Pulmonology

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Pregnant women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies if they have close monitoring before, during, and after pregnancy with a multidisciplinary team of physicians, new research suggests.

Senior author Megan Clowse, MD, MPH, associate professor of medicine in the division of rheumatology at Duke University, Durham, N.C., explained during a press conference at the virtual annual meeting of the American College of Rheumatology that women with ILD are often advised by obstetricians or rheumatologists to avoid conception or terminate their pregnancies, though evidence for that has been based on small studies of 9-15 patients that have had mixed results.

“Many of these pregnancies were delivered 20-30 years ago, definitely with different rheumatic and obstetric care than we can provide now,” she said. “It’s really time to rethink our approach to interstitial lung disease and pregnancy.”

This study showed that while adverse pregnancy outcomes are common in these women, overall maternal morbidity and mortality are low.

ILD may be a secondary disease in people who have scleroderma, lupus, and sarcoidosis.

Largest study to date

This Pfizer-sponsored retrospective study of 67 pregnant women is the largest to date, and it analyzed 94 pregnancies (including five sets of twins).

Sarah Rae Easter, MD, maternal-fetal medicine doctor in the department of obstetrics and gynecology at Brigham and Women’s Hospital, Boston, called the work “exciting” as the researchers were able to look back at a large number of cases for a rare condition for more than 20 years.

“Their data provides much-needed evidence to provide some reassurance for women affected by this type of pulmonary disease regarding the relative safety of pregnancy,” she said in an interview.
 

Study spanned 23 years

The researchers reviewed pregnancy records in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019.

They classified the severity of ILD based on two standard breathing tests – forced vital capacity and diffusion capacity for carbon monoxide.

Overall, 69% of the women were diagnosed with sarcoidosis and the remaining 31% had a connective tissue disease associated with ILD (CTD-ILD). Of those measured for ILD severity, 11% were severe, 25% were moderate, 50% were mild, and 14% were normal. Their average maternal age was 32.1 and 83% were Black.

While 70% of the pregnancies resulted in live births, 9% were terminated. The remainder resulted in miscarriage or stillbirth.

Researchers reported a 15% rate of preeclampsia, a 34% rate of the composite measure PROMISSE-Adverse Pregnancy Outcome (APO), and a 15% rate of PROMISSE-APO SEVERE. Patients with severe disease had the highest rates of PROMISSE-APO (P = .03 across groups).

(PROMISSE stands for the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study.)

None of the women died

Dr. Clowse said it was a pleasant surprise to find that none of the women died, though patients with severe ILD had more adverse outcomes. Only 2.1% were treated in an intensive care unit during or soon after delivery. In 4.2%, ILD patients had significant shortness of breath due to fluid volume overload around the time of delivery.

For the women who had normal-to-moderate lung disease, Dr. Clowse said, “they really had remarkably good outcomes, really pretty comparable to the general population. About 15% delivered preterm and about 20% suffered a pregnancy loss.”

Dr. Easter, who was not involved with the study, noted the large number of Black women in the cohort.

“Focusing in on improving outcomes for Black and Brown women related to pregnancy in our country is a much-needed undertaking,” Dr. Easter said.

Being able to quote percentages from this research, based on a good-sized study “at least gives people a benchmark about what kind of risk they are willing to assume for themselves,” she said.

For providers, being able to place this rare disease within the spectrum of other diseases where there is more data is also very helpful, she said.

Dr. Clowse said in an interview that the preponderance of Black women in the study was a surprise but may be explained by two factors: Sarcoidosis is seen more frequently in Black women and in the study area in North Carolina there is a large population of Black women.

“Also, our patients with more severe lupus, the ones who are more likely to have interstitial lung disease, are often Black and that’s likely contributing as well,” she said.
 

Multidisciplinary teams advised

Dr. Clowse emphasized that women with ILD need multidisciplinary teams in pregnancy and should be managed at tertiary care centers where there is a full complement of obstetric and internal medicine experts.

“We do recommend evaluating the severity of their lungs and their heart disease around the time of pregnancy and during pregnancy if they have shortness of breath,” she said.

“We currently recommend that these patients with moderate or severe disease stay in the hospital for up to a week, just for monitoring,” she said.

Dr. Easter said having that kind of access to a large academic healthcare center should be an important part of the decision-making.

Patients need to think about whether they would have access to care similar to what the researchers are describing when they are making the decision to pursue or continue pregnancy, she said.

The study was sponsored by Pfizer Inc. Dr. Clowse reported relationships with UCB, GlaxoSmithKline, AstraZeneca, and Pfizer. Dr. Easter has disclosed no relevant financial relationships.

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

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

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

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

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

For reasons unknown, about one in six people who recovered from COVID-19 subsequently retested positive at least 2 weeks later, researchers reported in a study in Italy.

Sore throat and rhinitis were the only symptoms associated with a positive result. “Patients who continued to have respiratory symptoms, especially, were more likely to have a new positive test result,” lead author Francesco Landi, MD, PhD, said in an interview.

“This suggests the persistence of respiratory symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19,” he said.

“The study results are interesting,” Akiko Iwasaki, PhD, an immunobiologist at Yale University and the Howard Hughes Medical Institute, both in New Haven, Conn.,, said in an interview. “There are other reports of RNA detection postdischarge, but this study ... found that only two symptoms out of many – sore throat and rhinitis – were higher in those with PCR [polymerase chain reaction]-positive status.”

The study was published online Sept. 18 in the American Journal of Preventive Medicine.

The findings could carry important implications for people who continue to be symptomatic. “It is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab,” said Dr. Landi, associate professor of internal medicine at Catholic University of the Sacred Heart in Rome.

“One of most interesting findings is that persistent symptoms do not correlate with PCR positivity, suggesting that symptoms are in many cases not due to ongoing viral replication,” Jonathan Karn, PhD, professor and chair of the department of molecular biology and microbiology at Case Western Reserve University, Cleveland, said in an interview.

“The key technical problem, which they have discussed, is that a viral RNA signal in the PCR assay does not necessarily mean that infectious virus is present,” Dr. Karn said. He added that new comprehensive viral RNA analyses would be needed to answer this question.
 

Official COVID-19 recovery

To identify risk factors and COVID-19 survivors more likely to retest positive, Dr. Landi and members of the Gemelli Against COVID-19 Post-Acute Care Study Group evaluated 131 people after hospital discharge.

All participants met World Health Organization criteria for release from isolation, including two negative test results at least 24 hours apart, and were studied between April 21 and May 21. Mean age was 56 and 39% were women. Only a slightly higher mean body mass index of 27.6 kg/m² in the positive group versus 25.9 in the negative group, was significant.

Although 51% of survivors reported fatigue, 44% had dyspnea, and 17% were coughing, the rates did not differ significantly between groups. In contrast, 18% of positive survivors and 4% of negative survivors had a sore throat (P = .04), and 27% versus 12%, respectively, reported rhinitis (P = .05).

People returned for follow-up visits a mean 17 days after the second negative swab test.
 

Asymptomatic COVID-19 carriers

“These findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus,” the researchers noted in the paper. “Even in the absence of specific guidelines, the 22 patients who tested positive for COVID-19 again were suggested to quarantine for a second time.”

No family member or close contact of the positive survivors reported SARS-CoV-2 infection. All patients continued to wear masks and observe social distancing recommendations, which makes it “very difficult to affirm whether these patients were really contagious,” the researchers noted.
 

Next steps

Evaluating all COVID-19 survivors to identify any who retest positive “will be a crucial contribution to a better understanding of both the natural history of COVID-19 as well as the public health implications of viral shedding,” the authors wrote.

One study limitation is that the reverse transcriptase–PCR test reveals genetic sequences specific to COVID-19. “It is important to underline that this is not a viral culture and cannot determine whether the virus is viable and transmissible,” the researchers noted.

“In this respect, we are trying to better understand if the persistence of long-time positive [reverse transcriptase]–PCR test for COVID-19 is really correlated to a potential contagiousness,” they added.

Dr. Landi and colleagues said their findings should be considered preliminary, and larger data samples are warranted to validate the results.

Dr. Landi and Dr. Karn disclosed no relevant financial relationships. Dr. Iwasaki disclosed a research grant from Condair, a 5% or greater equity interest in RIGImmune, and income of $250 or more from PureTec.

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

A new poll of emergency physicians on the front lines of the COVID-19 pandemic shows many are fearful of seeking mental health care for fear of stigma and the potential career impact.

wutwhanfoto/Getty Images

The results of the nationally representative poll, conducted Oct. 7-13 by the American College of Emergency Physicians, showed almost half (45%) of 862 emergency physician respondents reported being uncomfortable seeking available psychiatric care. The poll had a margin of error of plus or minus 3 percentage points.

The findings provide new insight into both the challenges of serving in emergency medicine during the pandemic and the persistent barriers to mental health care in terms of stigma and concerns about potential career setbacks.

In the poll, 42% of respondents said they have been feeling much more stress since the start of COVID-19, with another 45% report they were feeling somewhat more stressed.

When asked about causes of stress related directly to COVID-19, 83% cited concerns about family and friends contracting COVID-19. Also factoring into emergency physicians’ stress and burnout were concerns about their own safety (80%) and lack of personal protective equipment or other needed resources (60%).

In the poll, 29% of respondents reported having excellent access to mental health treatment and 42% reported having good access. Despite this, 30% of respondents still reported feeling there was a lot of stigma in their workplace about seeking mental health treatment, with another 43% reporting they felt there was some stigma.

Poll results also showed that 24% of respondents were very concerned about what might happen with their employment if they were to seek mental health treatment, with another 33% saying they were somewhat concerned.

In recent years there have been efforts to break down cultural roadblocks in medicine that deter many physicians from seeking mental health treatment, but more needs to be done, said Mark Rosenberg, DO, MBA, who was elected president of ACEP at last weekend’s annual meeting, ACEP20.

“The pandemic emphatically underscores our need to change the status quo when it comes to physicians’ mental health,” Dr. Rosenberg said.

As previously reported by Medscape Medical News, current efforts to remove such barriers include initiatives to limit inquiries into clinicians’ past or present mental health treatment.

In May, the influential Joint Commission issued a statement urging organizations to refrain from asking about any history of mental health conditions or treatment. The Joint Commission said it supports recommendations already made by the Federation of State Medical Boards and the American Medical Association to limit inquiries on licensing applications to conditions that currently impair a clinician’s ability to perform their job.

Also supporting these efforts is the Dr. Lorna Breen Heroes’ Foundation, created in honor of an emergency physician who died by suicide in April amid the pandemic.

Lorna Breen, MD, had been working intensely in the response to the pandemic. During one shift, she covered two EDs in Manhattan at locations 5 miles apart, according to a backgrounder on the foundation’s web site.

At an ACEP press conference this week, Dr. Breen’s brother-in-law, J. Corey Feist, JD, MBA, cofounder of the foundation, noted that some states’ licensing applications for physicians include questions that fall outside of the boundaries of the Americans With Disabilities Act. He cited an analysis of state medical boards’ initial licensing questions published in 2018 in the Journal of the American Academy of Psychiatry and the Law.

In many cases, states have posed questions that extend beyond an assessment of a physician’s current ability to care for patients, creating a needless hurdle to seeking care, wrote the paper’s lead author, Carol North, MD, of the University of Texas Southwestern Medical Center, Dallas.

“Over the years, many medical licensure boards have asked applicants intrusive questions about whether they have any psychiatric history. This has created a major problem for applicants, and unfortunately this has discouraged many of those who need psychiatric treatment from seeking it because of fear of the questions,” Dr. North and colleagues noted. They cited Ohio as an example of a state that had overhauled its approach to questioning to bring it in compliance with the ADA.

Ohio previously required applicants to answer lengthy questions about their mental health, including:

• Within the last 10 years, have you been diagnosed with or have you been treated for bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Have you, since attaining the age of eighteen or within the last 10 years, whichever period is shorter, been admitted to a hospital or other facility for the treatment of bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Do you have, or have you been diagnosed as having, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?

In the new version, the single question reads: “In the past 5 years, have you been diagnosed as having, or been hospitalized for, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?”

Other states such as New York pose no mental health questions on applications for licensure.

Still, even when states have nondiscriminatory laws, physicians may not be aware of them, said Mr. Feist at an ACEP press conference. In addition to his work with the foundation, Mr. Feist is the CEO of the University of Virginia Physicians Group.

He said his sister-in-law Dr. Breen may have worried without cause about potential consequences of seeking psychiatric treatment during the pandemic. In addition, physicians in need of psychiatric care may worry about encountering hitches with medical organizations and insurers.

“This stigma and this fear of professional action on your license or your credentialing or privileging is pervasive throughout the industry,” he said.

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

A new poll of emergency physicians on the front lines of the COVID-19 pandemic shows many are fearful of seeking mental health care for fear of stigma and the potential career impact.

wutwhanfoto/Getty Images

The results of the nationally representative poll, conducted Oct. 7-13 by the American College of Emergency Physicians, showed almost half (45%) of 862 emergency physician respondents reported being uncomfortable seeking available psychiatric care. The poll had a margin of error of plus or minus 3 percentage points.

The findings provide new insight into both the challenges of serving in emergency medicine during the pandemic and the persistent barriers to mental health care in terms of stigma and concerns about potential career setbacks.

In the poll, 42% of respondents said they have been feeling much more stress since the start of COVID-19, with another 45% report they were feeling somewhat more stressed.

When asked about causes of stress related directly to COVID-19, 83% cited concerns about family and friends contracting COVID-19. Also factoring into emergency physicians’ stress and burnout were concerns about their own safety (80%) and lack of personal protective equipment or other needed resources (60%).

In the poll, 29% of respondents reported having excellent access to mental health treatment and 42% reported having good access. Despite this, 30% of respondents still reported feeling there was a lot of stigma in their workplace about seeking mental health treatment, with another 43% reporting they felt there was some stigma.

Poll results also showed that 24% of respondents were very concerned about what might happen with their employment if they were to seek mental health treatment, with another 33% saying they were somewhat concerned.

In recent years there have been efforts to break down cultural roadblocks in medicine that deter many physicians from seeking mental health treatment, but more needs to be done, said Mark Rosenberg, DO, MBA, who was elected president of ACEP at last weekend’s annual meeting, ACEP20.

“The pandemic emphatically underscores our need to change the status quo when it comes to physicians’ mental health,” Dr. Rosenberg said.

As previously reported by Medscape Medical News, current efforts to remove such barriers include initiatives to limit inquiries into clinicians’ past or present mental health treatment.

In May, the influential Joint Commission issued a statement urging organizations to refrain from asking about any history of mental health conditions or treatment. The Joint Commission said it supports recommendations already made by the Federation of State Medical Boards and the American Medical Association to limit inquiries on licensing applications to conditions that currently impair a clinician’s ability to perform their job.

Also supporting these efforts is the Dr. Lorna Breen Heroes’ Foundation, created in honor of an emergency physician who died by suicide in April amid the pandemic.

Lorna Breen, MD, had been working intensely in the response to the pandemic. During one shift, she covered two EDs in Manhattan at locations 5 miles apart, according to a backgrounder on the foundation’s web site.

At an ACEP press conference this week, Dr. Breen’s brother-in-law, J. Corey Feist, JD, MBA, cofounder of the foundation, noted that some states’ licensing applications for physicians include questions that fall outside of the boundaries of the Americans With Disabilities Act. He cited an analysis of state medical boards’ initial licensing questions published in 2018 in the Journal of the American Academy of Psychiatry and the Law.

In many cases, states have posed questions that extend beyond an assessment of a physician’s current ability to care for patients, creating a needless hurdle to seeking care, wrote the paper’s lead author, Carol North, MD, of the University of Texas Southwestern Medical Center, Dallas.

“Over the years, many medical licensure boards have asked applicants intrusive questions about whether they have any psychiatric history. This has created a major problem for applicants, and unfortunately this has discouraged many of those who need psychiatric treatment from seeking it because of fear of the questions,” Dr. North and colleagues noted. They cited Ohio as an example of a state that had overhauled its approach to questioning to bring it in compliance with the ADA.

Ohio previously required applicants to answer lengthy questions about their mental health, including:

• Within the last 10 years, have you been diagnosed with or have you been treated for bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Have you, since attaining the age of eighteen or within the last 10 years, whichever period is shorter, been admitted to a hospital or other facility for the treatment of bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Do you have, or have you been diagnosed as having, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?

In the new version, the single question reads: “In the past 5 years, have you been diagnosed as having, or been hospitalized for, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?”

Other states such as New York pose no mental health questions on applications for licensure.

Still, even when states have nondiscriminatory laws, physicians may not be aware of them, said Mr. Feist at an ACEP press conference. In addition to his work with the foundation, Mr. Feist is the CEO of the University of Virginia Physicians Group.

He said his sister-in-law Dr. Breen may have worried without cause about potential consequences of seeking psychiatric treatment during the pandemic. In addition, physicians in need of psychiatric care may worry about encountering hitches with medical organizations and insurers.

“This stigma and this fear of professional action on your license or your credentialing or privileging is pervasive throughout the industry,” he said.

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

A new poll of emergency physicians on the front lines of the COVID-19 pandemic shows many are fearful of seeking mental health care for fear of stigma and the potential career impact.

wutwhanfoto/Getty Images

The results of the nationally representative poll, conducted Oct. 7-13 by the American College of Emergency Physicians, showed almost half (45%) of 862 emergency physician respondents reported being uncomfortable seeking available psychiatric care. The poll had a margin of error of plus or minus 3 percentage points.

The findings provide new insight into both the challenges of serving in emergency medicine during the pandemic and the persistent barriers to mental health care in terms of stigma and concerns about potential career setbacks.

In the poll, 42% of respondents said they have been feeling much more stress since the start of COVID-19, with another 45% report they were feeling somewhat more stressed.

When asked about causes of stress related directly to COVID-19, 83% cited concerns about family and friends contracting COVID-19. Also factoring into emergency physicians’ stress and burnout were concerns about their own safety (80%) and lack of personal protective equipment or other needed resources (60%).

In the poll, 29% of respondents reported having excellent access to mental health treatment and 42% reported having good access. Despite this, 30% of respondents still reported feeling there was a lot of stigma in their workplace about seeking mental health treatment, with another 43% reporting they felt there was some stigma.

Poll results also showed that 24% of respondents were very concerned about what might happen with their employment if they were to seek mental health treatment, with another 33% saying they were somewhat concerned.

In recent years there have been efforts to break down cultural roadblocks in medicine that deter many physicians from seeking mental health treatment, but more needs to be done, said Mark Rosenberg, DO, MBA, who was elected president of ACEP at last weekend’s annual meeting, ACEP20.

“The pandemic emphatically underscores our need to change the status quo when it comes to physicians’ mental health,” Dr. Rosenberg said.

As previously reported by Medscape Medical News, current efforts to remove such barriers include initiatives to limit inquiries into clinicians’ past or present mental health treatment.

In May, the influential Joint Commission issued a statement urging organizations to refrain from asking about any history of mental health conditions or treatment. The Joint Commission said it supports recommendations already made by the Federation of State Medical Boards and the American Medical Association to limit inquiries on licensing applications to conditions that currently impair a clinician’s ability to perform their job.

Also supporting these efforts is the Dr. Lorna Breen Heroes’ Foundation, created in honor of an emergency physician who died by suicide in April amid the pandemic.

Lorna Breen, MD, had been working intensely in the response to the pandemic. During one shift, she covered two EDs in Manhattan at locations 5 miles apart, according to a backgrounder on the foundation’s web site.

At an ACEP press conference this week, Dr. Breen’s brother-in-law, J. Corey Feist, JD, MBA, cofounder of the foundation, noted that some states’ licensing applications for physicians include questions that fall outside of the boundaries of the Americans With Disabilities Act. He cited an analysis of state medical boards’ initial licensing questions published in 2018 in the Journal of the American Academy of Psychiatry and the Law.

In many cases, states have posed questions that extend beyond an assessment of a physician’s current ability to care for patients, creating a needless hurdle to seeking care, wrote the paper’s lead author, Carol North, MD, of the University of Texas Southwestern Medical Center, Dallas.

“Over the years, many medical licensure boards have asked applicants intrusive questions about whether they have any psychiatric history. This has created a major problem for applicants, and unfortunately this has discouraged many of those who need psychiatric treatment from seeking it because of fear of the questions,” Dr. North and colleagues noted. They cited Ohio as an example of a state that had overhauled its approach to questioning to bring it in compliance with the ADA.

Ohio previously required applicants to answer lengthy questions about their mental health, including:

• Within the last 10 years, have you been diagnosed with or have you been treated for bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Have you, since attaining the age of eighteen or within the last 10 years, whichever period is shorter, been admitted to a hospital or other facility for the treatment of bipolar disorder, schizophrenia, paranoia, or any other psychotic disorder?
• Do you have, or have you been diagnosed as having, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?

In the new version, the single question reads: “In the past 5 years, have you been diagnosed as having, or been hospitalized for, a medical condition which in any way impairs or limits your ability to practice medicine with reasonable skill and safety?”

Other states such as New York pose no mental health questions on applications for licensure.

Still, even when states have nondiscriminatory laws, physicians may not be aware of them, said Mr. Feist at an ACEP press conference. In addition to his work with the foundation, Mr. Feist is the CEO of the University of Virginia Physicians Group.

He said his sister-in-law Dr. Breen may have worried without cause about potential consequences of seeking psychiatric treatment during the pandemic. In addition, physicians in need of psychiatric care may worry about encountering hitches with medical organizations and insurers.

“This stigma and this fear of professional action on your license or your credentialing or privileging is pervasive throughout the industry,” he said.

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

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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