an initial management strategy in hypoxemic respiratory failure within their clinical guidelines (Chalmers JD, et al. Eur Respir J. 2021;57:2100048; Koeckerling D, et al. Thorax. 2020;75:833-4) and consensus statements (Nasa P, et al. Crit Care. 2021;25:106).
Physiological benefits of awake proning include improvement in ventilation-perfusion matching secondary to relative increase in ventilation in dorsal nondependent areas in the setting of higher density of perfusion within these units, thus reducing shunt and, hence, improving oxygenation. Other physiological mechanisms include homogenization of transpulmonary pressures, reduction of ventilator-induced lung injury (VILI) or patient self-inflicted lung injury (P-SILI), and possibly lung injury from pendelluft (Telias I, et al. JAMA. 2020;323[22]:2265-67).
A recent meta-trial involving randomized controlled trials done across six countries compared prone positioning with standard care in patients with hypoxemic respiratory failure (defined as SpO2/ FiO2 < 315 and on high flow oxygen therapy) showed a reduced incidence of treatment failure and need for intubation without any signal of harm; although no mortality benefit was reported (Ehrmann S, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600(21)00356-8). The number needed to treat to prevent one intubation was 14. While promising and reinforcing the safety of this relatively easy maneuver, several questions remain—which patients would benefit the most? Can it be applied within general wards safely? Does institution of awake proning delay intubation rates with consequent worse outcomes? Several ongoing (NCT 04402879) and completed studies (NCT 04383613 and NCT 04350723) may shed light on these important questions (Weatherald J, et al. Lancet Respir Med. 2021 Aug 20;S2213-2600[21]00368-4).
Sujith Cherian, MD, FCCP: Steering Committee Member
Thoughts on becoming CHEST President
I am honored to have the privilege of serving as the 84th President of the American College of Chest Physicians. When I attended my first CHEST meeting, I sat in the opening plenary session with thousands of other members, never imagining that I would have the opportunity to lead the organization just two decades later. And while I don’t recall many sessions from that meeting, I vividly remember the way it made an emotional impact. I never felt like one of a drove of nameless learners; both faculty and staff made it a collegial experience, much like attending pulmonary grand rounds at my own institution. Speakers would stay after their presentations to answer questions from even the most junior members. Leadership made themselves available over coffee or in the hallways between sessions. And that experience was the first of a great many memorable interactions I have had with CHEST.
CHEST has meant a great deal to me personally; it served as my first professional home away from home. I had the opportunity to grow in a number of different areas through my service to CHEST, in ways that I would not have been able to do easily at my own institution. I’ve worked with incredible staff and volunteers in my service on a number of our committees, including the Council of NetWorks, the Training and Transitions Committee, the Education Committee, and the Program Committee, to name a few. While I’ve had a chance to learn what role each of these component parts of the College serves during my tenure on those committees, it wasn’t until far more recently that I better understood the role of the President. Before I get into what I’d like to achieve during my year as President, I’d like to briefly review what that role entails.
Contrary to popular belief, the President does not set the organizational goals for CHEST; those are set by the Board of Regents. While I will have the privilege of running the Board meetings, it is the seventeen incredibly talented folks who serve as voting members of the Board that set the College’s direction. Once the organizational goals are set, it is our committees that take charge of designing and implementing plans to work toward those goals. Concomitantly, Dr. Robert Musacchio (CHEST chief executive officer and executive vice president) meets with his own executive leadership team to design a structure that lets the CHEST staff work, both on their own and in tandem with our members, to achieve these goals. One of the President’s main roles, as I see it, is to serve as a liaison. When the Board makes decisions that affect the membership, it will be my job to communicate changes and why they are being made. When our members have challenges that the College might be able to help solve, it is my role to work with the Board and the CEO to see what we can do about them. And when there is need to interface with other organizations, the President (or their designee) can speak on behalf of the College in those interactions.
In the context of those duties, what are the things that I would like to accomplish during my tenure as CHEST president? First, I want to spend more time with our committees and you, our members. CHEST is a member-focused organization; I believe that this is the main thing that sets our professional society apart from its sister societies. I have always found CHEST to be very collegial and welcoming. But I am aware that some of our members haven’t always found it accessible. And I get that; our structure is complex. That’s the reason I provided a description of my role, and the reason that I intend to spend time making CHEST more accessible to all of you. We’ve already developed dedicated social media channels for a number of our NetWorks in order to make you all more aware of their activities. In the coming year, I’ll provide regular updates to membership about ongoing CHEST activities. I’ll work to provide more member awareness of what role each of our committees plays in forwarding the College’s goals. And I’ll provide you with more information about the type of qualifications that each committee seeks in its nominees, in an effort to encourage you to run for a leadership position that best suits your interests and skill set.
While improving our members’ understanding of the inner workings at CHEST will help each of you better see how the College can meet your needs, my hope is that this increase in organizational accessibility will motivate each of you to engage more actively with us. This is my second goal as President. For some of you, that engagement may take the form of joining our Twitter chats; for others, it could mean attending one of our live learning courses in Chicago for the first time. But I hope that some of you will consider submitting session proposals to our annual meeting for the first time, or running for an available leadership position within the College when nominations open in the Spring.
As our organization grows (now almost twenty thousand members strong!), I want to provide a second home for all our members, spanning the range from medical students to full professors, from lifelong academic physicians to those just starting out in community practices, from busy clinicians to physician scientists, and including all members of the healthcare team. Although the makeup of our volunteer leadership is becoming more representative of the full breadth of our membership, we are not fully there yet. Until we get to that intended target, I would like to ask each of you to reach out to me with any thoughts about how CHEST can better meet your professional needs. Creating greater access to leadership to let each of your opinions be heard is my third goal as President of CHEST. I’ll provide more details about how I’m hoping to achieve this in the coming months.
The world has been a crazy place over the last eighteen months, filled with challenges that we could never have foreseen even a year prior. Our members have been on the front lines of the pandemic; in addition to the professional stresses related to caring for innumerable critically ill patients, many of us have suffered personal losses. Although none of us knows what 2022 holds, I look forward to a brighter future, knowing that regardless of what the coming year brings, we will face it together.
I am honored to have the privilege of serving as the 84th President of the American College of Chest Physicians. When I attended my first CHEST meeting, I sat in the opening plenary session with thousands of other members, never imagining that I would have the opportunity to lead the organization just two decades later. And while I don’t recall many sessions from that meeting, I vividly remember the way it made an emotional impact. I never felt like one of a drove of nameless learners; both faculty and staff made it a collegial experience, much like attending pulmonary grand rounds at my own institution. Speakers would stay after their presentations to answer questions from even the most junior members. Leadership made themselves available over coffee or in the hallways between sessions. And that experience was the first of a great many memorable interactions I have had with CHEST.
CHEST has meant a great deal to me personally; it served as my first professional home away from home. I had the opportunity to grow in a number of different areas through my service to CHEST, in ways that I would not have been able to do easily at my own institution. I’ve worked with incredible staff and volunteers in my service on a number of our committees, including the Council of NetWorks, the Training and Transitions Committee, the Education Committee, and the Program Committee, to name a few. While I’ve had a chance to learn what role each of these component parts of the College serves during my tenure on those committees, it wasn’t until far more recently that I better understood the role of the President. Before I get into what I’d like to achieve during my year as President, I’d like to briefly review what that role entails.
Contrary to popular belief, the President does not set the organizational goals for CHEST; those are set by the Board of Regents. While I will have the privilege of running the Board meetings, it is the seventeen incredibly talented folks who serve as voting members of the Board that set the College’s direction. Once the organizational goals are set, it is our committees that take charge of designing and implementing plans to work toward those goals. Concomitantly, Dr. Robert Musacchio (CHEST chief executive officer and executive vice president) meets with his own executive leadership team to design a structure that lets the CHEST staff work, both on their own and in tandem with our members, to achieve these goals. One of the President’s main roles, as I see it, is to serve as a liaison. When the Board makes decisions that affect the membership, it will be my job to communicate changes and why they are being made. When our members have challenges that the College might be able to help solve, it is my role to work with the Board and the CEO to see what we can do about them. And when there is need to interface with other organizations, the President (or their designee) can speak on behalf of the College in those interactions.
In the context of those duties, what are the things that I would like to accomplish during my tenure as CHEST president? First, I want to spend more time with our committees and you, our members. CHEST is a member-focused organization; I believe that this is the main thing that sets our professional society apart from its sister societies. I have always found CHEST to be very collegial and welcoming. But I am aware that some of our members haven’t always found it accessible. And I get that; our structure is complex. That’s the reason I provided a description of my role, and the reason that I intend to spend time making CHEST more accessible to all of you. We’ve already developed dedicated social media channels for a number of our NetWorks in order to make you all more aware of their activities. In the coming year, I’ll provide regular updates to membership about ongoing CHEST activities. I’ll work to provide more member awareness of what role each of our committees plays in forwarding the College’s goals. And I’ll provide you with more information about the type of qualifications that each committee seeks in its nominees, in an effort to encourage you to run for a leadership position that best suits your interests and skill set.
While improving our members’ understanding of the inner workings at CHEST will help each of you better see how the College can meet your needs, my hope is that this increase in organizational accessibility will motivate each of you to engage more actively with us. This is my second goal as President. For some of you, that engagement may take the form of joining our Twitter chats; for others, it could mean attending one of our live learning courses in Chicago for the first time. But I hope that some of you will consider submitting session proposals to our annual meeting for the first time, or running for an available leadership position within the College when nominations open in the Spring.
As our organization grows (now almost twenty thousand members strong!), I want to provide a second home for all our members, spanning the range from medical students to full professors, from lifelong academic physicians to those just starting out in community practices, from busy clinicians to physician scientists, and including all members of the healthcare team. Although the makeup of our volunteer leadership is becoming more representative of the full breadth of our membership, we are not fully there yet. Until we get to that intended target, I would like to ask each of you to reach out to me with any thoughts about how CHEST can better meet your professional needs. Creating greater access to leadership to let each of your opinions be heard is my third goal as President of CHEST. I’ll provide more details about how I’m hoping to achieve this in the coming months.
The world has been a crazy place over the last eighteen months, filled with challenges that we could never have foreseen even a year prior. Our members have been on the front lines of the pandemic; in addition to the professional stresses related to caring for innumerable critically ill patients, many of us have suffered personal losses. Although none of us knows what 2022 holds, I look forward to a brighter future, knowing that regardless of what the coming year brings, we will face it together.
I am honored to have the privilege of serving as the 84th President of the American College of Chest Physicians. When I attended my first CHEST meeting, I sat in the opening plenary session with thousands of other members, never imagining that I would have the opportunity to lead the organization just two decades later. And while I don’t recall many sessions from that meeting, I vividly remember the way it made an emotional impact. I never felt like one of a drove of nameless learners; both faculty and staff made it a collegial experience, much like attending pulmonary grand rounds at my own institution. Speakers would stay after their presentations to answer questions from even the most junior members. Leadership made themselves available over coffee or in the hallways between sessions. And that experience was the first of a great many memorable interactions I have had with CHEST.
CHEST has meant a great deal to me personally; it served as my first professional home away from home. I had the opportunity to grow in a number of different areas through my service to CHEST, in ways that I would not have been able to do easily at my own institution. I’ve worked with incredible staff and volunteers in my service on a number of our committees, including the Council of NetWorks, the Training and Transitions Committee, the Education Committee, and the Program Committee, to name a few. While I’ve had a chance to learn what role each of these component parts of the College serves during my tenure on those committees, it wasn’t until far more recently that I better understood the role of the President. Before I get into what I’d like to achieve during my year as President, I’d like to briefly review what that role entails.
Contrary to popular belief, the President does not set the organizational goals for CHEST; those are set by the Board of Regents. While I will have the privilege of running the Board meetings, it is the seventeen incredibly talented folks who serve as voting members of the Board that set the College’s direction. Once the organizational goals are set, it is our committees that take charge of designing and implementing plans to work toward those goals. Concomitantly, Dr. Robert Musacchio (CHEST chief executive officer and executive vice president) meets with his own executive leadership team to design a structure that lets the CHEST staff work, both on their own and in tandem with our members, to achieve these goals. One of the President’s main roles, as I see it, is to serve as a liaison. When the Board makes decisions that affect the membership, it will be my job to communicate changes and why they are being made. When our members have challenges that the College might be able to help solve, it is my role to work with the Board and the CEO to see what we can do about them. And when there is need to interface with other organizations, the President (or their designee) can speak on behalf of the College in those interactions.
In the context of those duties, what are the things that I would like to accomplish during my tenure as CHEST president? First, I want to spend more time with our committees and you, our members. CHEST is a member-focused organization; I believe that this is the main thing that sets our professional society apart from its sister societies. I have always found CHEST to be very collegial and welcoming. But I am aware that some of our members haven’t always found it accessible. And I get that; our structure is complex. That’s the reason I provided a description of my role, and the reason that I intend to spend time making CHEST more accessible to all of you. We’ve already developed dedicated social media channels for a number of our NetWorks in order to make you all more aware of their activities. In the coming year, I’ll provide regular updates to membership about ongoing CHEST activities. I’ll work to provide more member awareness of what role each of our committees plays in forwarding the College’s goals. And I’ll provide you with more information about the type of qualifications that each committee seeks in its nominees, in an effort to encourage you to run for a leadership position that best suits your interests and skill set.
While improving our members’ understanding of the inner workings at CHEST will help each of you better see how the College can meet your needs, my hope is that this increase in organizational accessibility will motivate each of you to engage more actively with us. This is my second goal as President. For some of you, that engagement may take the form of joining our Twitter chats; for others, it could mean attending one of our live learning courses in Chicago for the first time. But I hope that some of you will consider submitting session proposals to our annual meeting for the first time, or running for an available leadership position within the College when nominations open in the Spring.
As our organization grows (now almost twenty thousand members strong!), I want to provide a second home for all our members, spanning the range from medical students to full professors, from lifelong academic physicians to those just starting out in community practices, from busy clinicians to physician scientists, and including all members of the healthcare team. Although the makeup of our volunteer leadership is becoming more representative of the full breadth of our membership, we are not fully there yet. Until we get to that intended target, I would like to ask each of you to reach out to me with any thoughts about how CHEST can better meet your professional needs. Creating greater access to leadership to let each of your opinions be heard is my third goal as President of CHEST. I’ll provide more details about how I’m hoping to achieve this in the coming months.
The world has been a crazy place over the last eighteen months, filled with challenges that we could never have foreseen even a year prior. Our members have been on the front lines of the pandemic; in addition to the professional stresses related to caring for innumerable critically ill patients, many of us have suffered personal losses. Although none of us knows what 2022 holds, I look forward to a brighter future, knowing that regardless of what the coming year brings, we will face it together.
TTM2: Is there anything therapeutic about therapeutic hypothermia?
Animal and human models of the effects of therapeutic hypothermia, now called targeted temperature management (TTM), began to surface in the late 1980s. The first randomized clinical trial employing TTM as a neuroprotective strategy following cardiac arrest did not appear until the early 2000s. When compared with normothermia, the HACA trial (Holzer M, et al. N Engl J Med. 2002;346[8]:549-56) demonstrated a 14% reduction in mortality and improved neurologic outcomes following out of hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) or ventricular tachycardia (VT) when maintaining body temperature between 32˚C and 34˚C post-arrest. Following the results of this trial, TTM in comatose patients following cardiac arrest was recommended by international guidelines and became the standard of care. It was not until the publication of the TTM1 trial (Nielsen N, et al. N Engl J Med. 2013;369[23]:2197-206) about a decade later, that serious questions regarding the efficacy of TTM were raised. The TTM1 trial showed no difference in mortality or neurologic outcomes when comparing TTM at 33˚C vs 36˚C for OHCA. The results of this trial heralded widespread practice change, with many abandoning deep cooling, and often active cooling measures, in favor of fever avoidance. The HYPERION trial (Lascarrou J, et al. N Engl J Med. 2019;381:2327-37) came next, comparing TTM at 33˚C to normothermia (<37.5˚C) for cardiac arrest with non-hockable rhythm. This study did not identify any improvement in mortality with utilization of TTM but suggested it may be associated with more favorable neurologic outcomes, albeit in a small number of patients.
The TTM2 trial (Dankiewicz J, et al. N Engl J Med. 2021;384:2283-94) is the most recent trial to address the question of TTM post-cardiac arrest. The TTM2 trial was an international, randomized controlled superiority trial of TTM at 33˚C vs normothermia (≤37.8˚C) for patients with coma following OHCA with any initial rhythm. It was conducted by the same group as the TTM1 trial and, to date, represents the largest (N= 1,850) and most robust trial conducted in this area. The trial spanned 61 institutions across 14 countries and had nearly complete follow-up at 6 months. Once again, there was no significant difference in all-cause mortality at 6 months in the TTM group when compared with the normothermia group. Equally important, there were no differences observed in secondary outcomes, including functional neurologic status and health-related quality of life at 6 months. With the results of the TTM1 and TTM2 trials failing to show any neurologic or mortality benefit to TTM, we are left wondering, is there anything therapeutic about “therapeutic hypothermia”?
Both the 2020 American Heart Association (AHA) and 2021 European Resuscitation Council (ERC) guidelines predate this trial; they recommend cooling any OHCA or in-hospital cardiac arrest (IHCA) patient who remains unresponsive after return of spontaneous circulation (ROSC) regardless of initial rhythm. They further suggest maintaining a target temperature between 32˚C and 36˚C for at least 24 hours, followed by avoidance of fever (>37.7˚C) for at least 72 hours after ROSC in patients who remain comatose. While it will be interesting to see what future iterations of the guidelines recommend, the results from the TTM1 and TTM2 trials support a shift in clinical practice away from TTM and toward more active fever avoidance. Additionally, careful review of adverse events in the TTM2 trial suggests that induced hypothermia is not without risk of harm. When compared with the normothermia group in the TTM2 trial, the hypothermia group experienced higher rates of arrhythmias with hemodynamic instability (16% vs 24%), increased exposure to sedation, increased use of neuromuscular blockade, and increased duration of mechanical ventilation.
While the results of the TTM2 trial move the needle away from therapeutic hypothermia for OHCA patients, there is some nuance that warrants further discussion. First, the initial HACA trial, upon which the standard of TTM was based, included only patients with an initial shockable rhythm (VT/VF). Inherently, the etiology of these arrests is likely to be cardiac and more reversible in nature. Most subsequent landmark trials on TTM, including the TTM2 trial, have included OHCA patients with both shockable and nonshockable initial rhythms. Still, the majority of patients in the TTM2 trial had an initial shockable rhythm on presentation (72% hypothermia vs 75% normothermia). This may limit broad generalizability of study findings as an increasing number of OHCA patients are presenting with nonshockable initial rhythms. Next, it is well known that bystander CPR improves outcomes following OHCA. Impressively, over 75% of patients in both groups in the TTM2 trial received bystander CPR compared with an average of 46% of arrest patients in the US according to AHA data. Finally, like most of its predecessors, the TTM2 trial only included OHCA patients meaning no real conclusions can be drawn regarding application of TTM to IHCA patients. Of the major trials to date, only the HYPERION trial included IHCA patients – representing about 25% of the study population. Thus, the utility of TTM in the setting of IHCA remains largely unknown.
Taken in summation, recent trials, including TTM2, suggest that fever-avoidance post-cardiac arrest is likely the best option for improving mortality and neurologic outcomes while mitigating risk to the patient. We must remain vigilant in our enforcement of normothermia though as worse neurologic outcomes have been observed with hyperthermia in the early post-arrest period (Zeiner A, et al. Arch Intern Med. 2001;161[16]:2007-12). A key takeaway from recent trials is that maintaining normothermia without active temperature control measures is likely to be difficult to achieve. A criticism of the HYPERION trial was that a “substantial proportion” of patients in the normothermia group had temperatures above 38˚C. Similarly, 10% to15% of patients in the TTM2 trial had body temperatures above 37.7˚C, 40 to 72 hours after randomization and, ultimately, 46% of patients in the normothermia group required cooling with a temperature management device. Thus, we can conclude that maintenance of strict normothermia will likely continue to require active control with a temperature management device.
Despite an increasing number of well conducted studies in this area, there are several questions that remain unanswered. The first is whether cooling patients even earlier post-arrest is felt to increase the likelihood of survival with improved neurologic outcomes. Like HACA and HYPERION, the rate of cooling in the TTM2 trial was relatively quick with a time to randomization after onset of cardiac arrest of about 2 hours in both groups and a median time from intervention until reaching target temperature of 3 hours. While some retrospective data suggest ultra-early cooling may be beneficial, neither induction of therapeutic hypothermia during OHCA using a rapid infusion of cold saline (Bernard SA, et al. Circulation. 2016;134[11]:797-805) nor transnasal evaporative cooling in the pre-hospital setting (Nordeberg P, et al. JAMA. 2019;321(17):1677-85) has shown improvement in survival with good neurologic outcomes. Next, if we are going to continue TTM, the TTM2 trial does not provide guidance on optimal duration of cooling. Although the current guidelines are to cool for at least 24 hours after ROSC, it is unclear for how long strict temperature control should be continued. The currently enrolling ICECAP study aims to further elucidate the optimal duration of TTM for OHCA patients with both shockable and non-shockable initial rhythms.
Post-cardiac arrest management continues to be a significant area of interest in clinical research and for good reason. Although steady improvement has occurred with regards to survival and neurologic function for IHCA, of the approximately 350,000 nontraumatic OHCA that occur in a year in the United States, only about 10.2% of those patients will survive their initial hospitalization, and only about 8.2% of those who survive will have good functional status (American Heart Association. Circulation. 2020;142(suppl 2):S366-S468). There remains much room for continued study and improvement.
Dr. Capp is a Pulmonary and Critical Care Fellow; and Dr. Pendleton is Assistant Professor of Medicine; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine; University of Minnesota, Minneapolis, Minnesota.
Animal and human models of the effects of therapeutic hypothermia, now called targeted temperature management (TTM), began to surface in the late 1980s. The first randomized clinical trial employing TTM as a neuroprotective strategy following cardiac arrest did not appear until the early 2000s. When compared with normothermia, the HACA trial (Holzer M, et al. N Engl J Med. 2002;346[8]:549-56) demonstrated a 14% reduction in mortality and improved neurologic outcomes following out of hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) or ventricular tachycardia (VT) when maintaining body temperature between 32˚C and 34˚C post-arrest. Following the results of this trial, TTM in comatose patients following cardiac arrest was recommended by international guidelines and became the standard of care. It was not until the publication of the TTM1 trial (Nielsen N, et al. N Engl J Med. 2013;369[23]:2197-206) about a decade later, that serious questions regarding the efficacy of TTM were raised. The TTM1 trial showed no difference in mortality or neurologic outcomes when comparing TTM at 33˚C vs 36˚C for OHCA. The results of this trial heralded widespread practice change, with many abandoning deep cooling, and often active cooling measures, in favor of fever avoidance. The HYPERION trial (Lascarrou J, et al. N Engl J Med. 2019;381:2327-37) came next, comparing TTM at 33˚C to normothermia (<37.5˚C) for cardiac arrest with non-hockable rhythm. This study did not identify any improvement in mortality with utilization of TTM but suggested it may be associated with more favorable neurologic outcomes, albeit in a small number of patients.
The TTM2 trial (Dankiewicz J, et al. N Engl J Med. 2021;384:2283-94) is the most recent trial to address the question of TTM post-cardiac arrest. The TTM2 trial was an international, randomized controlled superiority trial of TTM at 33˚C vs normothermia (≤37.8˚C) for patients with coma following OHCA with any initial rhythm. It was conducted by the same group as the TTM1 trial and, to date, represents the largest (N= 1,850) and most robust trial conducted in this area. The trial spanned 61 institutions across 14 countries and had nearly complete follow-up at 6 months. Once again, there was no significant difference in all-cause mortality at 6 months in the TTM group when compared with the normothermia group. Equally important, there were no differences observed in secondary outcomes, including functional neurologic status and health-related quality of life at 6 months. With the results of the TTM1 and TTM2 trials failing to show any neurologic or mortality benefit to TTM, we are left wondering, is there anything therapeutic about “therapeutic hypothermia”?
Both the 2020 American Heart Association (AHA) and 2021 European Resuscitation Council (ERC) guidelines predate this trial; they recommend cooling any OHCA or in-hospital cardiac arrest (IHCA) patient who remains unresponsive after return of spontaneous circulation (ROSC) regardless of initial rhythm. They further suggest maintaining a target temperature between 32˚C and 36˚C for at least 24 hours, followed by avoidance of fever (>37.7˚C) for at least 72 hours after ROSC in patients who remain comatose. While it will be interesting to see what future iterations of the guidelines recommend, the results from the TTM1 and TTM2 trials support a shift in clinical practice away from TTM and toward more active fever avoidance. Additionally, careful review of adverse events in the TTM2 trial suggests that induced hypothermia is not without risk of harm. When compared with the normothermia group in the TTM2 trial, the hypothermia group experienced higher rates of arrhythmias with hemodynamic instability (16% vs 24%), increased exposure to sedation, increased use of neuromuscular blockade, and increased duration of mechanical ventilation.
While the results of the TTM2 trial move the needle away from therapeutic hypothermia for OHCA patients, there is some nuance that warrants further discussion. First, the initial HACA trial, upon which the standard of TTM was based, included only patients with an initial shockable rhythm (VT/VF). Inherently, the etiology of these arrests is likely to be cardiac and more reversible in nature. Most subsequent landmark trials on TTM, including the TTM2 trial, have included OHCA patients with both shockable and nonshockable initial rhythms. Still, the majority of patients in the TTM2 trial had an initial shockable rhythm on presentation (72% hypothermia vs 75% normothermia). This may limit broad generalizability of study findings as an increasing number of OHCA patients are presenting with nonshockable initial rhythms. Next, it is well known that bystander CPR improves outcomes following OHCA. Impressively, over 75% of patients in both groups in the TTM2 trial received bystander CPR compared with an average of 46% of arrest patients in the US according to AHA data. Finally, like most of its predecessors, the TTM2 trial only included OHCA patients meaning no real conclusions can be drawn regarding application of TTM to IHCA patients. Of the major trials to date, only the HYPERION trial included IHCA patients – representing about 25% of the study population. Thus, the utility of TTM in the setting of IHCA remains largely unknown.
Taken in summation, recent trials, including TTM2, suggest that fever-avoidance post-cardiac arrest is likely the best option for improving mortality and neurologic outcomes while mitigating risk to the patient. We must remain vigilant in our enforcement of normothermia though as worse neurologic outcomes have been observed with hyperthermia in the early post-arrest period (Zeiner A, et al. Arch Intern Med. 2001;161[16]:2007-12). A key takeaway from recent trials is that maintaining normothermia without active temperature control measures is likely to be difficult to achieve. A criticism of the HYPERION trial was that a “substantial proportion” of patients in the normothermia group had temperatures above 38˚C. Similarly, 10% to15% of patients in the TTM2 trial had body temperatures above 37.7˚C, 40 to 72 hours after randomization and, ultimately, 46% of patients in the normothermia group required cooling with a temperature management device. Thus, we can conclude that maintenance of strict normothermia will likely continue to require active control with a temperature management device.
Despite an increasing number of well conducted studies in this area, there are several questions that remain unanswered. The first is whether cooling patients even earlier post-arrest is felt to increase the likelihood of survival with improved neurologic outcomes. Like HACA and HYPERION, the rate of cooling in the TTM2 trial was relatively quick with a time to randomization after onset of cardiac arrest of about 2 hours in both groups and a median time from intervention until reaching target temperature of 3 hours. While some retrospective data suggest ultra-early cooling may be beneficial, neither induction of therapeutic hypothermia during OHCA using a rapid infusion of cold saline (Bernard SA, et al. Circulation. 2016;134[11]:797-805) nor transnasal evaporative cooling in the pre-hospital setting (Nordeberg P, et al. JAMA. 2019;321(17):1677-85) has shown improvement in survival with good neurologic outcomes. Next, if we are going to continue TTM, the TTM2 trial does not provide guidance on optimal duration of cooling. Although the current guidelines are to cool for at least 24 hours after ROSC, it is unclear for how long strict temperature control should be continued. The currently enrolling ICECAP study aims to further elucidate the optimal duration of TTM for OHCA patients with both shockable and non-shockable initial rhythms.
Post-cardiac arrest management continues to be a significant area of interest in clinical research and for good reason. Although steady improvement has occurred with regards to survival and neurologic function for IHCA, of the approximately 350,000 nontraumatic OHCA that occur in a year in the United States, only about 10.2% of those patients will survive their initial hospitalization, and only about 8.2% of those who survive will have good functional status (American Heart Association. Circulation. 2020;142(suppl 2):S366-S468). There remains much room for continued study and improvement.
Dr. Capp is a Pulmonary and Critical Care Fellow; and Dr. Pendleton is Assistant Professor of Medicine; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine; University of Minnesota, Minneapolis, Minnesota.
Animal and human models of the effects of therapeutic hypothermia, now called targeted temperature management (TTM), began to surface in the late 1980s. The first randomized clinical trial employing TTM as a neuroprotective strategy following cardiac arrest did not appear until the early 2000s. When compared with normothermia, the HACA trial (Holzer M, et al. N Engl J Med. 2002;346[8]:549-56) demonstrated a 14% reduction in mortality and improved neurologic outcomes following out of hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) or ventricular tachycardia (VT) when maintaining body temperature between 32˚C and 34˚C post-arrest. Following the results of this trial, TTM in comatose patients following cardiac arrest was recommended by international guidelines and became the standard of care. It was not until the publication of the TTM1 trial (Nielsen N, et al. N Engl J Med. 2013;369[23]:2197-206) about a decade later, that serious questions regarding the efficacy of TTM were raised. The TTM1 trial showed no difference in mortality or neurologic outcomes when comparing TTM at 33˚C vs 36˚C for OHCA. The results of this trial heralded widespread practice change, with many abandoning deep cooling, and often active cooling measures, in favor of fever avoidance. The HYPERION trial (Lascarrou J, et al. N Engl J Med. 2019;381:2327-37) came next, comparing TTM at 33˚C to normothermia (<37.5˚C) for cardiac arrest with non-hockable rhythm. This study did not identify any improvement in mortality with utilization of TTM but suggested it may be associated with more favorable neurologic outcomes, albeit in a small number of patients.
The TTM2 trial (Dankiewicz J, et al. N Engl J Med. 2021;384:2283-94) is the most recent trial to address the question of TTM post-cardiac arrest. The TTM2 trial was an international, randomized controlled superiority trial of TTM at 33˚C vs normothermia (≤37.8˚C) for patients with coma following OHCA with any initial rhythm. It was conducted by the same group as the TTM1 trial and, to date, represents the largest (N= 1,850) and most robust trial conducted in this area. The trial spanned 61 institutions across 14 countries and had nearly complete follow-up at 6 months. Once again, there was no significant difference in all-cause mortality at 6 months in the TTM group when compared with the normothermia group. Equally important, there were no differences observed in secondary outcomes, including functional neurologic status and health-related quality of life at 6 months. With the results of the TTM1 and TTM2 trials failing to show any neurologic or mortality benefit to TTM, we are left wondering, is there anything therapeutic about “therapeutic hypothermia”?
Both the 2020 American Heart Association (AHA) and 2021 European Resuscitation Council (ERC) guidelines predate this trial; they recommend cooling any OHCA or in-hospital cardiac arrest (IHCA) patient who remains unresponsive after return of spontaneous circulation (ROSC) regardless of initial rhythm. They further suggest maintaining a target temperature between 32˚C and 36˚C for at least 24 hours, followed by avoidance of fever (>37.7˚C) for at least 72 hours after ROSC in patients who remain comatose. While it will be interesting to see what future iterations of the guidelines recommend, the results from the TTM1 and TTM2 trials support a shift in clinical practice away from TTM and toward more active fever avoidance. Additionally, careful review of adverse events in the TTM2 trial suggests that induced hypothermia is not without risk of harm. When compared with the normothermia group in the TTM2 trial, the hypothermia group experienced higher rates of arrhythmias with hemodynamic instability (16% vs 24%), increased exposure to sedation, increased use of neuromuscular blockade, and increased duration of mechanical ventilation.
While the results of the TTM2 trial move the needle away from therapeutic hypothermia for OHCA patients, there is some nuance that warrants further discussion. First, the initial HACA trial, upon which the standard of TTM was based, included only patients with an initial shockable rhythm (VT/VF). Inherently, the etiology of these arrests is likely to be cardiac and more reversible in nature. Most subsequent landmark trials on TTM, including the TTM2 trial, have included OHCA patients with both shockable and nonshockable initial rhythms. Still, the majority of patients in the TTM2 trial had an initial shockable rhythm on presentation (72% hypothermia vs 75% normothermia). This may limit broad generalizability of study findings as an increasing number of OHCA patients are presenting with nonshockable initial rhythms. Next, it is well known that bystander CPR improves outcomes following OHCA. Impressively, over 75% of patients in both groups in the TTM2 trial received bystander CPR compared with an average of 46% of arrest patients in the US according to AHA data. Finally, like most of its predecessors, the TTM2 trial only included OHCA patients meaning no real conclusions can be drawn regarding application of TTM to IHCA patients. Of the major trials to date, only the HYPERION trial included IHCA patients – representing about 25% of the study population. Thus, the utility of TTM in the setting of IHCA remains largely unknown.
Taken in summation, recent trials, including TTM2, suggest that fever-avoidance post-cardiac arrest is likely the best option for improving mortality and neurologic outcomes while mitigating risk to the patient. We must remain vigilant in our enforcement of normothermia though as worse neurologic outcomes have been observed with hyperthermia in the early post-arrest period (Zeiner A, et al. Arch Intern Med. 2001;161[16]:2007-12). A key takeaway from recent trials is that maintaining normothermia without active temperature control measures is likely to be difficult to achieve. A criticism of the HYPERION trial was that a “substantial proportion” of patients in the normothermia group had temperatures above 38˚C. Similarly, 10% to15% of patients in the TTM2 trial had body temperatures above 37.7˚C, 40 to 72 hours after randomization and, ultimately, 46% of patients in the normothermia group required cooling with a temperature management device. Thus, we can conclude that maintenance of strict normothermia will likely continue to require active control with a temperature management device.
Despite an increasing number of well conducted studies in this area, there are several questions that remain unanswered. The first is whether cooling patients even earlier post-arrest is felt to increase the likelihood of survival with improved neurologic outcomes. Like HACA and HYPERION, the rate of cooling in the TTM2 trial was relatively quick with a time to randomization after onset of cardiac arrest of about 2 hours in both groups and a median time from intervention until reaching target temperature of 3 hours. While some retrospective data suggest ultra-early cooling may be beneficial, neither induction of therapeutic hypothermia during OHCA using a rapid infusion of cold saline (Bernard SA, et al. Circulation. 2016;134[11]:797-805) nor transnasal evaporative cooling in the pre-hospital setting (Nordeberg P, et al. JAMA. 2019;321(17):1677-85) has shown improvement in survival with good neurologic outcomes. Next, if we are going to continue TTM, the TTM2 trial does not provide guidance on optimal duration of cooling. Although the current guidelines are to cool for at least 24 hours after ROSC, it is unclear for how long strict temperature control should be continued. The currently enrolling ICECAP study aims to further elucidate the optimal duration of TTM for OHCA patients with both shockable and non-shockable initial rhythms.
Post-cardiac arrest management continues to be a significant area of interest in clinical research and for good reason. Although steady improvement has occurred with regards to survival and neurologic function for IHCA, of the approximately 350,000 nontraumatic OHCA that occur in a year in the United States, only about 10.2% of those patients will survive their initial hospitalization, and only about 8.2% of those who survive will have good functional status (American Heart Association. Circulation. 2020;142(suppl 2):S366-S468). There remains much room for continued study and improvement.
Dr. Capp is a Pulmonary and Critical Care Fellow; and Dr. Pendleton is Assistant Professor of Medicine; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine; University of Minnesota, Minneapolis, Minnesota.
Lung transplantation for patients with severe COVID-19
As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.
For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.
There is currently little guidance regarding criteria for patient selection and consideration for LT among patients with COVID-19 ARDS. Given that the SARS-CoV-2 virus is a novel pathogen that leads to an illness that is unique from other forms of viral pneumonia, specific considerations regarding LT should be made among these patients. In the current article, we discuss some of the pertinent issues related to the consideration of LT among patients with COVID-19 ARDS.
The timing for considering LT is one of the most important aspects. First, patients with COVID-19 ARDS must not be actively infected at the time of transplantation consideration. It has been suggested that LT should only be considered in patients with two separate negative polymerase chain reaction (PCR) test results for SARS-CoV-2 from bronchoalveolar lavage fluid 24 hours apart and at least 4 weeks after the onset of COVID-19 symptoms (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30). Among patients with persistently positive SARS-CoV-2 PCR 4 to 6 weeks after symptom onset, a negative viral culture from a bronchoalveolar lavage (BAL) can be used to confirm viral inactivity (Lang C, et al. Lancet Respir Med. 2020;8[10]:1057-60).
Despite the sparse data in this domain, there seems to be a consensus in the literature that LT could be considered once 4 to 6 weeks have elapsed since the onset of the respiratory failure (Cypel M, et al. Lancet Respir Med. 2020;8[10]:944-6). This timeline is felt to be long enough to alleviate the concerns regarding ongoing inflammatory processes that may be reversible while not so long to risk the development of non-pulmonary complications or severe debility that may become significant barriers to transplant candidacy. An exception may be made in patients with medically unmanageable complications such as recalcitrant bronchopleural fistulae in the background of fibrotic changes or right ventricular failure from severe pulmonary hypertension. Regardless, this timeline is borrowed from the approach to irreversible ARDS from other forms of viral pneumonia. It is not clear if it is appropriate to extrapolate past experience to COVID-19, which is a disease unlike any other seen during the LT era: a profound inflammatory phase mediated by a cytokine storm as the etiologic basis for the organ dysfunction, activation of coagulation pathways in pulmonary circulation leading to immunothrombosis contributing to the refractory hypoxemia, favorable effects of anticoagulants, diverse pulmonary physiologic phenotypes of ARDS, an increased risk of pleural complications, and utilization of novel anti-inflammatory therapies with consequent risks ofsecondary infections are all unique to COVID-19. A recent study found that patients requiring ECMO for COVID-19 ARDS took longer to recover lung function but had similar survival rates to patients on ECMO with other virus-induced ARDS (Raff LA, et al. Am J Surg. 2021;S0002-9610[21]00233-6. doi: 10.1016/j.amjsurg.2021.04.004. Online ahead of print).These data support pursuing a more conservative timeline for consideration of LT.
Determining the reversibility of pulmonary impairment in COVID-19 ARDS is another challenge. The nature of the pulmonary opacities should be assessed on CT scan imaging as close as possible to the time of LT consideration. Differentiating the extent of irreversible parenchymal scarring vs salvageability during acute illness can be challenging. The presence of extensive architectural distortion with or without bullous changes, while being the best indicator of irreversibility, may not be sensitive enough. The standard of care in such situations remains serial assessments, often weekly, by a dedicated multidisciplinary group. We have found it useful to augment the imaging data with pulmonary physiologic assessments, including the extent of ventilator and ECMO support as well as dynamic and static compliance trends. Improvement in physiologic data often precedes radiologic improvement. Nonetheless, an important area of future research is to identify objective markers for determining reversibility, which could include novel biomarkers in serum or bronchoalveolar lavage fluid.
When a determination is made regarding the irreversibility of pulmonary impairment, the LT evaluation should begin promptly. Pre-transplant deconditioning and debility is associated with worse post-transplant outcomes. In this regard, patients managed using an ambulatory ECMO strategy may have superior rehabilitation potential. Furthermore, an attempt should be made during the evaluation to wean sedation in order to facilitate discussions regarding the rigors of LT with the patient alongside present family members. An additional consideration, given the use of immunomodulatory medications for COVID-19 and prolonged intubation, is the dramatically increased risk of multi-drug resistant infections in this population; these must be aggressively managed for patients to remain eligible for LT.
The degree of pulmonary impairment and frequent colonization of the airways will likely dictate bilateral LT as the preferred strategy, although surgical feasibility may, at times, be the overriding determinant. Regardless of the type of transplant, certain unique aspects should be anticipated. The inflammatory responses during COVID-19 that often spill outside the confines of the pulmonary parenchyma, along with potentially frequent thoracic interventions prior to transplant, create significant technical challenges during the operation. Native pneumonectomy can take longer than usual leading to prolonged ischemic time, increased need for intra-operative blood products, and raised risk for primary graft dysfunction. All of these factors have a significant impact on early and late outcomes. Finally, the long-term immunologic consequences of severe infection from a novel virus remain unknown, and it is unclear if COVID-19 ARDS patients bridged to transplant will enjoy comparable survival. It is pertinent to acknowledge that the high-risk nature of such transplants is substantially accentuated due to several unique characteristics of the illness related to COVID-19.
The emergence of the COVID-19 pandemic has led to an increase in the number of urgent inpatient lung transplant consultations for refractory ARDS. While the basic principles of LT candidate selection should continue to guide us, the unique characteristics of this illness merit using a customized approach. There are few validated predictors to guide decision-making, and longitudinal assessments by a dedicated multidisciplinary group remain the best strategy. Finally, in the absence of systemic studies and lack of longitudinal outcomes data, there is an emergent need to establish consensus guidelines regarding the approach to LT consideration in these patients.
Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.
As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.
For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.
There is currently little guidance regarding criteria for patient selection and consideration for LT among patients with COVID-19 ARDS. Given that the SARS-CoV-2 virus is a novel pathogen that leads to an illness that is unique from other forms of viral pneumonia, specific considerations regarding LT should be made among these patients. In the current article, we discuss some of the pertinent issues related to the consideration of LT among patients with COVID-19 ARDS.
The timing for considering LT is one of the most important aspects. First, patients with COVID-19 ARDS must not be actively infected at the time of transplantation consideration. It has been suggested that LT should only be considered in patients with two separate negative polymerase chain reaction (PCR) test results for SARS-CoV-2 from bronchoalveolar lavage fluid 24 hours apart and at least 4 weeks after the onset of COVID-19 symptoms (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30). Among patients with persistently positive SARS-CoV-2 PCR 4 to 6 weeks after symptom onset, a negative viral culture from a bronchoalveolar lavage (BAL) can be used to confirm viral inactivity (Lang C, et al. Lancet Respir Med. 2020;8[10]:1057-60).
Despite the sparse data in this domain, there seems to be a consensus in the literature that LT could be considered once 4 to 6 weeks have elapsed since the onset of the respiratory failure (Cypel M, et al. Lancet Respir Med. 2020;8[10]:944-6). This timeline is felt to be long enough to alleviate the concerns regarding ongoing inflammatory processes that may be reversible while not so long to risk the development of non-pulmonary complications or severe debility that may become significant barriers to transplant candidacy. An exception may be made in patients with medically unmanageable complications such as recalcitrant bronchopleural fistulae in the background of fibrotic changes or right ventricular failure from severe pulmonary hypertension. Regardless, this timeline is borrowed from the approach to irreversible ARDS from other forms of viral pneumonia. It is not clear if it is appropriate to extrapolate past experience to COVID-19, which is a disease unlike any other seen during the LT era: a profound inflammatory phase mediated by a cytokine storm as the etiologic basis for the organ dysfunction, activation of coagulation pathways in pulmonary circulation leading to immunothrombosis contributing to the refractory hypoxemia, favorable effects of anticoagulants, diverse pulmonary physiologic phenotypes of ARDS, an increased risk of pleural complications, and utilization of novel anti-inflammatory therapies with consequent risks ofsecondary infections are all unique to COVID-19. A recent study found that patients requiring ECMO for COVID-19 ARDS took longer to recover lung function but had similar survival rates to patients on ECMO with other virus-induced ARDS (Raff LA, et al. Am J Surg. 2021;S0002-9610[21]00233-6. doi: 10.1016/j.amjsurg.2021.04.004. Online ahead of print).These data support pursuing a more conservative timeline for consideration of LT.
Determining the reversibility of pulmonary impairment in COVID-19 ARDS is another challenge. The nature of the pulmonary opacities should be assessed on CT scan imaging as close as possible to the time of LT consideration. Differentiating the extent of irreversible parenchymal scarring vs salvageability during acute illness can be challenging. The presence of extensive architectural distortion with or without bullous changes, while being the best indicator of irreversibility, may not be sensitive enough. The standard of care in such situations remains serial assessments, often weekly, by a dedicated multidisciplinary group. We have found it useful to augment the imaging data with pulmonary physiologic assessments, including the extent of ventilator and ECMO support as well as dynamic and static compliance trends. Improvement in physiologic data often precedes radiologic improvement. Nonetheless, an important area of future research is to identify objective markers for determining reversibility, which could include novel biomarkers in serum or bronchoalveolar lavage fluid.
When a determination is made regarding the irreversibility of pulmonary impairment, the LT evaluation should begin promptly. Pre-transplant deconditioning and debility is associated with worse post-transplant outcomes. In this regard, patients managed using an ambulatory ECMO strategy may have superior rehabilitation potential. Furthermore, an attempt should be made during the evaluation to wean sedation in order to facilitate discussions regarding the rigors of LT with the patient alongside present family members. An additional consideration, given the use of immunomodulatory medications for COVID-19 and prolonged intubation, is the dramatically increased risk of multi-drug resistant infections in this population; these must be aggressively managed for patients to remain eligible for LT.
The degree of pulmonary impairment and frequent colonization of the airways will likely dictate bilateral LT as the preferred strategy, although surgical feasibility may, at times, be the overriding determinant. Regardless of the type of transplant, certain unique aspects should be anticipated. The inflammatory responses during COVID-19 that often spill outside the confines of the pulmonary parenchyma, along with potentially frequent thoracic interventions prior to transplant, create significant technical challenges during the operation. Native pneumonectomy can take longer than usual leading to prolonged ischemic time, increased need for intra-operative blood products, and raised risk for primary graft dysfunction. All of these factors have a significant impact on early and late outcomes. Finally, the long-term immunologic consequences of severe infection from a novel virus remain unknown, and it is unclear if COVID-19 ARDS patients bridged to transplant will enjoy comparable survival. It is pertinent to acknowledge that the high-risk nature of such transplants is substantially accentuated due to several unique characteristics of the illness related to COVID-19.
The emergence of the COVID-19 pandemic has led to an increase in the number of urgent inpatient lung transplant consultations for refractory ARDS. While the basic principles of LT candidate selection should continue to guide us, the unique characteristics of this illness merit using a customized approach. There are few validated predictors to guide decision-making, and longitudinal assessments by a dedicated multidisciplinary group remain the best strategy. Finally, in the absence of systemic studies and lack of longitudinal outcomes data, there is an emergent need to establish consensus guidelines regarding the approach to LT consideration in these patients.
Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.
As of September 2021, over 222 million people worldwide (WHO, 2021) and 40 million Americans (CDC, 2021) have been infected with the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The total number of infections in the United States began climbing again this summer with the persistence of vaccine reluctance among a significant proportion of the population and the emergence of the much more infectious B.1.617.2 (Delta) variant. While the clinical illness caused by the SARS-CoV-2 virus, referred to as the Coronavirus disease 2019 (COVID-19), is mostly mild, approximately 10% of cases develop acute respiratory distress syndrome (ARDS) (Remuzzi A, et al. Lancet. 2020;395[10231]:1225-8). A small but substantial proportion of patients with COVID-19 ARDS fails to respond to the various supportive measures and requires extracorporeal membrane oxygenation (ECMO) support. The overarching goal of the different support strategies, including ECMO, is to provide time for the lungs to recover from ARDS. ECMO has the theoretical advantage over other strategies in facilitating recovery by allowing the injured lungs to ‘rest’ as the oxygenation and ventilation needs are met in an extracorporeal fashion. Regardless, a small number of patients with COVID-19 ARDS will not recover enough pulmonary function to allow them to be weaned from the various respiratory support strategies.
For patients with irreversible lung injury, lung transplantation (LT) is a potential consideration. Earlier in the pandemic, older patients with significant comorbid illnesses were more vulnerable to severe COVID-19, often precluding consideration for transplantation. However, the emergence of the Delta variant may have altered this dynamic via a substantial increase in the incidence of COVID-19 ARDS among younger and healthier patients. A handful of patients with COVID-19 ARDS have already had successful transplantation. However, the overall number is still small (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30; and Hawkins R, et al. Transplantation. 2021;6:1381-7), and there is a lack of long-term outcomes data among these patients.
There is currently little guidance regarding criteria for patient selection and consideration for LT among patients with COVID-19 ARDS. Given that the SARS-CoV-2 virus is a novel pathogen that leads to an illness that is unique from other forms of viral pneumonia, specific considerations regarding LT should be made among these patients. In the current article, we discuss some of the pertinent issues related to the consideration of LT among patients with COVID-19 ARDS.
The timing for considering LT is one of the most important aspects. First, patients with COVID-19 ARDS must not be actively infected at the time of transplantation consideration. It has been suggested that LT should only be considered in patients with two separate negative polymerase chain reaction (PCR) test results for SARS-CoV-2 from bronchoalveolar lavage fluid 24 hours apart and at least 4 weeks after the onset of COVID-19 symptoms (Bharat A, et al. Sci Translat Med. 2020 Dec 16;12[574]:eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30). Among patients with persistently positive SARS-CoV-2 PCR 4 to 6 weeks after symptom onset, a negative viral culture from a bronchoalveolar lavage (BAL) can be used to confirm viral inactivity (Lang C, et al. Lancet Respir Med. 2020;8[10]:1057-60).
Despite the sparse data in this domain, there seems to be a consensus in the literature that LT could be considered once 4 to 6 weeks have elapsed since the onset of the respiratory failure (Cypel M, et al. Lancet Respir Med. 2020;8[10]:944-6). This timeline is felt to be long enough to alleviate the concerns regarding ongoing inflammatory processes that may be reversible while not so long to risk the development of non-pulmonary complications or severe debility that may become significant barriers to transplant candidacy. An exception may be made in patients with medically unmanageable complications such as recalcitrant bronchopleural fistulae in the background of fibrotic changes or right ventricular failure from severe pulmonary hypertension. Regardless, this timeline is borrowed from the approach to irreversible ARDS from other forms of viral pneumonia. It is not clear if it is appropriate to extrapolate past experience to COVID-19, which is a disease unlike any other seen during the LT era: a profound inflammatory phase mediated by a cytokine storm as the etiologic basis for the organ dysfunction, activation of coagulation pathways in pulmonary circulation leading to immunothrombosis contributing to the refractory hypoxemia, favorable effects of anticoagulants, diverse pulmonary physiologic phenotypes of ARDS, an increased risk of pleural complications, and utilization of novel anti-inflammatory therapies with consequent risks ofsecondary infections are all unique to COVID-19. A recent study found that patients requiring ECMO for COVID-19 ARDS took longer to recover lung function but had similar survival rates to patients on ECMO with other virus-induced ARDS (Raff LA, et al. Am J Surg. 2021;S0002-9610[21]00233-6. doi: 10.1016/j.amjsurg.2021.04.004. Online ahead of print).These data support pursuing a more conservative timeline for consideration of LT.
Determining the reversibility of pulmonary impairment in COVID-19 ARDS is another challenge. The nature of the pulmonary opacities should be assessed on CT scan imaging as close as possible to the time of LT consideration. Differentiating the extent of irreversible parenchymal scarring vs salvageability during acute illness can be challenging. The presence of extensive architectural distortion with or without bullous changes, while being the best indicator of irreversibility, may not be sensitive enough. The standard of care in such situations remains serial assessments, often weekly, by a dedicated multidisciplinary group. We have found it useful to augment the imaging data with pulmonary physiologic assessments, including the extent of ventilator and ECMO support as well as dynamic and static compliance trends. Improvement in physiologic data often precedes radiologic improvement. Nonetheless, an important area of future research is to identify objective markers for determining reversibility, which could include novel biomarkers in serum or bronchoalveolar lavage fluid.
When a determination is made regarding the irreversibility of pulmonary impairment, the LT evaluation should begin promptly. Pre-transplant deconditioning and debility is associated with worse post-transplant outcomes. In this regard, patients managed using an ambulatory ECMO strategy may have superior rehabilitation potential. Furthermore, an attempt should be made during the evaluation to wean sedation in order to facilitate discussions regarding the rigors of LT with the patient alongside present family members. An additional consideration, given the use of immunomodulatory medications for COVID-19 and prolonged intubation, is the dramatically increased risk of multi-drug resistant infections in this population; these must be aggressively managed for patients to remain eligible for LT.
The degree of pulmonary impairment and frequent colonization of the airways will likely dictate bilateral LT as the preferred strategy, although surgical feasibility may, at times, be the overriding determinant. Regardless of the type of transplant, certain unique aspects should be anticipated. The inflammatory responses during COVID-19 that often spill outside the confines of the pulmonary parenchyma, along with potentially frequent thoracic interventions prior to transplant, create significant technical challenges during the operation. Native pneumonectomy can take longer than usual leading to prolonged ischemic time, increased need for intra-operative blood products, and raised risk for primary graft dysfunction. All of these factors have a significant impact on early and late outcomes. Finally, the long-term immunologic consequences of severe infection from a novel virus remain unknown, and it is unclear if COVID-19 ARDS patients bridged to transplant will enjoy comparable survival. It is pertinent to acknowledge that the high-risk nature of such transplants is substantially accentuated due to several unique characteristics of the illness related to COVID-19.
The emergence of the COVID-19 pandemic has led to an increase in the number of urgent inpatient lung transplant consultations for refractory ARDS. While the basic principles of LT candidate selection should continue to guide us, the unique characteristics of this illness merit using a customized approach. There are few validated predictors to guide decision-making, and longitudinal assessments by a dedicated multidisciplinary group remain the best strategy. Finally, in the absence of systemic studies and lack of longitudinal outcomes data, there is an emergent need to establish consensus guidelines regarding the approach to LT consideration in these patients.
Dr. Quinn and Dr. Banga are with the Lung Transplant Program, Divisions of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas.
This month in the journal CHEST®
Editor’s picks
How I do it: Transitioning asthma care from adolescents to adults: Severe Asthma Series. By Dr. A. Nanzer.
Outpatient management of patients with COVID-19: Multicenter prospective validation of the HOME-CoV Rule to safely discharge patients. By Dr. D. Douillet, et al.
Emphysema progression and lung function decline among angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockade (ARB) users in the COPDGene Cohort. By Dr. V. Tejwani, et al.
Sarcoidosis: An occupational disease? By Dr. C.L. Oliver, et al.
Pulmonary thrombosis and thromboembolism in COVID-19. By Dr. H. Poor.
How I do it: Mediastinal staging for lung cancer. By Dr. F. Farjah, et al.
Editor’s picks
Editor’s picks
How I do it: Transitioning asthma care from adolescents to adults: Severe Asthma Series. By Dr. A. Nanzer.
Outpatient management of patients with COVID-19: Multicenter prospective validation of the HOME-CoV Rule to safely discharge patients. By Dr. D. Douillet, et al.
Emphysema progression and lung function decline among angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockade (ARB) users in the COPDGene Cohort. By Dr. V. Tejwani, et al.
Sarcoidosis: An occupational disease? By Dr. C.L. Oliver, et al.
Pulmonary thrombosis and thromboembolism in COVID-19. By Dr. H. Poor.
How I do it: Mediastinal staging for lung cancer. By Dr. F. Farjah, et al.
How I do it: Transitioning asthma care from adolescents to adults: Severe Asthma Series. By Dr. A. Nanzer.
Outpatient management of patients with COVID-19: Multicenter prospective validation of the HOME-CoV Rule to safely discharge patients. By Dr. D. Douillet, et al.
Emphysema progression and lung function decline among angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockade (ARB) users in the COPDGene Cohort. By Dr. V. Tejwani, et al.
Sarcoidosis: An occupational disease? By Dr. C.L. Oliver, et al.
Pulmonary thrombosis and thromboembolism in COVID-19. By Dr. H. Poor.
How I do it: Mediastinal staging for lung cancer. By Dr. F. Farjah, et al.
Rivaroxaban’s single daily dose may lead to higher bleeding risk than other DOACs
The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.
DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.
These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,
Daily dosage may exacerbate risk
Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.
Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.
Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.
The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.
Overall, the study cohort was small, compared with previous registry studies.
Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
Clinicians should consider location of bleeding
Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.
“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.
“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
Other studies yield similar results
Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.
Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.
A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.
“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.
“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.
The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.
The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.
DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.
These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,
Daily dosage may exacerbate risk
Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.
Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.
Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.
The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.
Overall, the study cohort was small, compared with previous registry studies.
Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
Clinicians should consider location of bleeding
Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.
“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.
“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
Other studies yield similar results
Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.
Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.
A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.
“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.
“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.
The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.
The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.
DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.
These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,
Daily dosage may exacerbate risk
Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.
Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.
Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.
The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.
Overall, the study cohort was small, compared with previous registry studies.
Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
Clinicians should consider location of bleeding
Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.
“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.
“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
Other studies yield similar results
Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.
Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.
A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.
“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.
“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.
The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.
FROM ANNALS OF INTERNAL MEDICINE
Family violence patterns change during pandemic
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Among adolescents treated for injuries caused by family-member violence, the proportion of incidents that involved illegal drugs or weapons more than doubled during the pandemic, and incidents that involved alcohol nearly doubled, according to data presented October 10 at the American Academy of Pediatrics 2021 National Conference.
“The COVID-19 pandemic amplified risk factors known to increase family interpersonal violence, such as increased need for parental supervision, parental stress, financial hardship, poor mental health, and isolation,” said investigator Mattea Miller, an MD candidate at the Johns Hopkins University School of Medicine, Baltimore.
To examine the issue, she and her colleagues “sought to characterize the prevalence and circumstances of adolescent injuries resulting from family interpersonal violence,” Ms. Miller told this news organization.
Their retrospective analysis involved children 10 to 15 years of age seen before or during the pandemic in the emergency department at Johns Hopkins Children’s Center for injuries that resulted from a violent incident with a family member.
Of the 819 incidents of violence-related injuries seen during the study period – the prepandemic ran from Jan. 1, 2019 to March 29, 2020, and the pandemic period ran from March 30, 2020, the date a stay-at-home order was first issued in Maryland, to Dec. 31, 2020 – 448 (54.7%) involved a family member. The proportion of such injuries was similar before and during the pandemic (54.6% vs. 54.9%; P = .99).
Most (83.9%) of these incidents occurred at home, 76.6% involved a parent or guardian, and 66.7% involved the youth being transported to the hospital by police.
It is surprising that families accounted for such a high level of violence involving adolescents, said Christopher S. Greeley, MD, MS, chief of the division of public health pediatrics at Texas Children’s Hospital and professor of pediatrics at Baylor College of Medicine, Houston, who was not involved in the research.
“The most common source of child physical abuse in younger children – infants and toddlers – [is the] parents,” who account for about 75% of cases, “but to see that amount of violence in adolescents was unexpected,” he told this news organization.
Patients in the study cohort were more likely to be Black than the hospital’s overall emergency-department population (84.4% vs. 60.0%), and more likely to be covered by public insurance (71.2% vs. 60.0%).
In the study cohort, 54.0% of the patients were female.
“We were surprised to see that 8% of visits did not have a referral to a social worker” – 92% of patients in the study cohort received a social work consult during their visit to the emergency department – and that number “did not vary during the COVID-19 pandemic,” Ms. Miller said. The pandemic exacerbated the types of stresses that social workers can help address, so “this potentially represents a gap in care that is important to address,” she added.
Increase in use of alcohol, drugs, weapons
The most significant increases from the prepandemic period to the pandemic period were in incidents that involved alcohol (10.0% vs. 18.8%; P ≤ .001), illegal drugs (6.5% vs. 14.9%; P ≤ .001), and weapons, most often a knife (10.7% vs. 23.8%; P ≤ .001).
“An obvious potential explanation for the increase in alcohol, drug, and weapons [involvement] would be the mental health impact of the pandemic in conjunction with the economic stressors that some families may be feeling,” Dr. Greeley said. Teachers are the most common reporters of child abuse, so it’s possible that reports of violence decreased when schools switched to remote learning. But with most schools back to in-person learning, data have not yet shown a surge in reporting, he noted.
The “epidemiology of family violence may be impacted by increased time at home, disruptions in school and family routines, exacerbations in mental health conditions, and financial stresses common during the pandemic,” said senior study investigator Leticia Ryan, MD, MPH, director of research in pediatrics at Johns Hopkins Medicine.
And research has shown increases in the use of alcohol and illegal drugs during the pandemic, she noted.
“As we transition to postpandemic life, it will be important to identify at-risk adolescents and families and provide supports,” Dr. Ryan told this news organization. “The emergency department is an appropriate setting to intervene with youth who have experienced family violence and initiate preventive strategies to avoid future violence.”
Among the strategies to identify and intervene for at-risk patients is the CRAFFT substance use screening tool. Furthermore, “case management, involvement of child protection services, and linkage with relevant support services may all be appropriate, depending on circumstances,” Ms. Miller added.
“Exposure to family violence at a young age increases the likelihood that a child will be exposed to additional violence or become a perpetrator of violence in the future, continuing a cycle of violence,” Ms. Miller explained. “Given that studies of adolescent violence often focus on peer violence, a better understanding of the epidemiology of violence-related injuries resulting from family violence is needed to better inform the development of more comprehensive prevention strategies.”
This study did not note any external funding. Ms. Miller, Dr. Greeley, and Dr. Ryan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New reports help nail down myocarditis risk with COVID-19 vaccine
Recent literature features new descriptions of myocarditis linked to the two available mRNA vaccines against SARS-CoV-2. They tell a story largely consistent with experience to date, and support what might be its most useful public health message: The associated myocarditis is usually mild and self-limiting, and is far less likely to occur than myocarditis or death in unvaccinated people with COVID-19.
In line with previous research, the new analyses suggest the myocarditis – with onset usually a few days to a week after injection – has an overall incidence that ranges from less than 1 to perhaps 3 per 100,000 people who received at least one of the full mRNA-vaccine regimen’s two injections. Also, as in earlier studies, the incidence climbed higher – sometimes sharply – in certain groups by age and sex, particularly in young men and older male teens.
The new studies “are confirmatory, in terms of the risk being low,” but underscore that clinicians still must be wary of myocarditis as a potential complication of the mRNA vaccines, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, told this news organization.
Dr. Bozkurt, a leading heart failure specialist and researcher, did not contribute to any of the new reports but does study the myocarditis of COVID-19 and was lead author on a recent review of the potential vaccine complication’s features and possible mechanisms.
In the new myocarditis reports, she observed, more than 90% of the cases were mild and “resolved on their own without a major adverse outcome.” Dr. Bozkurt emphasized the need for perspective regarding the risk. For example, the myocarditis associated with SARS-CoV-2 infection is not only more likely than the vaccine-related myocarditis, but it’s also usually far more severe.
Dr. Bozkurt pointed to a recent study in which the mRNA vaccines, compared with no vaccination, appeared to escalate the myocarditis risk by a factor of 3, whereas the risk for myocarditis in SARS-CoV-2 infection was increased 18 times.
In contrast, she observed, the new myocarditis cases reported this week feature a few that are novel or are at least very rare, including the case of a patient who developed cardiogenic shock and another with fulminant myocarditis who died.
The Centers for Disease Control and Prevention in May publicly described the apparent link between myocarditis and the two available mRNA vaccines against SARS-CoV-2: BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). The next month, the Food and Drug Administration added a warning about the risk to the labeling.
Less than 1 case per 100,000
Fifteen confirmed cases of myocarditis were identified among about 2.4 million members of Kaiser Permanente Southern California aged 18 or older who received at least one injection of the Pfizer or Moderna mRNA vaccines between December 2020 and July 2021, in a report published in JAMA Internal Medicine. The study counted cases up to 10 days after the first or second injection, of which there were 2 and 13, respectively.
All eight patients who received the Pfizer BNT162b2 vaccine and the eight given the Moderna mRNA-1273 vaccine were male with a median age of 25 years (interquartile range, 20-32 years).
“The main takeaway messages from our study are that the incidence of myocarditis after COVID-19 mRNA vaccinations is very low, that this condition is primarily observed in young men within a few days after the second dose, and that most patients recover quickly,” senior author Mingsum Lee, MD, PhD, Kaiser Permanente Los Angeles Medical Center, told this news organization.
“The incidence of vaccine-related myocarditis was significantly lower than rates of COVID-19 hospitalization during the same period and population area,” she added.
The group saw a per-million incidence of 0.8 and 5.8 myocarditis cases in the 10 days after first and second injections, respectively. That made for an incidence of 0.58 per 100,000, or 1 case per 172,414 fully vaccinated adults.
The group also considered a cohort of 1,577,741 unvaccinated people with a median age of 39 years (interquartile range, 28-53 years) during the same period. Of the 75 cases of myocarditis, 52% were in men, they reported.
Comparing the vaccinated and unvaccinated cohorts, they saw a 10-day vaccine-associated myocarditis incidence rate ratio of 0.38 (95% confidence interval, 0.05-1.40; P = .15) after the first dose, and 2.7 (95% CI, 1.4-4.8; P = .004) after the second dose.
In a comparison of the vaccinated group with itself using data from a 10-day period in the previous year, the corresponding myocarditis IRRs were 1.0 (P > .99) and 3.3 (P = .03), respectively.
Dr. Lee said none of the 15 patients required admission to an intensive care unit. “All patients with myocarditis responded well to treatment and felt better quickly,” she noted.
Myocarditis after an mRNA vaccine injection is rare and, Dr. Lee said emphatically, and “the benefits of the COVID-19 vaccine greatly outweigh the risks.”
Sex- and age-stratified rates
In a separate analysis of 5,442,696 people given a first dose of the Pfizer BNT162b2 vaccine and 5,125,635 given a second dose, there were 142 cases of myocarditis with onset 21 days after dose 1 and 30 days after dose 2. Of those cases, 136 were documented as “definite or probable” in an Israeli Ministry of Health database that covered up to the end of May 2021.
There were also 40 cases among vaccinated people seen after the 30-day window, which were considered not related to the vaccination, and 101 cases among unvaccinated people; of the latter, 29 had confirmed diagnoses of COVID-19.
Of the 136 people with definite or probable cases, the myocarditis was “generally mild” in 129 and usually resolved on its own, notes the report on the study, published in the New England Journal of Medicine, with lead author Dror Mevorach, MD, Hadassah-Hebrew University Medical Center, Jerusalem.
The estimated myocarditis incidence after a second such vaccine dose across the entire Israeli population, based on the current study, was about one per 26,000 males and one per 218,000 females, the group writes. Those figures compare with one case per 10,857 among “the general unvaccinated population.”
Again, the risk was concentrated among younger men and male adolescents. In an analysis limited to vaccinated people aged 16-19 years, myocarditis in the 21 days after a second mRNA injection was seen in about one of 6,637 males and one of 99,853 females, the group reported.
The standardized incidence ratio of 5.34 (95% CI, 4.48-6.40) after a second injection, across all groups, “was driven mostly by the diagnosis of myocarditis in younger male recipients.” Among that male subgroup, the ratios by age group were 13.60 (95% CI, 9.30-19.20) for 16-19 years, 8.53 (95% CI, 5.57-12.50) for 20-24 years, and 6.96 (95% CI, 4.25-10.75) for 25-29 years.
Among people who received a second injection, compared with unvaccinated people, the 30-day rate ratio was 2.35 (95% CI, 1.10-5.02). Again, the effect was concentrated in males aged 16-19 years. Among them, the myocarditis rate ratios in the 30 days after a second mRNA vaccine injection were 8.96 (95% CI, 4.50-17.83) for the 16-19 years group, 6.13 (95% CI, 3.16-11.88) for the 20-24 group, and 3.58 (95% CI, 1.82-7.01) for 25-29 years.
Most of the patients with myocarditis showed “significant clinical improvement,” with a mean hospitalization time of only 3-4 days, the report notes. Treatment consisted of nonsteroidal anti-inflammatory drugs “with or without colchicine for presumed pericardial inflammation.”
However, seven patients (4.9%) developed important complications, including left-ventricular dysfunction, ventricular arrhythmias, and heart failure. Among them was a 22-year-old patient who died of fulminant myocarditis within 24 hours of diagnosis, the group wrote.
From an Israeli health care organization
Published by the same journal as the study by Dr. Menvorach and associates, an analysis of a separate database showed largely consistent findings among patients in the largest of Israel’s four health care organizations charged by the government to administer health services.
The report, with authors led by Guy Witberg, MD, Rabin Medical Center, Petah Tikva, Israel, focused on members of the health care organization aged 16 years or older who had received at least one Pfizer mRNA vaccine dose by the end of May 2021.
The cohorts from the two separate reports surely overlap substantially, as the Ministry of Health analysis from Dr. Mevorach and colleagues derived from a nationwide database, and – as Dr. Witberg and associates wrote – the health care organization providing their data covers 52% of the Israeli population.
Of 2,558,421 vaccinated people in the analysis, of whom 94% received two doses, 54 developed confirmed myocarditis in the 42 days after the first dose. Their median age was 27 years (interquartile range, 21-35 years) and all but three (94%) were male. Of those 54 cases, 41 were considered mild and 12 intermediate in severity, and one was fulminant with the patient in cardiogenic shock, the group writes. In addition, nonsustained ventricular tachycardia and atrial fibrillation developed in 5% and 3% of cases, respectively.
The estimated myocarditis incidence in the 42 days after administration of at least one mRNA vaccine dose was 2.13 per 100,000 vaccinated people. In that group, Dr. Witberg and colleagues note, the corresponding incidences per 100,000 were 4.12 and 0.23 for males and females, respectively.
Also in the current report, incidences per 100,000 vaccinated people aged 16-29 years, by sex, included 5.49 (95% CI, 3.59-7.39) overall, and 10.69 (95% CI, 6.93-14.46) for males (the highest rate in the report).
There was only one case in a female aged 16-29 years, and two cases in females 30 years or older.
Of note, some authors of the current study are also authors on the high-profile report from Noam Barda, MD, and colleagues published in the New England Journal of Medicine, that used the same database to arrive at an mRNA-vaccine-related incidence of myocarditis of 2.7 per 100,000. Eligibility criteria and follow-up time were different in that report, as were case ascertainment criteria.
The myocarditis risk associated with the two mRNA vaccines is small compared with “the morbidity and mortality of COVID-19 infection, in which up to 28% of hospitalized patients showed signs of myocardial injury,” wrote Vinay Guduguntla, MD, University of California, San Francisco, and Mitchell H. Katz, MD, NYC Health + Hospitals, New York, in an editorial accompanying the report from Dr. Lee and associates.
“Randomized clinical trials show that COVID-19 mRNA vaccines represent a safe and effective method of preventing infection,” they stated. “The identification of rare myocarditis does not change clinical decision-making.”
Dr. Bozkurt, who is immediate past president of the Heart Failure Society of America, has disclosed consulting for Bayer and scPharmaceuticals and serving on a clinical events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. Lee and the report’s other authors had no disclosures. Dr. Mevorach discloses consulting for Enlivex Therapeutics; disclosures for the other authors are available at NEJM.org. Dr. Witberg said he has no interests to disclose; disclosures for the other authors are available at NEJM.org. Dr. Guduguntla is an editorial fellow and Dr. Katz a deputy editor at JAMA Internal Medicine; neither had disclosures.
A version of this article first appeared on Medscape.com.
Recent literature features new descriptions of myocarditis linked to the two available mRNA vaccines against SARS-CoV-2. They tell a story largely consistent with experience to date, and support what might be its most useful public health message: The associated myocarditis is usually mild and self-limiting, and is far less likely to occur than myocarditis or death in unvaccinated people with COVID-19.
In line with previous research, the new analyses suggest the myocarditis – with onset usually a few days to a week after injection – has an overall incidence that ranges from less than 1 to perhaps 3 per 100,000 people who received at least one of the full mRNA-vaccine regimen’s two injections. Also, as in earlier studies, the incidence climbed higher – sometimes sharply – in certain groups by age and sex, particularly in young men and older male teens.
The new studies “are confirmatory, in terms of the risk being low,” but underscore that clinicians still must be wary of myocarditis as a potential complication of the mRNA vaccines, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, told this news organization.
Dr. Bozkurt, a leading heart failure specialist and researcher, did not contribute to any of the new reports but does study the myocarditis of COVID-19 and was lead author on a recent review of the potential vaccine complication’s features and possible mechanisms.
In the new myocarditis reports, she observed, more than 90% of the cases were mild and “resolved on their own without a major adverse outcome.” Dr. Bozkurt emphasized the need for perspective regarding the risk. For example, the myocarditis associated with SARS-CoV-2 infection is not only more likely than the vaccine-related myocarditis, but it’s also usually far more severe.
Dr. Bozkurt pointed to a recent study in which the mRNA vaccines, compared with no vaccination, appeared to escalate the myocarditis risk by a factor of 3, whereas the risk for myocarditis in SARS-CoV-2 infection was increased 18 times.
In contrast, she observed, the new myocarditis cases reported this week feature a few that are novel or are at least very rare, including the case of a patient who developed cardiogenic shock and another with fulminant myocarditis who died.
The Centers for Disease Control and Prevention in May publicly described the apparent link between myocarditis and the two available mRNA vaccines against SARS-CoV-2: BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). The next month, the Food and Drug Administration added a warning about the risk to the labeling.
Less than 1 case per 100,000
Fifteen confirmed cases of myocarditis were identified among about 2.4 million members of Kaiser Permanente Southern California aged 18 or older who received at least one injection of the Pfizer or Moderna mRNA vaccines between December 2020 and July 2021, in a report published in JAMA Internal Medicine. The study counted cases up to 10 days after the first or second injection, of which there were 2 and 13, respectively.
All eight patients who received the Pfizer BNT162b2 vaccine and the eight given the Moderna mRNA-1273 vaccine were male with a median age of 25 years (interquartile range, 20-32 years).
“The main takeaway messages from our study are that the incidence of myocarditis after COVID-19 mRNA vaccinations is very low, that this condition is primarily observed in young men within a few days after the second dose, and that most patients recover quickly,” senior author Mingsum Lee, MD, PhD, Kaiser Permanente Los Angeles Medical Center, told this news organization.
“The incidence of vaccine-related myocarditis was significantly lower than rates of COVID-19 hospitalization during the same period and population area,” she added.
The group saw a per-million incidence of 0.8 and 5.8 myocarditis cases in the 10 days after first and second injections, respectively. That made for an incidence of 0.58 per 100,000, or 1 case per 172,414 fully vaccinated adults.
The group also considered a cohort of 1,577,741 unvaccinated people with a median age of 39 years (interquartile range, 28-53 years) during the same period. Of the 75 cases of myocarditis, 52% were in men, they reported.
Comparing the vaccinated and unvaccinated cohorts, they saw a 10-day vaccine-associated myocarditis incidence rate ratio of 0.38 (95% confidence interval, 0.05-1.40; P = .15) after the first dose, and 2.7 (95% CI, 1.4-4.8; P = .004) after the second dose.
In a comparison of the vaccinated group with itself using data from a 10-day period in the previous year, the corresponding myocarditis IRRs were 1.0 (P > .99) and 3.3 (P = .03), respectively.
Dr. Lee said none of the 15 patients required admission to an intensive care unit. “All patients with myocarditis responded well to treatment and felt better quickly,” she noted.
Myocarditis after an mRNA vaccine injection is rare and, Dr. Lee said emphatically, and “the benefits of the COVID-19 vaccine greatly outweigh the risks.”
Sex- and age-stratified rates
In a separate analysis of 5,442,696 people given a first dose of the Pfizer BNT162b2 vaccine and 5,125,635 given a second dose, there were 142 cases of myocarditis with onset 21 days after dose 1 and 30 days after dose 2. Of those cases, 136 were documented as “definite or probable” in an Israeli Ministry of Health database that covered up to the end of May 2021.
There were also 40 cases among vaccinated people seen after the 30-day window, which were considered not related to the vaccination, and 101 cases among unvaccinated people; of the latter, 29 had confirmed diagnoses of COVID-19.
Of the 136 people with definite or probable cases, the myocarditis was “generally mild” in 129 and usually resolved on its own, notes the report on the study, published in the New England Journal of Medicine, with lead author Dror Mevorach, MD, Hadassah-Hebrew University Medical Center, Jerusalem.
The estimated myocarditis incidence after a second such vaccine dose across the entire Israeli population, based on the current study, was about one per 26,000 males and one per 218,000 females, the group writes. Those figures compare with one case per 10,857 among “the general unvaccinated population.”
Again, the risk was concentrated among younger men and male adolescents. In an analysis limited to vaccinated people aged 16-19 years, myocarditis in the 21 days after a second mRNA injection was seen in about one of 6,637 males and one of 99,853 females, the group reported.
The standardized incidence ratio of 5.34 (95% CI, 4.48-6.40) after a second injection, across all groups, “was driven mostly by the diagnosis of myocarditis in younger male recipients.” Among that male subgroup, the ratios by age group were 13.60 (95% CI, 9.30-19.20) for 16-19 years, 8.53 (95% CI, 5.57-12.50) for 20-24 years, and 6.96 (95% CI, 4.25-10.75) for 25-29 years.
Among people who received a second injection, compared with unvaccinated people, the 30-day rate ratio was 2.35 (95% CI, 1.10-5.02). Again, the effect was concentrated in males aged 16-19 years. Among them, the myocarditis rate ratios in the 30 days after a second mRNA vaccine injection were 8.96 (95% CI, 4.50-17.83) for the 16-19 years group, 6.13 (95% CI, 3.16-11.88) for the 20-24 group, and 3.58 (95% CI, 1.82-7.01) for 25-29 years.
Most of the patients with myocarditis showed “significant clinical improvement,” with a mean hospitalization time of only 3-4 days, the report notes. Treatment consisted of nonsteroidal anti-inflammatory drugs “with or without colchicine for presumed pericardial inflammation.”
However, seven patients (4.9%) developed important complications, including left-ventricular dysfunction, ventricular arrhythmias, and heart failure. Among them was a 22-year-old patient who died of fulminant myocarditis within 24 hours of diagnosis, the group wrote.
From an Israeli health care organization
Published by the same journal as the study by Dr. Menvorach and associates, an analysis of a separate database showed largely consistent findings among patients in the largest of Israel’s four health care organizations charged by the government to administer health services.
The report, with authors led by Guy Witberg, MD, Rabin Medical Center, Petah Tikva, Israel, focused on members of the health care organization aged 16 years or older who had received at least one Pfizer mRNA vaccine dose by the end of May 2021.
The cohorts from the two separate reports surely overlap substantially, as the Ministry of Health analysis from Dr. Mevorach and colleagues derived from a nationwide database, and – as Dr. Witberg and associates wrote – the health care organization providing their data covers 52% of the Israeli population.
Of 2,558,421 vaccinated people in the analysis, of whom 94% received two doses, 54 developed confirmed myocarditis in the 42 days after the first dose. Their median age was 27 years (interquartile range, 21-35 years) and all but three (94%) were male. Of those 54 cases, 41 were considered mild and 12 intermediate in severity, and one was fulminant with the patient in cardiogenic shock, the group writes. In addition, nonsustained ventricular tachycardia and atrial fibrillation developed in 5% and 3% of cases, respectively.
The estimated myocarditis incidence in the 42 days after administration of at least one mRNA vaccine dose was 2.13 per 100,000 vaccinated people. In that group, Dr. Witberg and colleagues note, the corresponding incidences per 100,000 were 4.12 and 0.23 for males and females, respectively.
Also in the current report, incidences per 100,000 vaccinated people aged 16-29 years, by sex, included 5.49 (95% CI, 3.59-7.39) overall, and 10.69 (95% CI, 6.93-14.46) for males (the highest rate in the report).
There was only one case in a female aged 16-29 years, and two cases in females 30 years or older.
Of note, some authors of the current study are also authors on the high-profile report from Noam Barda, MD, and colleagues published in the New England Journal of Medicine, that used the same database to arrive at an mRNA-vaccine-related incidence of myocarditis of 2.7 per 100,000. Eligibility criteria and follow-up time were different in that report, as were case ascertainment criteria.
The myocarditis risk associated with the two mRNA vaccines is small compared with “the morbidity and mortality of COVID-19 infection, in which up to 28% of hospitalized patients showed signs of myocardial injury,” wrote Vinay Guduguntla, MD, University of California, San Francisco, and Mitchell H. Katz, MD, NYC Health + Hospitals, New York, in an editorial accompanying the report from Dr. Lee and associates.
“Randomized clinical trials show that COVID-19 mRNA vaccines represent a safe and effective method of preventing infection,” they stated. “The identification of rare myocarditis does not change clinical decision-making.”
Dr. Bozkurt, who is immediate past president of the Heart Failure Society of America, has disclosed consulting for Bayer and scPharmaceuticals and serving on a clinical events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. Lee and the report’s other authors had no disclosures. Dr. Mevorach discloses consulting for Enlivex Therapeutics; disclosures for the other authors are available at NEJM.org. Dr. Witberg said he has no interests to disclose; disclosures for the other authors are available at NEJM.org. Dr. Guduguntla is an editorial fellow and Dr. Katz a deputy editor at JAMA Internal Medicine; neither had disclosures.
A version of this article first appeared on Medscape.com.
Recent literature features new descriptions of myocarditis linked to the two available mRNA vaccines against SARS-CoV-2. They tell a story largely consistent with experience to date, and support what might be its most useful public health message: The associated myocarditis is usually mild and self-limiting, and is far less likely to occur than myocarditis or death in unvaccinated people with COVID-19.
In line with previous research, the new analyses suggest the myocarditis – with onset usually a few days to a week after injection – has an overall incidence that ranges from less than 1 to perhaps 3 per 100,000 people who received at least one of the full mRNA-vaccine regimen’s two injections. Also, as in earlier studies, the incidence climbed higher – sometimes sharply – in certain groups by age and sex, particularly in young men and older male teens.
The new studies “are confirmatory, in terms of the risk being low,” but underscore that clinicians still must be wary of myocarditis as a potential complication of the mRNA vaccines, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, told this news organization.
Dr. Bozkurt, a leading heart failure specialist and researcher, did not contribute to any of the new reports but does study the myocarditis of COVID-19 and was lead author on a recent review of the potential vaccine complication’s features and possible mechanisms.
In the new myocarditis reports, she observed, more than 90% of the cases were mild and “resolved on their own without a major adverse outcome.” Dr. Bozkurt emphasized the need for perspective regarding the risk. For example, the myocarditis associated with SARS-CoV-2 infection is not only more likely than the vaccine-related myocarditis, but it’s also usually far more severe.
Dr. Bozkurt pointed to a recent study in which the mRNA vaccines, compared with no vaccination, appeared to escalate the myocarditis risk by a factor of 3, whereas the risk for myocarditis in SARS-CoV-2 infection was increased 18 times.
In contrast, she observed, the new myocarditis cases reported this week feature a few that are novel or are at least very rare, including the case of a patient who developed cardiogenic shock and another with fulminant myocarditis who died.
The Centers for Disease Control and Prevention in May publicly described the apparent link between myocarditis and the two available mRNA vaccines against SARS-CoV-2: BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). The next month, the Food and Drug Administration added a warning about the risk to the labeling.
Less than 1 case per 100,000
Fifteen confirmed cases of myocarditis were identified among about 2.4 million members of Kaiser Permanente Southern California aged 18 or older who received at least one injection of the Pfizer or Moderna mRNA vaccines between December 2020 and July 2021, in a report published in JAMA Internal Medicine. The study counted cases up to 10 days after the first or second injection, of which there were 2 and 13, respectively.
All eight patients who received the Pfizer BNT162b2 vaccine and the eight given the Moderna mRNA-1273 vaccine were male with a median age of 25 years (interquartile range, 20-32 years).
“The main takeaway messages from our study are that the incidence of myocarditis after COVID-19 mRNA vaccinations is very low, that this condition is primarily observed in young men within a few days after the second dose, and that most patients recover quickly,” senior author Mingsum Lee, MD, PhD, Kaiser Permanente Los Angeles Medical Center, told this news organization.
“The incidence of vaccine-related myocarditis was significantly lower than rates of COVID-19 hospitalization during the same period and population area,” she added.
The group saw a per-million incidence of 0.8 and 5.8 myocarditis cases in the 10 days after first and second injections, respectively. That made for an incidence of 0.58 per 100,000, or 1 case per 172,414 fully vaccinated adults.
The group also considered a cohort of 1,577,741 unvaccinated people with a median age of 39 years (interquartile range, 28-53 years) during the same period. Of the 75 cases of myocarditis, 52% were in men, they reported.
Comparing the vaccinated and unvaccinated cohorts, they saw a 10-day vaccine-associated myocarditis incidence rate ratio of 0.38 (95% confidence interval, 0.05-1.40; P = .15) after the first dose, and 2.7 (95% CI, 1.4-4.8; P = .004) after the second dose.
In a comparison of the vaccinated group with itself using data from a 10-day period in the previous year, the corresponding myocarditis IRRs were 1.0 (P > .99) and 3.3 (P = .03), respectively.
Dr. Lee said none of the 15 patients required admission to an intensive care unit. “All patients with myocarditis responded well to treatment and felt better quickly,” she noted.
Myocarditis after an mRNA vaccine injection is rare and, Dr. Lee said emphatically, and “the benefits of the COVID-19 vaccine greatly outweigh the risks.”
Sex- and age-stratified rates
In a separate analysis of 5,442,696 people given a first dose of the Pfizer BNT162b2 vaccine and 5,125,635 given a second dose, there were 142 cases of myocarditis with onset 21 days after dose 1 and 30 days after dose 2. Of those cases, 136 were documented as “definite or probable” in an Israeli Ministry of Health database that covered up to the end of May 2021.
There were also 40 cases among vaccinated people seen after the 30-day window, which were considered not related to the vaccination, and 101 cases among unvaccinated people; of the latter, 29 had confirmed diagnoses of COVID-19.
Of the 136 people with definite or probable cases, the myocarditis was “generally mild” in 129 and usually resolved on its own, notes the report on the study, published in the New England Journal of Medicine, with lead author Dror Mevorach, MD, Hadassah-Hebrew University Medical Center, Jerusalem.
The estimated myocarditis incidence after a second such vaccine dose across the entire Israeli population, based on the current study, was about one per 26,000 males and one per 218,000 females, the group writes. Those figures compare with one case per 10,857 among “the general unvaccinated population.”
Again, the risk was concentrated among younger men and male adolescents. In an analysis limited to vaccinated people aged 16-19 years, myocarditis in the 21 days after a second mRNA injection was seen in about one of 6,637 males and one of 99,853 females, the group reported.
The standardized incidence ratio of 5.34 (95% CI, 4.48-6.40) after a second injection, across all groups, “was driven mostly by the diagnosis of myocarditis in younger male recipients.” Among that male subgroup, the ratios by age group were 13.60 (95% CI, 9.30-19.20) for 16-19 years, 8.53 (95% CI, 5.57-12.50) for 20-24 years, and 6.96 (95% CI, 4.25-10.75) for 25-29 years.
Among people who received a second injection, compared with unvaccinated people, the 30-day rate ratio was 2.35 (95% CI, 1.10-5.02). Again, the effect was concentrated in males aged 16-19 years. Among them, the myocarditis rate ratios in the 30 days after a second mRNA vaccine injection were 8.96 (95% CI, 4.50-17.83) for the 16-19 years group, 6.13 (95% CI, 3.16-11.88) for the 20-24 group, and 3.58 (95% CI, 1.82-7.01) for 25-29 years.
Most of the patients with myocarditis showed “significant clinical improvement,” with a mean hospitalization time of only 3-4 days, the report notes. Treatment consisted of nonsteroidal anti-inflammatory drugs “with or without colchicine for presumed pericardial inflammation.”
However, seven patients (4.9%) developed important complications, including left-ventricular dysfunction, ventricular arrhythmias, and heart failure. Among them was a 22-year-old patient who died of fulminant myocarditis within 24 hours of diagnosis, the group wrote.
From an Israeli health care organization
Published by the same journal as the study by Dr. Menvorach and associates, an analysis of a separate database showed largely consistent findings among patients in the largest of Israel’s four health care organizations charged by the government to administer health services.
The report, with authors led by Guy Witberg, MD, Rabin Medical Center, Petah Tikva, Israel, focused on members of the health care organization aged 16 years or older who had received at least one Pfizer mRNA vaccine dose by the end of May 2021.
The cohorts from the two separate reports surely overlap substantially, as the Ministry of Health analysis from Dr. Mevorach and colleagues derived from a nationwide database, and – as Dr. Witberg and associates wrote – the health care organization providing their data covers 52% of the Israeli population.
Of 2,558,421 vaccinated people in the analysis, of whom 94% received two doses, 54 developed confirmed myocarditis in the 42 days after the first dose. Their median age was 27 years (interquartile range, 21-35 years) and all but three (94%) were male. Of those 54 cases, 41 were considered mild and 12 intermediate in severity, and one was fulminant with the patient in cardiogenic shock, the group writes. In addition, nonsustained ventricular tachycardia and atrial fibrillation developed in 5% and 3% of cases, respectively.
The estimated myocarditis incidence in the 42 days after administration of at least one mRNA vaccine dose was 2.13 per 100,000 vaccinated people. In that group, Dr. Witberg and colleagues note, the corresponding incidences per 100,000 were 4.12 and 0.23 for males and females, respectively.
Also in the current report, incidences per 100,000 vaccinated people aged 16-29 years, by sex, included 5.49 (95% CI, 3.59-7.39) overall, and 10.69 (95% CI, 6.93-14.46) for males (the highest rate in the report).
There was only one case in a female aged 16-29 years, and two cases in females 30 years or older.
Of note, some authors of the current study are also authors on the high-profile report from Noam Barda, MD, and colleagues published in the New England Journal of Medicine, that used the same database to arrive at an mRNA-vaccine-related incidence of myocarditis of 2.7 per 100,000. Eligibility criteria and follow-up time were different in that report, as were case ascertainment criteria.
The myocarditis risk associated with the two mRNA vaccines is small compared with “the morbidity and mortality of COVID-19 infection, in which up to 28% of hospitalized patients showed signs of myocardial injury,” wrote Vinay Guduguntla, MD, University of California, San Francisco, and Mitchell H. Katz, MD, NYC Health + Hospitals, New York, in an editorial accompanying the report from Dr. Lee and associates.
“Randomized clinical trials show that COVID-19 mRNA vaccines represent a safe and effective method of preventing infection,” they stated. “The identification of rare myocarditis does not change clinical decision-making.”
Dr. Bozkurt, who is immediate past president of the Heart Failure Society of America, has disclosed consulting for Bayer and scPharmaceuticals and serving on a clinical events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. Lee and the report’s other authors had no disclosures. Dr. Mevorach discloses consulting for Enlivex Therapeutics; disclosures for the other authors are available at NEJM.org. Dr. Witberg said he has no interests to disclose; disclosures for the other authors are available at NEJM.org. Dr. Guduguntla is an editorial fellow and Dr. Katz a deputy editor at JAMA Internal Medicine; neither had disclosures.
A version of this article first appeared on Medscape.com.