There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.

“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.

At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.

The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).

Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky

In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.

“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.

Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.

These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.

For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).

“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.

The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.

There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).

These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).

Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.

There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.

He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.

“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.

The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Power morcellators can be safely used for some gynecologic surgeries, according to recent guidance from the Food and Drug Administration, but doing so requires careful patient selection and use of a legally marketed tissue containment system.

The agency noted that physicians should conduct a thorough preoperative screening and that the devices should only be used for hysterectomies and myomectomies. Clinicians should not use the devices in cases involving uterine malignancy or suspected uterine malignancy.

In addition, clinicians should not use morcellators to remove uterine tissue containing suspected fibroids in women older than 50 years or who are postmenopausal. Nor should the devices be used for women who are “candidates for removal of tissue (en bloc) through the vagina or via a minilaparotomy incision,” the agency said.

The safety communication, which was issued on Dec. 29, 2020, updates previous guidance from February 2020. The updated recommendations are consistent with final labeling guidance for laparoscopic power morcellators, also issued by the FDA on Dec. 29.
 

Risk of disease spread

Prior evidence suggests that use of uncontained power morcellators in women with malignant uterine tissue can spread disease.

Even among women who do not have malignant uterine tissue, containment is important. The agency noted an association between uncontained power morcellation and the spread of benign uterine tissue, such as parasitic myomas and disseminated peritoneal leiomyomatosis, which could require additional surgeries.

In 2016, the FDA approved the PneumoLiner, a containment system for isolating uterine tissue that is not suspected of containing cancer.

“While unsuspected cancer can occur at any age, the prevalence of unsuspected cancer in women undergoing hysterectomy for fibroids increases with age such that the benefit-risk profile of using [laparoscopic power morcellators] is worse in older women when compared to younger women,” according to the new labeling guidance. “Also, the surgical technique of en bloc tissue removal eliminates the need to perform morcellation, thereby reducing the risk of iatrogenic dissemination and upstaging of an occult sarcoma. A thorough preoperative screening should be conducted; however, it is important to note that no screening procedure that can reliably detect sarcoma preoperatively has been identified.”

“The FDA will continue to review the latest data and scientific literature on laparoscopic power morcellation, including gathering real-world evidence from patients, providers and others, and encouraging innovation to better detect uterine cancer and develop containment systems for gynecologic surgery,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a news release. “The FDA seeks to ensure women and their health care providers are fully informed when considering laparoscopic power morcellators for gynecologic surgeries.”

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

Power morcellators can be safely used for some gynecologic surgeries, according to recent guidance from the Food and Drug Administration, but doing so requires careful patient selection and use of a legally marketed tissue containment system.

The agency noted that physicians should conduct a thorough preoperative screening and that the devices should only be used for hysterectomies and myomectomies. Clinicians should not use the devices in cases involving uterine malignancy or suspected uterine malignancy.

In addition, clinicians should not use morcellators to remove uterine tissue containing suspected fibroids in women older than 50 years or who are postmenopausal. Nor should the devices be used for women who are “candidates for removal of tissue (en bloc) through the vagina or via a minilaparotomy incision,” the agency said.

The safety communication, which was issued on Dec. 29, 2020, updates previous guidance from February 2020. The updated recommendations are consistent with final labeling guidance for laparoscopic power morcellators, also issued by the FDA on Dec. 29.
 

Risk of disease spread

Prior evidence suggests that use of uncontained power morcellators in women with malignant uterine tissue can spread disease.

Even among women who do not have malignant uterine tissue, containment is important. The agency noted an association between uncontained power morcellation and the spread of benign uterine tissue, such as parasitic myomas and disseminated peritoneal leiomyomatosis, which could require additional surgeries.

In 2016, the FDA approved the PneumoLiner, a containment system for isolating uterine tissue that is not suspected of containing cancer.

“While unsuspected cancer can occur at any age, the prevalence of unsuspected cancer in women undergoing hysterectomy for fibroids increases with age such that the benefit-risk profile of using [laparoscopic power morcellators] is worse in older women when compared to younger women,” according to the new labeling guidance. “Also, the surgical technique of en bloc tissue removal eliminates the need to perform morcellation, thereby reducing the risk of iatrogenic dissemination and upstaging of an occult sarcoma. A thorough preoperative screening should be conducted; however, it is important to note that no screening procedure that can reliably detect sarcoma preoperatively has been identified.”

“The FDA will continue to review the latest data and scientific literature on laparoscopic power morcellation, including gathering real-world evidence from patients, providers and others, and encouraging innovation to better detect uterine cancer and develop containment systems for gynecologic surgery,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a news release. “The FDA seeks to ensure women and their health care providers are fully informed when considering laparoscopic power morcellators for gynecologic surgeries.”

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

Power morcellators can be safely used for some gynecologic surgeries, according to recent guidance from the Food and Drug Administration, but doing so requires careful patient selection and use of a legally marketed tissue containment system.

The agency noted that physicians should conduct a thorough preoperative screening and that the devices should only be used for hysterectomies and myomectomies. Clinicians should not use the devices in cases involving uterine malignancy or suspected uterine malignancy.

In addition, clinicians should not use morcellators to remove uterine tissue containing suspected fibroids in women older than 50 years or who are postmenopausal. Nor should the devices be used for women who are “candidates for removal of tissue (en bloc) through the vagina or via a minilaparotomy incision,” the agency said.

The safety communication, which was issued on Dec. 29, 2020, updates previous guidance from February 2020. The updated recommendations are consistent with final labeling guidance for laparoscopic power morcellators, also issued by the FDA on Dec. 29.
 

Risk of disease spread

Prior evidence suggests that use of uncontained power morcellators in women with malignant uterine tissue can spread disease.

Even among women who do not have malignant uterine tissue, containment is important. The agency noted an association between uncontained power morcellation and the spread of benign uterine tissue, such as parasitic myomas and disseminated peritoneal leiomyomatosis, which could require additional surgeries.

In 2016, the FDA approved the PneumoLiner, a containment system for isolating uterine tissue that is not suspected of containing cancer.

“While unsuspected cancer can occur at any age, the prevalence of unsuspected cancer in women undergoing hysterectomy for fibroids increases with age such that the benefit-risk profile of using [laparoscopic power morcellators] is worse in older women when compared to younger women,” according to the new labeling guidance. “Also, the surgical technique of en bloc tissue removal eliminates the need to perform morcellation, thereby reducing the risk of iatrogenic dissemination and upstaging of an occult sarcoma. A thorough preoperative screening should be conducted; however, it is important to note that no screening procedure that can reliably detect sarcoma preoperatively has been identified.”

“The FDA will continue to review the latest data and scientific literature on laparoscopic power morcellation, including gathering real-world evidence from patients, providers and others, and encouraging innovation to better detect uterine cancer and develop containment systems for gynecologic surgery,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a news release. “The FDA seeks to ensure women and their health care providers are fully informed when considering laparoscopic power morcellators for gynecologic surgeries.”

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

There’s little doubt that the COVID-19 pandemic has been hard on many children and adolescents just as it has been difficult for adults. The disruption of routines, reduced contact with friends, concern over getting ill, and financial turmoil suffered by many families is exacting a toll on our mental health, as has been documented by a number of recent surveys and studies.^1,2

Quite understandably, concern about rising levels of anxiety and depression in youth prompts additional worries about suicide, the second leading cause of death in adolescents and young adults. In response, many organizations have rallied to provide additional resources to help prevent suicidal thinking and actions. Online mental health tips, support phone and text lines, and the availability of telemedicine have all been mobilized to help people cope and stay safe both physically and psychologically.

But what are the actual numbers when it comes to youth suicide during COVID-19? According to many headlines in the press, the statistics are grim and support many of distressing predictions that have been made. A December story in an Arizona newspaper, “With Teen Suicides on the Rise, Tucson Educators Struggle to Prioritize Mental Health,” described a 67% increase in teen suicides in 2020 compared with 2019 in one county.³ Another post from Psychology Today, “America is Facing a Teen Suicide Pandemic,” raised similar alarms.⁴ Concern over suicide has even been used politically to argue against restrictions that could reduce the spread of COVID-19 infections.

But despite this common perception shared by both health care professionals and the public, there actually is not evidence at this point that the COVID-19 pandemic has led to a broad spike in youth suicide deaths or attempts. A recent study published in the journal Pediatrics compared suicide screening results on youth presenting to emergency departments for any reason in 2020 to the same month in 2019.⁵ The authors found no consistent increases in reported suicidal ideation or suicide attempts with scattered elevations found in some months during 2020 compared with the previous year (including February 2020 before the pandemic really began) but not others. Internationally, newly analyzed data from 2020 with regard to suicide deaths have suggested “either no rise in suicide rates ... or a fall in the early months of the pandemic.” In my home and, admittedly small, state of Vermont, data from the Department of Health have shown 93 suicide deaths across all ages as of mid-November 2020 compared with a 5-year average of 96.

Why don’t the data match the headlines? There are a number of possibilities.

1. Suicide rates in youth were going up before the pandemic. As it takes time to verify and analyze data from large populations, many of the reports on suicide that have been published and released in 2020 summarize data from prior years. Without looking closely, a news organization can easily slap on a headline that implies that the data were obtained during the pandemic.

2. Fluctuations tend to occur from year to year. Thankfully, youth suicide remains rare (although not rare enough). With small numbers, regular variations from year to year can look huge in terms of percentages, especially if one doesn’t pull back and look at longer trends over time.

3. People are reaching out for mental health services. The public health message to access support and treatment for COVID 19–related mental health struggles appears to be having an effect, but this increased demand should not necessarily be viewed as a proxy for suicidal ideation and attempts.

While the understanding that we are not actually in the midst of a surge in COVID 19–related youth suicide is reassuring, it is important not to get complacent. Much of the data remains preliminary, and, even if these numbers hold up, there is no guarantee that things will continue this way, especially if the pandemic and it restrictions continue to drag on for many more months. And of course, whether or not the pandemic is making things significantly worse, youth suicide remains an enormous public health imperative with every one being a human tragedy.

It is also quite possible that more detailed analyses will eventually reveal a more complex association between youth suicide and COVID-19, with effects of the pandemic being realized regionally or more for some groups than others. Data from before the pandemic indicated, for example, that suicide rates are increasing more rapidly among African American youth compared with white children and adolescents.⁶ With the COVID-19 pandemic itself affecting disadvantaged communities more strongly, one could readily expect variable impacts in mental health related to race or socioeconomic status. A recent article voices these concerns for indigenous youth in Montana: a state with one of the highest per capita suicide rates in the country.⁷ The article notes, however, that the rate of suicide overall in Montana in 2020 is comparable to those of previous years.

Overall, pediatricians should not be needlessly panicked that the COVID-19 pandemic has sparked a surge in youth suicide. The data at this point simply don’t support that assertion despite many headlines to the contrary. At the same time, many children and adolescents are certainly struggling with the stresses the pandemic has created and continue to need our close monitoring and support.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine. Follow him on Twitter @PediPsych. His new book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood,” launches Feb. 1, 2021.

References

1. Copeland WE et al. Impact of COVID-19 pandemic on college student mental health and wellness. J Am Acad Child Adolesc Psychiatry. 2020;60(1):134-41. doi: 10.1016/j.jaac.2020.08.466.

2. Qiu J et al. A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen Psychiatry. 2020;33:e100213. doi: 10.1136/gpsych-2020-100213.

3. Dhmara K. With teen suicides on the rise, Tucson educators struggle to prioritize mental health. Tuscon.com. Dec. 27, 2020.

4. Chafouleas, SM. America is facing a suicide epidemic: New data confirm the urgency of confronting it now. Psychology Today blog. Sept. 4, 2020.

5. Hill RM et al. Suicide ideation and attempts in a pediatric emergency department before and after COVID-19. Pediatrics. 2020. doi: 10.1542/peds.2020-029280.

6. John A et al. Trends in suicide during the covid-19 pandemic. BMJ 2020;371:m4352. doi: 10.1136/bmj.m4352.

7. Reardon S. Health officials fear COVID-19 pandemic-related suicide spike among indigenous youth. Time Magazine. December 2020.

There’s little doubt that the COVID-19 pandemic has been hard on many children and adolescents just as it has been difficult for adults. The disruption of routines, reduced contact with friends, concern over getting ill, and financial turmoil suffered by many families is exacting a toll on our mental health, as has been documented by a number of recent surveys and studies.^1,2

Quite understandably, concern about rising levels of anxiety and depression in youth prompts additional worries about suicide, the second leading cause of death in adolescents and young adults. In response, many organizations have rallied to provide additional resources to help prevent suicidal thinking and actions. Online mental health tips, support phone and text lines, and the availability of telemedicine have all been mobilized to help people cope and stay safe both physically and psychologically.

But what are the actual numbers when it comes to youth suicide during COVID-19? According to many headlines in the press, the statistics are grim and support many of distressing predictions that have been made. A December story in an Arizona newspaper, “With Teen Suicides on the Rise, Tucson Educators Struggle to Prioritize Mental Health,” described a 67% increase in teen suicides in 2020 compared with 2019 in one county.³ Another post from Psychology Today, “America is Facing a Teen Suicide Pandemic,” raised similar alarms.⁴ Concern over suicide has even been used politically to argue against restrictions that could reduce the spread of COVID-19 infections.

But despite this common perception shared by both health care professionals and the public, there actually is not evidence at this point that the COVID-19 pandemic has led to a broad spike in youth suicide deaths or attempts. A recent study published in the journal Pediatrics compared suicide screening results on youth presenting to emergency departments for any reason in 2020 to the same month in 2019.⁵ The authors found no consistent increases in reported suicidal ideation or suicide attempts with scattered elevations found in some months during 2020 compared with the previous year (including February 2020 before the pandemic really began) but not others. Internationally, newly analyzed data from 2020 with regard to suicide deaths have suggested “either no rise in suicide rates ... or a fall in the early months of the pandemic.” In my home and, admittedly small, state of Vermont, data from the Department of Health have shown 93 suicide deaths across all ages as of mid-November 2020 compared with a 5-year average of 96.

Why don’t the data match the headlines? There are a number of possibilities.

1. Suicide rates in youth were going up before the pandemic. As it takes time to verify and analyze data from large populations, many of the reports on suicide that have been published and released in 2020 summarize data from prior years. Without looking closely, a news organization can easily slap on a headline that implies that the data were obtained during the pandemic.

2. Fluctuations tend to occur from year to year. Thankfully, youth suicide remains rare (although not rare enough). With small numbers, regular variations from year to year can look huge in terms of percentages, especially if one doesn’t pull back and look at longer trends over time.

3. People are reaching out for mental health services. The public health message to access support and treatment for COVID 19–related mental health struggles appears to be having an effect, but this increased demand should not necessarily be viewed as a proxy for suicidal ideation and attempts.

While the understanding that we are not actually in the midst of a surge in COVID 19–related youth suicide is reassuring, it is important not to get complacent. Much of the data remains preliminary, and, even if these numbers hold up, there is no guarantee that things will continue this way, especially if the pandemic and it restrictions continue to drag on for many more months. And of course, whether or not the pandemic is making things significantly worse, youth suicide remains an enormous public health imperative with every one being a human tragedy.

It is also quite possible that more detailed analyses will eventually reveal a more complex association between youth suicide and COVID-19, with effects of the pandemic being realized regionally or more for some groups than others. Data from before the pandemic indicated, for example, that suicide rates are increasing more rapidly among African American youth compared with white children and adolescents.⁶ With the COVID-19 pandemic itself affecting disadvantaged communities more strongly, one could readily expect variable impacts in mental health related to race or socioeconomic status. A recent article voices these concerns for indigenous youth in Montana: a state with one of the highest per capita suicide rates in the country.⁷ The article notes, however, that the rate of suicide overall in Montana in 2020 is comparable to those of previous years.

Overall, pediatricians should not be needlessly panicked that the COVID-19 pandemic has sparked a surge in youth suicide. The data at this point simply don’t support that assertion despite many headlines to the contrary. At the same time, many children and adolescents are certainly struggling with the stresses the pandemic has created and continue to need our close monitoring and support.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine. Follow him on Twitter @PediPsych. His new book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood,” launches Feb. 1, 2021.

References

1. Copeland WE et al. Impact of COVID-19 pandemic on college student mental health and wellness. J Am Acad Child Adolesc Psychiatry. 2020;60(1):134-41. doi: 10.1016/j.jaac.2020.08.466.

2. Qiu J et al. A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen Psychiatry. 2020;33:e100213. doi: 10.1136/gpsych-2020-100213.

3. Dhmara K. With teen suicides on the rise, Tucson educators struggle to prioritize mental health. Tuscon.com. Dec. 27, 2020.

4. Chafouleas, SM. America is facing a suicide epidemic: New data confirm the urgency of confronting it now. Psychology Today blog. Sept. 4, 2020.

5. Hill RM et al. Suicide ideation and attempts in a pediatric emergency department before and after COVID-19. Pediatrics. 2020. doi: 10.1542/peds.2020-029280.

6. John A et al. Trends in suicide during the covid-19 pandemic. BMJ 2020;371:m4352. doi: 10.1136/bmj.m4352.

7. Reardon S. Health officials fear COVID-19 pandemic-related suicide spike among indigenous youth. Time Magazine. December 2020.

There’s little doubt that the COVID-19 pandemic has been hard on many children and adolescents just as it has been difficult for adults. The disruption of routines, reduced contact with friends, concern over getting ill, and financial turmoil suffered by many families is exacting a toll on our mental health, as has been documented by a number of recent surveys and studies.^1,2

Quite understandably, concern about rising levels of anxiety and depression in youth prompts additional worries about suicide, the second leading cause of death in adolescents and young adults. In response, many organizations have rallied to provide additional resources to help prevent suicidal thinking and actions. Online mental health tips, support phone and text lines, and the availability of telemedicine have all been mobilized to help people cope and stay safe both physically and psychologically.

But what are the actual numbers when it comes to youth suicide during COVID-19? According to many headlines in the press, the statistics are grim and support many of distressing predictions that have been made. A December story in an Arizona newspaper, “With Teen Suicides on the Rise, Tucson Educators Struggle to Prioritize Mental Health,” described a 67% increase in teen suicides in 2020 compared with 2019 in one county.³ Another post from Psychology Today, “America is Facing a Teen Suicide Pandemic,” raised similar alarms.⁴ Concern over suicide has even been used politically to argue against restrictions that could reduce the spread of COVID-19 infections.

But despite this common perception shared by both health care professionals and the public, there actually is not evidence at this point that the COVID-19 pandemic has led to a broad spike in youth suicide deaths or attempts. A recent study published in the journal Pediatrics compared suicide screening results on youth presenting to emergency departments for any reason in 2020 to the same month in 2019.⁵ The authors found no consistent increases in reported suicidal ideation or suicide attempts with scattered elevations found in some months during 2020 compared with the previous year (including February 2020 before the pandemic really began) but not others. Internationally, newly analyzed data from 2020 with regard to suicide deaths have suggested “either no rise in suicide rates ... or a fall in the early months of the pandemic.” In my home and, admittedly small, state of Vermont, data from the Department of Health have shown 93 suicide deaths across all ages as of mid-November 2020 compared with a 5-year average of 96.

Why don’t the data match the headlines? There are a number of possibilities.

1. Suicide rates in youth were going up before the pandemic. As it takes time to verify and analyze data from large populations, many of the reports on suicide that have been published and released in 2020 summarize data from prior years. Without looking closely, a news organization can easily slap on a headline that implies that the data were obtained during the pandemic.

2. Fluctuations tend to occur from year to year. Thankfully, youth suicide remains rare (although not rare enough). With small numbers, regular variations from year to year can look huge in terms of percentages, especially if one doesn’t pull back and look at longer trends over time.

3. People are reaching out for mental health services. The public health message to access support and treatment for COVID 19–related mental health struggles appears to be having an effect, but this increased demand should not necessarily be viewed as a proxy for suicidal ideation and attempts.

While the understanding that we are not actually in the midst of a surge in COVID 19–related youth suicide is reassuring, it is important not to get complacent. Much of the data remains preliminary, and, even if these numbers hold up, there is no guarantee that things will continue this way, especially if the pandemic and it restrictions continue to drag on for many more months. And of course, whether or not the pandemic is making things significantly worse, youth suicide remains an enormous public health imperative with every one being a human tragedy.

It is also quite possible that more detailed analyses will eventually reveal a more complex association between youth suicide and COVID-19, with effects of the pandemic being realized regionally or more for some groups than others. Data from before the pandemic indicated, for example, that suicide rates are increasing more rapidly among African American youth compared with white children and adolescents.⁶ With the COVID-19 pandemic itself affecting disadvantaged communities more strongly, one could readily expect variable impacts in mental health related to race or socioeconomic status. A recent article voices these concerns for indigenous youth in Montana: a state with one of the highest per capita suicide rates in the country.⁷ The article notes, however, that the rate of suicide overall in Montana in 2020 is comparable to those of previous years.

Overall, pediatricians should not be needlessly panicked that the COVID-19 pandemic has sparked a surge in youth suicide. The data at this point simply don’t support that assertion despite many headlines to the contrary. At the same time, many children and adolescents are certainly struggling with the stresses the pandemic has created and continue to need our close monitoring and support.
 

Dr. Rettew is a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine. Follow him on Twitter @PediPsych. His new book, “Parenting Made Complicated: What Science Really Knows About the Greatest Debates of Early Childhood,” launches Feb. 1, 2021.

References

1. Copeland WE et al. Impact of COVID-19 pandemic on college student mental health and wellness. J Am Acad Child Adolesc Psychiatry. 2020;60(1):134-41. doi: 10.1016/j.jaac.2020.08.466.

2. Qiu J et al. A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen Psychiatry. 2020;33:e100213. doi: 10.1136/gpsych-2020-100213.

3. Dhmara K. With teen suicides on the rise, Tucson educators struggle to prioritize mental health. Tuscon.com. Dec. 27, 2020.

4. Chafouleas, SM. America is facing a suicide epidemic: New data confirm the urgency of confronting it now. Psychology Today blog. Sept. 4, 2020.

5. Hill RM et al. Suicide ideation and attempts in a pediatric emergency department before and after COVID-19. Pediatrics. 2020. doi: 10.1542/peds.2020-029280.

6. John A et al. Trends in suicide during the covid-19 pandemic. BMJ 2020;371:m4352. doi: 10.1136/bmj.m4352.

7. Reardon S. Health officials fear COVID-19 pandemic-related suicide spike among indigenous youth. Time Magazine. December 2020.

Black women are significantly more likely than non-Black women to develop major depression within a month of early pregnancy loss, based on data from a secondary analysis of 300 women.

Approximately 25% of women experience a pregnancy loss, and many of these women are at increased risk for psychological problems including major depression, wrote Jade M. Shorter, MD, of Stanford (Calif.) University, and colleagues.

Data from previous studies show that Black women experience higher rates of perinatal depression, compared with other racial groups, and that stress and adverse childhood experiences also are higher among Black individuals, they noted.

“Based on data showing higher rates of pregnancy loss, perinatal depression, and perceived stress in Black women, we hypothesized that the odds of having risk for major depression or high perceived stress 30 days after miscarriage treatment would be higher in Black participants when compared with non-Black participants,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers conducted a secondary analysis of 300 women aged 18 years and older with nonviable intrauterine pregnancy between 5 and 12 weeks’ gestation who were part of a larger randomized trial conducted between May 2014 and April 2017. The women were randomized to medical treatment of either mifepristone 200 mg orally plus misoprostol 800 mcg vaginally after 24 hours or the usual treatment of misoprostol 800 mcg vaginally.

Depression was assessed using the Center for Epidemiological Studies–Depression scale, Perceived Stress Scale, and Adverse Childhood Experience scale. Adverse childhood experience data were collected at baseline; stress and depression data were collected at baseline and at 30 days after treatment.

A total of 120 participants self-identified as Black and 155 self-identified as non-Black.
 

Depression risk doubles in Black women

At 30 days after treatment for early pregnancy loss, 24% of women met criteria for major depression, including 57% of Black women and 43% of non-Black women. The odds of depression were twice as high among Black women, compared with non-Black women (odds ratio 2.02), and Black women were more likely to be younger, have lower levels of education, and have public insurance, compared with non-Black women.

The association between Black race and increased risk for depression at 30 days after treatment persisted after controlling for factors including parity, baseline depression, and adverse childhood experiences, the researchers noted.

The study findings were limited by several factors, including the potential for different depression risk in those from the original study who did and did not participate in the secondary analysis and by the use of the original Adverse Childhood Experience survey, which may not reflect the range of adversity faced by different demographic groups, the researchers noted. However, the results were strengthened by the collection of 30-day outcome data in the clinical setting and by the diverse study population.

“These findings should be not be used to stigmatize Black women; instead, it is important to consider the complex systemic factors, such as structural racism, that are the root causes of disparate health outcomes,” and to support appropriate mental health resources and interventions for all women who experience early pregnancy loss, the researchers emphasized.
 

Recognize risks, reduce barriers

“Early pregnancy loss is unfortunately a common event that affects 15%-20% of pregnancies,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

However, “the mental health impact of early pregnancy loss is understudied, and as a result mental health disorders often go unnoticed and untreated,” she said.

Growing evidence shows that Black women in particular are at greater risk for chronic stressors that affect their overall health. “Black women are more likely to be exposed to trauma in their lifetime, such as physical and emotional abuse, neglect, and household instability, all of which predispose women to mental health disorders such as depression. Untreated maternal depression has an impact on future pregnancy outcomes such as increasing the risk of having a preterm delivery and/or delivering a low-birth-weight baby, outcomes where Black women are at disproportionately high risk in comparison to non-Black women,” Dr. Krishna said.

“This study found that the risk for depression after an early pregnancy loss is twice as high for Black women in comparison to non-Black women. The findings of this study further underscore the fact that Black women are at disproportionate high risk for poor maternal and pregnancy outcomes,” Dr. Krishna added.

“Structural racism is a major barrier to caring for the health of Black women. To care for the health of Black women we must overcome racial and ethnic disparities. Addressing disparities involves a multitiered approach, including identifying and addressing implicit bias in health care and improving access to health care for women of color,” she said.

“Additional research is needed in identifying at-risk women and mental health interventions that can improve the mental well-being of women after adverse pregnancy outcomes such as early pregnancy loss,” Dr. Krishna concluded.

The study was supported by the Society of Family Planning Research Fund. Lead author Dr. Shorter had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose.

SOURCE: Shorter JM et al. Obstet Gynecol. 2020 Dec 3. doi: 10.1097/AOG.0000000000004212.

Black women are significantly more likely than non-Black women to develop major depression within a month of early pregnancy loss, based on data from a secondary analysis of 300 women.

Approximately 25% of women experience a pregnancy loss, and many of these women are at increased risk for psychological problems including major depression, wrote Jade M. Shorter, MD, of Stanford (Calif.) University, and colleagues.

Data from previous studies show that Black women experience higher rates of perinatal depression, compared with other racial groups, and that stress and adverse childhood experiences also are higher among Black individuals, they noted.

“Based on data showing higher rates of pregnancy loss, perinatal depression, and perceived stress in Black women, we hypothesized that the odds of having risk for major depression or high perceived stress 30 days after miscarriage treatment would be higher in Black participants when compared with non-Black participants,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers conducted a secondary analysis of 300 women aged 18 years and older with nonviable intrauterine pregnancy between 5 and 12 weeks’ gestation who were part of a larger randomized trial conducted between May 2014 and April 2017. The women were randomized to medical treatment of either mifepristone 200 mg orally plus misoprostol 800 mcg vaginally after 24 hours or the usual treatment of misoprostol 800 mcg vaginally.

Depression was assessed using the Center for Epidemiological Studies–Depression scale, Perceived Stress Scale, and Adverse Childhood Experience scale. Adverse childhood experience data were collected at baseline; stress and depression data were collected at baseline and at 30 days after treatment.

A total of 120 participants self-identified as Black and 155 self-identified as non-Black.
 

Depression risk doubles in Black women

At 30 days after treatment for early pregnancy loss, 24% of women met criteria for major depression, including 57% of Black women and 43% of non-Black women. The odds of depression were twice as high among Black women, compared with non-Black women (odds ratio 2.02), and Black women were more likely to be younger, have lower levels of education, and have public insurance, compared with non-Black women.

The association between Black race and increased risk for depression at 30 days after treatment persisted after controlling for factors including parity, baseline depression, and adverse childhood experiences, the researchers noted.

The study findings were limited by several factors, including the potential for different depression risk in those from the original study who did and did not participate in the secondary analysis and by the use of the original Adverse Childhood Experience survey, which may not reflect the range of adversity faced by different demographic groups, the researchers noted. However, the results were strengthened by the collection of 30-day outcome data in the clinical setting and by the diverse study population.

“These findings should be not be used to stigmatize Black women; instead, it is important to consider the complex systemic factors, such as structural racism, that are the root causes of disparate health outcomes,” and to support appropriate mental health resources and interventions for all women who experience early pregnancy loss, the researchers emphasized.
 

Recognize risks, reduce barriers

“Early pregnancy loss is unfortunately a common event that affects 15%-20% of pregnancies,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

However, “the mental health impact of early pregnancy loss is understudied, and as a result mental health disorders often go unnoticed and untreated,” she said.

Growing evidence shows that Black women in particular are at greater risk for chronic stressors that affect their overall health. “Black women are more likely to be exposed to trauma in their lifetime, such as physical and emotional abuse, neglect, and household instability, all of which predispose women to mental health disorders such as depression. Untreated maternal depression has an impact on future pregnancy outcomes such as increasing the risk of having a preterm delivery and/or delivering a low-birth-weight baby, outcomes where Black women are at disproportionately high risk in comparison to non-Black women,” Dr. Krishna said.

“This study found that the risk for depression after an early pregnancy loss is twice as high for Black women in comparison to non-Black women. The findings of this study further underscore the fact that Black women are at disproportionate high risk for poor maternal and pregnancy outcomes,” Dr. Krishna added.

“Structural racism is a major barrier to caring for the health of Black women. To care for the health of Black women we must overcome racial and ethnic disparities. Addressing disparities involves a multitiered approach, including identifying and addressing implicit bias in health care and improving access to health care for women of color,” she said.

“Additional research is needed in identifying at-risk women and mental health interventions that can improve the mental well-being of women after adverse pregnancy outcomes such as early pregnancy loss,” Dr. Krishna concluded.

The study was supported by the Society of Family Planning Research Fund. Lead author Dr. Shorter had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose.

SOURCE: Shorter JM et al. Obstet Gynecol. 2020 Dec 3. doi: 10.1097/AOG.0000000000004212.

Black women are significantly more likely than non-Black women to develop major depression within a month of early pregnancy loss, based on data from a secondary analysis of 300 women.

Approximately 25% of women experience a pregnancy loss, and many of these women are at increased risk for psychological problems including major depression, wrote Jade M. Shorter, MD, of Stanford (Calif.) University, and colleagues.

Data from previous studies show that Black women experience higher rates of perinatal depression, compared with other racial groups, and that stress and adverse childhood experiences also are higher among Black individuals, they noted.

“Based on data showing higher rates of pregnancy loss, perinatal depression, and perceived stress in Black women, we hypothesized that the odds of having risk for major depression or high perceived stress 30 days after miscarriage treatment would be higher in Black participants when compared with non-Black participants,” they wrote.

In a study published in Obstetrics & Gynecology, the researchers conducted a secondary analysis of 300 women aged 18 years and older with nonviable intrauterine pregnancy between 5 and 12 weeks’ gestation who were part of a larger randomized trial conducted between May 2014 and April 2017. The women were randomized to medical treatment of either mifepristone 200 mg orally plus misoprostol 800 mcg vaginally after 24 hours or the usual treatment of misoprostol 800 mcg vaginally.

Depression was assessed using the Center for Epidemiological Studies–Depression scale, Perceived Stress Scale, and Adverse Childhood Experience scale. Adverse childhood experience data were collected at baseline; stress and depression data were collected at baseline and at 30 days after treatment.

A total of 120 participants self-identified as Black and 155 self-identified as non-Black.
 

Depression risk doubles in Black women

At 30 days after treatment for early pregnancy loss, 24% of women met criteria for major depression, including 57% of Black women and 43% of non-Black women. The odds of depression were twice as high among Black women, compared with non-Black women (odds ratio 2.02), and Black women were more likely to be younger, have lower levels of education, and have public insurance, compared with non-Black women.

The association between Black race and increased risk for depression at 30 days after treatment persisted after controlling for factors including parity, baseline depression, and adverse childhood experiences, the researchers noted.

The study findings were limited by several factors, including the potential for different depression risk in those from the original study who did and did not participate in the secondary analysis and by the use of the original Adverse Childhood Experience survey, which may not reflect the range of adversity faced by different demographic groups, the researchers noted. However, the results were strengthened by the collection of 30-day outcome data in the clinical setting and by the diverse study population.

“These findings should be not be used to stigmatize Black women; instead, it is important to consider the complex systemic factors, such as structural racism, that are the root causes of disparate health outcomes,” and to support appropriate mental health resources and interventions for all women who experience early pregnancy loss, the researchers emphasized.
 

Recognize risks, reduce barriers

“Early pregnancy loss is unfortunately a common event that affects 15%-20% of pregnancies,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

However, “the mental health impact of early pregnancy loss is understudied, and as a result mental health disorders often go unnoticed and untreated,” she said.

Growing evidence shows that Black women in particular are at greater risk for chronic stressors that affect their overall health. “Black women are more likely to be exposed to trauma in their lifetime, such as physical and emotional abuse, neglect, and household instability, all of which predispose women to mental health disorders such as depression. Untreated maternal depression has an impact on future pregnancy outcomes such as increasing the risk of having a preterm delivery and/or delivering a low-birth-weight baby, outcomes where Black women are at disproportionately high risk in comparison to non-Black women,” Dr. Krishna said.

“This study found that the risk for depression after an early pregnancy loss is twice as high for Black women in comparison to non-Black women. The findings of this study further underscore the fact that Black women are at disproportionate high risk for poor maternal and pregnancy outcomes,” Dr. Krishna added.

“Structural racism is a major barrier to caring for the health of Black women. To care for the health of Black women we must overcome racial and ethnic disparities. Addressing disparities involves a multitiered approach, including identifying and addressing implicit bias in health care and improving access to health care for women of color,” she said.

“Additional research is needed in identifying at-risk women and mental health interventions that can improve the mental well-being of women after adverse pregnancy outcomes such as early pregnancy loss,” Dr. Krishna concluded.

The study was supported by the Society of Family Planning Research Fund. Lead author Dr. Shorter had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose.

SOURCE: Shorter JM et al. Obstet Gynecol. 2020 Dec 3. doi: 10.1097/AOG.0000000000004212.

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

A simple, noninvasive EEG may help detect residual cognition in unresponsive patients who have experienced a traumatic brain injury (TBI), results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.

“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.

The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.

The study was published online Dec. 23, 2020, in Annals of Neurology.
 

Useful information at a time of ‘considerable prognostic uncertainty’

Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.

These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.

The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.

Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.

The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.

For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.

The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.

The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.

Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.

Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.

Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.

After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.

The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.

Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.

Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.

“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.

Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.

“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”

A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.

“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”

The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.

The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.

Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
 

A prognostic tool

The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.

The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”

To use it in clinical setting, “we really have to have robust measures,” she added.

She aims to conduct a collaborative study involving several institutions and more patients.

The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”

She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”

But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.

And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
 

Promising basic research

Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”

“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”

It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.

She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”

One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”

In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”

Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.

The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.

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

A simple, noninvasive EEG may help detect residual cognition in unresponsive patients who have experienced a traumatic brain injury (TBI), results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.

“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.

The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.

The study was published online Dec. 23, 2020, in Annals of Neurology.
 

Useful information at a time of ‘considerable prognostic uncertainty’

Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.

These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.

The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.

Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.

The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.

For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.

The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.

The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.

Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.

Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.

Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.

After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.

The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.

Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.

Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.

“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.

Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.

“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”

A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.

“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”

The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.

The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.

Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
 

A prognostic tool

The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.

The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”

To use it in clinical setting, “we really have to have robust measures,” she added.

She aims to conduct a collaborative study involving several institutions and more patients.

The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”

She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”

But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.

And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
 

Promising basic research

Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”

“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”

It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.

She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”

One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”

In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”

Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.

The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.

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

A simple, noninvasive EEG may help detect residual cognition in unresponsive patients who have experienced a traumatic brain injury (TBI), results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.

“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.

The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.

The study was published online Dec. 23, 2020, in Annals of Neurology.
 

Useful information at a time of ‘considerable prognostic uncertainty’

Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.

These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.

The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.

Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.

The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.

For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.

The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.

The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.

Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.

Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.

Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.

After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.

The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.

Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.

Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.

“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.

Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.

“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”

A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.

“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”

The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.

The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.

Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
 

A prognostic tool

The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.

The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”

To use it in clinical setting, “we really have to have robust measures,” she added.

She aims to conduct a collaborative study involving several institutions and more patients.

The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”

She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”

But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.

And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
 

Promising basic research

Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”

“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”

It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.

She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”

One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”

In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”

Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.

The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.

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

Cloth masks should not be considered equivalent to medical masks for the prevention of COVID-19 in clinical settings, according to an evidence review published Jan. 11 in Annals of Family Medicine.

Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.

And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.

“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.

The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
 

Filtration and fit

“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.

One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.

Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.

Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.

Generally consistent guidance

Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.

“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”

Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.

In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.

“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”

In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
 

Not considered PPE

According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”

Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.

“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.

When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.

In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
 

Limited data for comparisons

A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.

In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.

The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.

[email protected]

SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.

Cloth masks should not be considered equivalent to medical masks for the prevention of COVID-19 in clinical settings, according to an evidence review published Jan. 11 in Annals of Family Medicine.

Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.

And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.

“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.

The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
 

Filtration and fit

“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.

One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.

Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.

Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.

Generally consistent guidance

Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.

“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”

Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.

In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.

“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”

In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
 

Not considered PPE

According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”

Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.

“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.

When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.

In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
 

Limited data for comparisons

A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.

In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.

The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.

[email protected]

SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.

Cloth masks should not be considered equivalent to medical masks for the prevention of COVID-19 in clinical settings, according to an evidence review published Jan. 11 in Annals of Family Medicine.

Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.

And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.

“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.

The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
 

Filtration and fit

“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.

One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.

Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.

Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.

Generally consistent guidance

Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.

“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”

Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.

In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.

“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”

In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
 

Not considered PPE

According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”

Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.

“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.

When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.

In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
 

Limited data for comparisons

A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.

In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.

The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.

[email protected]

SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The real strength of the 4T score for heparin-induced thrombocytopenia (HIT) is its negative predictive value, according to hematologist Adam Cuker, MD, of the department of medicine at the University of Pennsylvania, Philadelphia.

The score assigns patients points based on degree of thrombocytopenia, timing of platelet count fall in relation to heparin exposure, presence of thrombosis and other sequelae, and the likelihood of other causes of thrombocytopenia.

A low score – 3 points or less – has a negative predictive value of 99.8%, “so HIT is basically ruled out; you do not need to order lab testing for HIT or manage the patient empirically for HIT,” and should look for other causes of thrombocytopenia, said Dr. Cuker, lead author of the American Society of Hematology’s most recent HIT guidelines.

Intermediate scores of 4 or 5 points, and high scores of 6-8 points, are a different story. The positive predictive value of an intermediate score is only 14%, and of a high score, 64%, so although they don’t confirm the diagnosis, “you have to take the possibility of HIT seriously.” Discontinue heparin, start a nonheparin anticoagulant, and order a HIT immunoassay. If it’s positive, order a functional assay to confirm the diagnosis, he said.

Suspicion of HIT “is perhaps the most common consult that we get on the hematology service. These are tough consults because it is a high-stakes decision.” There is about a 6% risk of thromboembolism, amputation, and death for every day treatment is delayed. “On the other hand, the nonheparin anticoagulants are expensive, and they carry about a 1% daily risk of major bleeding,” Dr. Cuker explained during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

ELISA immunoassay detects antiplatelet factor 4 heparin antibodies but doesn’t tell whether or not they are able to activate platelets and cause HIT. Functional tests such as the serotonin-release assay detect only those antibodies able to do so, but the assays are difficult to perform, and often require samples to be sent out to a reference lab.

ASH did not specify a particular nonheparin anticoagulant in its 2018 guidelines because “the best choice for your patient” depends on which drugs you have available, your familiarity with them, and patient factors, Dr. Cuker said at the conference sponsored by MedscapeLive.

It makes sense, for instance, to use a short-acting agent such as argatroban or bivalirudin in patients who are critically ill, at high risk of bleeding, or likely to need an urgent unplanned procedure. Fondaparinux or direct oral anticoagulants (DOACs) make sense if patients are clinically stable with good organ function and no more than average bleeding risk, because they are easier to administer and facilitate transition to the outpatient setting.

DOACs are newcomers to ASH’s guidelines. Just 81 patients had been reported in the literature when they were being drafted, but only 2 patients had recurrence or progression of thromboembolic events, and there were no major bleeds. The results compared favorably with other options.

The studies were subject to selection and reporting biases, “but, nonetheless, the panel felt the results were positive enough that DOACs ought to be listed as an option,” Dr. Cuker said.

The guidelines note that parenteral options may be the best choice for life- or limb-threatening thrombosis “because few such patients have been treated with a DOAC.” Anticoagulation must continue until platelet counts recover.

Dr. Cuker is a consultant for Synergy and has institutional research support from Alexion, Bayer, Sanofi, and other companies. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.

The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.

Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.

The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.

“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”

Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.

Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.

If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.

“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.

“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.

One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.

“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”

Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.

To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.

“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”

Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.

“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.

The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.

“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”

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

The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.

The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.

Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.

The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.

“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”

Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.

Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.

If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.

“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.

“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.

One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.

“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”

Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.

To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.

“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”

Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.

“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.

The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.

“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”

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

The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.

The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.

Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.

The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.

“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”

Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.

Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.

If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.

“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.

“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.

One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.

“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”

Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.

To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.

“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”

Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.

“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.

The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.

“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”

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

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.