MDedge Neurology

The meteoric rise in the number of test-positive and clinical cases of COVID-19 because of infection with the SARS coronavirus (SARS-CoV-2) in states and cities across the United States has added urgency to the efforts to develop protocols for hospital triage, admission, labor and delivery management, and other aspects of obstetrical care.

Emerging data suggest that, while SARS-CoV-2 is less lethal overall than the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) proved to be, it is significantly more contagious. Although a severe disease, the limited worldwide data so far available (as of early May) do not indicate that pregnant women are at greater risk of severe disease, compared with the general population. However, there remains a critical need for data on maternal and perinatal outcomes in women infected with SARS-CoV-2.

Multiple physiological changes in pregnancy, from reduced cell-based immune competence to changes in respiratory tract and pulmonary function – e.g., edema of the respiratory tract, increases in secretions and oxygen consumption, elevation of the diaphragm, and decrease in functional residual capacity – have historically contributed to worse obstetric outcomes in pregnant women who have had viral pneumonias. Furthermore, limited published experience with COVID-19 in China suggests worse perinatal outcomes in some affected pregnancies, including prematurity and perinatal death.

With evolution of the pandemic and accumulation of experience, it is expected that data-driven guidelines on assessment and management of infected pregnant women will contribute to improved maternal and perinatal outcomes. What is clear now, however, is that, without protecting the health of obstetricians and other health care workers, urgently needed gains in patient outcomes will not be realized.

Here are my recommendations, based on a currently limited body of literature on COVID-19 and other communicable viral respiratory disorders, as well my experience in the greater Detroit area, a COVID-19 hot spot.
 

Preparing for hospital evaluation and admission

The obstetric triage or labor and delivery (L&D) unit should be notified prior to the arrival of a patient suspected of or known to be infected with the virus. This will minimize staff exposure and allow sufficient time to prepare appropriate accommodations, equipment, and supplies for the patient’s care. Hospital infection control should be promptly notified by L&D of the expected arrival of such a patient. Placement ideally should be in a negative-pressure room, which allows outside air to flow into the room but prevents contaminated air from escaping. In the absence of a negative-pressure room, an infection isolation area should be utilized.

The patient and one accompanying support individual should wear either medical-grade masks brought from home or supplied upon entry to the hospital or homemade masks or bandanas. This will reduce the risk of viral transmission to hospital workers and other individuals encountered in the hospital prior to arriving in L&D. An ideal setup is to have separate entry areas, access corridors, and elevators for patients known or suspected to have COVID-19 infection. The patient and visitor should be expeditiously escorted to the prepared area for evaluation. Patients who are not known or suspected to be infected ideally should be tested.
 

Screening of patients & support individuals

Proper screening of patients and support individuals is critical to protecting both patients and staff in the L&D unit. This should include an expanded questionnaire that asks about disturbances of smell and taste and GI symptoms like loss of appetite – not only the more commonly queried symptoms of fever, shortness of breath, coughing, and exposure to someone who may have been ill.

Recent studies regarding presenting symptoms cast significant doubt, in fact, on the validity of patients with “asymptomatic COVID-19.” Over 15% of patients with confirmed infection in one published case series had solely GI symptoms and almost all had some digestive symptoms, for example, and almost 90% in another study had absent or reduced sense of smell and/or taste.^1,2 In fact, the use of the term “paucisymptomatic” rather than “asymptomatic” may be most appropriate.

Support individuals also should undergo temperature screening, ideally with laser noncontact thermometers on entry to the hospital or triage.
 

Visitor policy

The number of visitors/support individuals should be kept to a minimum to reduce transmission risk. The actual number will be determined by hospital or state policy, but up to one visitor in the labor room appears reasonable. Very strong individual justification should be required to exceed this threshold! The visitor should not only be screened for an expanded list of symptoms, but they also should be queried for underlying illnesses (e.g., diabetes, cardiovascular disease, significant lung disease, undergoing cancer therapy) as well as for age over 65 years, each of which increase the chances of severe COVID-19 disease should infection occur. The visitor should be informed of such risks and, especially when accompanying a patient with known or suspected COVID-19, provided the option of voluntarily revoking their visitor status. A visitor with known or suspected COVID-19 infection based on testing or screening should not be allowed into the L&D unit.

In addition, institutions may be considered to have obligations to the visitor/support person beyond screening. These include instructions in proper mask usage, hand washing, and limiting the touching of surfaces to lower infection risk.

“Visitor relays” where one visitor replaces another should be strongly discouraged. Visitors should similarly not be allowed to wander around the hospital (to use phones, for instance); transiting back and forth to obtain food and coffee should be kept to a strict minimum. For visitors accompanying COVID-19–-infected women, “visitor’s plates” provided by the hospital at reasonable cost is a much-preferred arrangement for obtaining meals during the course of the hospital stay. In addition, visitors should be sent out of the room during the performance of aerosolizing procedures.
 

Labor and delivery management

The successful management of patients with COVID-19 requires a rigorous infection control protocol informed by guidelines from national entities, such as the Centers for Disease Control and Prevention, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists, and by state health departments when available.

Strict limits on the number of obstetricians and other health care workers (HCWs) entering the patient’s room should be enforced and documented to minimize risk to the HCWs attending to patients who have a positive diagnosis or who are under investigation. Only in cases of demonstrable clinical benefit should repeat visits by the same or additional HCWs be permitted. Conventional and electronic tablets present an excellent opportunity for patient follow-up visits without room entry. In our institution, this has been successfully piloted in nonpregnant patients. Obstetricians and others caring for obstetrical patients – especially those who are infected or under investigation for infection – should always wear a properly fitted N95 mask.

Because patients with COVID-19 may have or go on to develop a constellation of organ abnormalities (e.g., cardiovascular, renal, pulmonary), it is vital that a standardized panel of baseline laboratory studies be developed for pregnant patients. This will minimize the need for repeated blood draws and other testing which may increase HCW exposure.

A negative screen based on nonreport of symptoms, lack of temperature elevation, and reported nonexposure to individuals with COVID-19 symptoms still has limitations in terms of disease detection. A recent report from a tertiary care hospital in New York City found that close to one-third of pregnant patients with confirmed COVID-19 admitted over a 2-week period had no viral symptoms or instructive history on initial admission.³ This is consistent with our clinical experience. Most importantly, therefore, routine quantitative reverse transcription polymerase chain reaction testing should be performed on all patients admitted to the L&D unit.

Given the reported variability in the accuracy of polymerase chain reaction testing induced by variable effectiveness of sampling techniques, stage of infection, and inherent test accuracy issues, symptomatic patients with a negative test should first obtain clearance from infectious disease specialists before isolation precautions are discontinued. Repeat testing in 24 hours, including testing of multiple sites, may subsequently yield a positive result in persistently symptomatic patients.
 

Intrapartum management

As much as possible, standard obstetric indications should guide the timing and route of delivery. In the case of a COVID-19–positive patient or a patient under investigation, nonobstetric factors may bear heavily on decision making, and management flexibility is of great value. For example, in cases of severe or critical disease status, evidence suggests that early delivery regardless of gestational age can improve maternal oxygenation; this supports the liberal use of C-sections in these circumstances. In addition, shortening labor length as well as duration of hospitalization may be expected to reduce the risk of transmission to HCWs, other staff, and other patients.

High rates of cesarean delivery unsurprisingly have been reported thus far: One review of 108 case reports and series of test-positive COVID-19 pregnancies found a 92% C-section rate, and another review and meta-analysis of studies of SARS, MERS, and COVID-19 during pregnancy similarly found that the majority of patients – 84% across all coronavirus infections and 91% in COVID-19 pregnancies – were delivered by C-section.4,5 Given these high rates of cesarean deliveries, the early placement of neuraxial anesthesia while the patient is stable appears to be prudent and obviates the need for intubation, the latter of which is associated with increased aerosol generation and increased virus transmission risk.

Strict protocols for the optimal protection of staff should be observed, including proper personal protective equipment (PPE) protection. Protocols have been detailed in various guidelines and publications; they include the wearing of shoe covers, gowns, N95 masks, goggles, face shields, and two layers of gloves.

For institutions that currently do not offer routine COVID-19 testing to pregnant patients – especially those in areas of outbreaks – N95 masks and eye protection should still be provided to all HCWs involved in the intrapartum management of untested asymptomatic patients, particularly those in the active phase of labor. This protection is justified given the limitations of symptom- and history-based screening and the not-uncommon experience of the patient with a negative screen who subsequently develops the clinical syndrome.

Obstetric management of labor requires close patient contact that potentially elevates the risk of contamination and infection. During the active stage of labor, patient shouting, rapid mouth breathing, and other behaviors inherent to labor all increase the risk of aerosolization of oronasal secretions. In addition, nasal-prong oxygen administration is believed to independently increase the risk of aerosolization of secretions. The casual practice of nasal oxygen application should thus be discontinued and, where felt to be absolutely necessary, a mask should be worn on top of the prongs.

Regarding operative delivery, each participating obstetric surgeon should observe guidelines and recommendations of governing national organizations and professional groups – including the American College of Surgeons – regarding the safe conduct of operations on patients with COVID-19. Written guidelines should be tailored as needed to the performance of C-sections and readily available in L&D. Drills and simulations are generally valuable, and expertise and support should always be available in the labor room to assist with donning and doffing of PPE.
 

Postpartum care

Expeditious separation of the COVID-19–positive mother from her infant is recommended, including avoidance of delayed cord clamping because of insufficient evidence of benefit to the infant. Insufficient evidence exists to support vertical transmission, but the possibility of maternal-infant transmission is clinically accepted based on small case reports of infection in a neonate at 30 hours of life and in infants of mothers with suspected or confirmed COVID-19.6,7 Accordingly, it is recommended that the benefit of early infant separation should be discussed with the mother. If approved, the infant should be kept in a separate isolation area and observed.

There is no evidence of breast milk transmission of the virus. For those electing to breastfeed, the patient should be provided with a breast pump to express and store the milk for subsequent bottle feeding. For mothers who elect to room in with the infant, a separation distance of 6 feet is recommended with an intervening barrier curtain. For COVID-19–positive mothers who elect breastfeeding, meticulous hand and face washing, continuous wearing of a mask, and cleansing of the breast prior to feeding needs to be maintained.

Restrictive visiting policies of no more than one visitor should be maintained. For severely or critically ill patients with COVID-19, it has been suggested that no visitors be allowed. As with other hospitalizations of COVID-19 patients, the HCW contact should be kept at a justifiable minimum to reduce the risk of transmission.
 

Protecting the obstetrician and other HCWs

Protecting the health of obstetricians and other HCWs is central to any successful strategy to fight the COVID-19 epidemic. For the individual obstetrician, careful attention to national and local hospital guidelines is required as these are rapidly evolving.

Physicians and their leadership must maintain an ongoing dialogue with hospital leadership to continually upgrade and optimize infection prevention and control measures, and to uphold best practices. The experience in Wuhan, China, illustrates the effectiveness of the proper use of PPE along with population control measures to reduce infections in HCWs. Prior to understanding the mechanism of virus transmission and using protective equipment, infection rates of 3%-29% were reported among HCWs. With the meticulous utilization of mitigation strategies and population control measures – including consistent use of PPE – the rate of infection of HCWs reportedly fell to zero.

In outpatient offices, all staff and HCWs should wear masks at all times and engage in social distancing and in frequent hand sanitization. Patients should be strongly encouraged to wear masks during office visits and on all other occasions when they will be in physical proximity to other individuals outside of the home.

Reports from epidemic areas describe transmission from household sources as a significant cause of HCW infection. The information emphasizes the need for ongoing vigilance and attention to sanitization measures even when at home with one’s family. An additional benefit is reduced risk of transmission from HCWs to family members.

Dr. Bahado-Singh is professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System.

References

1. Luo S et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.043.

2. Lechien JR et al. Eur Arch Otorhinolaryngol. 2020 Apr 6. doi: 10.1007/s00405-020-05965-1.

3. Breslin N et al. Am J Obstet Gynecol MFM. 2020 Apr 9. doi: 10.1016/j.ajogmf.2020.100118.

4. Zaigham M, Andersson O. Acta Obstet Gynecol Scand. 2020 Apr 7. doi: 10.1111/aogs.13867.

5. Di Mascio D et al. Am J Obstet Gynecol MFM. 2020 Mar 25. doi: 10.1016/j.ajogmf.2020.100107.

6. Ital J. Pediatr 2020;46(1) doi: 10.1186/s13052-020-0820-x. 

7. Int J Gynaecol Obstet. 2020;149(2):130-6. 

*This article was updated 5/6/2020. 

The meteoric rise in the number of test-positive and clinical cases of COVID-19 because of infection with the SARS coronavirus (SARS-CoV-2) in states and cities across the United States has added urgency to the efforts to develop protocols for hospital triage, admission, labor and delivery management, and other aspects of obstetrical care.

Emerging data suggest that, while SARS-CoV-2 is less lethal overall than the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) proved to be, it is significantly more contagious. Although a severe disease, the limited worldwide data so far available (as of early May) do not indicate that pregnant women are at greater risk of severe disease, compared with the general population. However, there remains a critical need for data on maternal and perinatal outcomes in women infected with SARS-CoV-2.

Multiple physiological changes in pregnancy, from reduced cell-based immune competence to changes in respiratory tract and pulmonary function – e.g., edema of the respiratory tract, increases in secretions and oxygen consumption, elevation of the diaphragm, and decrease in functional residual capacity – have historically contributed to worse obstetric outcomes in pregnant women who have had viral pneumonias. Furthermore, limited published experience with COVID-19 in China suggests worse perinatal outcomes in some affected pregnancies, including prematurity and perinatal death.

With evolution of the pandemic and accumulation of experience, it is expected that data-driven guidelines on assessment and management of infected pregnant women will contribute to improved maternal and perinatal outcomes. What is clear now, however, is that, without protecting the health of obstetricians and other health care workers, urgently needed gains in patient outcomes will not be realized.

Here are my recommendations, based on a currently limited body of literature on COVID-19 and other communicable viral respiratory disorders, as well my experience in the greater Detroit area, a COVID-19 hot spot.
 

Preparing for hospital evaluation and admission

The obstetric triage or labor and delivery (L&D) unit should be notified prior to the arrival of a patient suspected of or known to be infected with the virus. This will minimize staff exposure and allow sufficient time to prepare appropriate accommodations, equipment, and supplies for the patient’s care. Hospital infection control should be promptly notified by L&D of the expected arrival of such a patient. Placement ideally should be in a negative-pressure room, which allows outside air to flow into the room but prevents contaminated air from escaping. In the absence of a negative-pressure room, an infection isolation area should be utilized.

The patient and one accompanying support individual should wear either medical-grade masks brought from home or supplied upon entry to the hospital or homemade masks or bandanas. This will reduce the risk of viral transmission to hospital workers and other individuals encountered in the hospital prior to arriving in L&D. An ideal setup is to have separate entry areas, access corridors, and elevators for patients known or suspected to have COVID-19 infection. The patient and visitor should be expeditiously escorted to the prepared area for evaluation. Patients who are not known or suspected to be infected ideally should be tested.
 

Screening of patients & support individuals

Proper screening of patients and support individuals is critical to protecting both patients and staff in the L&D unit. This should include an expanded questionnaire that asks about disturbances of smell and taste and GI symptoms like loss of appetite – not only the more commonly queried symptoms of fever, shortness of breath, coughing, and exposure to someone who may have been ill.

Recent studies regarding presenting symptoms cast significant doubt, in fact, on the validity of patients with “asymptomatic COVID-19.” Over 15% of patients with confirmed infection in one published case series had solely GI symptoms and almost all had some digestive symptoms, for example, and almost 90% in another study had absent or reduced sense of smell and/or taste.^1,2 In fact, the use of the term “paucisymptomatic” rather than “asymptomatic” may be most appropriate.

Support individuals also should undergo temperature screening, ideally with laser noncontact thermometers on entry to the hospital or triage.
 

Visitor policy

The number of visitors/support individuals should be kept to a minimum to reduce transmission risk. The actual number will be determined by hospital or state policy, but up to one visitor in the labor room appears reasonable. Very strong individual justification should be required to exceed this threshold! The visitor should not only be screened for an expanded list of symptoms, but they also should be queried for underlying illnesses (e.g., diabetes, cardiovascular disease, significant lung disease, undergoing cancer therapy) as well as for age over 65 years, each of which increase the chances of severe COVID-19 disease should infection occur. The visitor should be informed of such risks and, especially when accompanying a patient with known or suspected COVID-19, provided the option of voluntarily revoking their visitor status. A visitor with known or suspected COVID-19 infection based on testing or screening should not be allowed into the L&D unit.

In addition, institutions may be considered to have obligations to the visitor/support person beyond screening. These include instructions in proper mask usage, hand washing, and limiting the touching of surfaces to lower infection risk.

“Visitor relays” where one visitor replaces another should be strongly discouraged. Visitors should similarly not be allowed to wander around the hospital (to use phones, for instance); transiting back and forth to obtain food and coffee should be kept to a strict minimum. For visitors accompanying COVID-19–-infected women, “visitor’s plates” provided by the hospital at reasonable cost is a much-preferred arrangement for obtaining meals during the course of the hospital stay. In addition, visitors should be sent out of the room during the performance of aerosolizing procedures.
 

Labor and delivery management

The successful management of patients with COVID-19 requires a rigorous infection control protocol informed by guidelines from national entities, such as the Centers for Disease Control and Prevention, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists, and by state health departments when available.

Strict limits on the number of obstetricians and other health care workers (HCWs) entering the patient’s room should be enforced and documented to minimize risk to the HCWs attending to patients who have a positive diagnosis or who are under investigation. Only in cases of demonstrable clinical benefit should repeat visits by the same or additional HCWs be permitted. Conventional and electronic tablets present an excellent opportunity for patient follow-up visits without room entry. In our institution, this has been successfully piloted in nonpregnant patients. Obstetricians and others caring for obstetrical patients – especially those who are infected or under investigation for infection – should always wear a properly fitted N95 mask.

Because patients with COVID-19 may have or go on to develop a constellation of organ abnormalities (e.g., cardiovascular, renal, pulmonary), it is vital that a standardized panel of baseline laboratory studies be developed for pregnant patients. This will minimize the need for repeated blood draws and other testing which may increase HCW exposure.

A negative screen based on nonreport of symptoms, lack of temperature elevation, and reported nonexposure to individuals with COVID-19 symptoms still has limitations in terms of disease detection. A recent report from a tertiary care hospital in New York City found that close to one-third of pregnant patients with confirmed COVID-19 admitted over a 2-week period had no viral symptoms or instructive history on initial admission.³ This is consistent with our clinical experience. Most importantly, therefore, routine quantitative reverse transcription polymerase chain reaction testing should be performed on all patients admitted to the L&D unit.

Given the reported variability in the accuracy of polymerase chain reaction testing induced by variable effectiveness of sampling techniques, stage of infection, and inherent test accuracy issues, symptomatic patients with a negative test should first obtain clearance from infectious disease specialists before isolation precautions are discontinued. Repeat testing in 24 hours, including testing of multiple sites, may subsequently yield a positive result in persistently symptomatic patients.
 

Intrapartum management

As much as possible, standard obstetric indications should guide the timing and route of delivery. In the case of a COVID-19–positive patient or a patient under investigation, nonobstetric factors may bear heavily on decision making, and management flexibility is of great value. For example, in cases of severe or critical disease status, evidence suggests that early delivery regardless of gestational age can improve maternal oxygenation; this supports the liberal use of C-sections in these circumstances. In addition, shortening labor length as well as duration of hospitalization may be expected to reduce the risk of transmission to HCWs, other staff, and other patients.

High rates of cesarean delivery unsurprisingly have been reported thus far: One review of 108 case reports and series of test-positive COVID-19 pregnancies found a 92% C-section rate, and another review and meta-analysis of studies of SARS, MERS, and COVID-19 during pregnancy similarly found that the majority of patients – 84% across all coronavirus infections and 91% in COVID-19 pregnancies – were delivered by C-section.4,5 Given these high rates of cesarean deliveries, the early placement of neuraxial anesthesia while the patient is stable appears to be prudent and obviates the need for intubation, the latter of which is associated with increased aerosol generation and increased virus transmission risk.

Strict protocols for the optimal protection of staff should be observed, including proper personal protective equipment (PPE) protection. Protocols have been detailed in various guidelines and publications; they include the wearing of shoe covers, gowns, N95 masks, goggles, face shields, and two layers of gloves.

For institutions that currently do not offer routine COVID-19 testing to pregnant patients – especially those in areas of outbreaks – N95 masks and eye protection should still be provided to all HCWs involved in the intrapartum management of untested asymptomatic patients, particularly those in the active phase of labor. This protection is justified given the limitations of symptom- and history-based screening and the not-uncommon experience of the patient with a negative screen who subsequently develops the clinical syndrome.

Obstetric management of labor requires close patient contact that potentially elevates the risk of contamination and infection. During the active stage of labor, patient shouting, rapid mouth breathing, and other behaviors inherent to labor all increase the risk of aerosolization of oronasal secretions. In addition, nasal-prong oxygen administration is believed to independently increase the risk of aerosolization of secretions. The casual practice of nasal oxygen application should thus be discontinued and, where felt to be absolutely necessary, a mask should be worn on top of the prongs.

Regarding operative delivery, each participating obstetric surgeon should observe guidelines and recommendations of governing national organizations and professional groups – including the American College of Surgeons – regarding the safe conduct of operations on patients with COVID-19. Written guidelines should be tailored as needed to the performance of C-sections and readily available in L&D. Drills and simulations are generally valuable, and expertise and support should always be available in the labor room to assist with donning and doffing of PPE.
 

Postpartum care

Expeditious separation of the COVID-19–positive mother from her infant is recommended, including avoidance of delayed cord clamping because of insufficient evidence of benefit to the infant. Insufficient evidence exists to support vertical transmission, but the possibility of maternal-infant transmission is clinically accepted based on small case reports of infection in a neonate at 30 hours of life and in infants of mothers with suspected or confirmed COVID-19.6,7 Accordingly, it is recommended that the benefit of early infant separation should be discussed with the mother. If approved, the infant should be kept in a separate isolation area and observed.

There is no evidence of breast milk transmission of the virus. For those electing to breastfeed, the patient should be provided with a breast pump to express and store the milk for subsequent bottle feeding. For mothers who elect to room in with the infant, a separation distance of 6 feet is recommended with an intervening barrier curtain. For COVID-19–positive mothers who elect breastfeeding, meticulous hand and face washing, continuous wearing of a mask, and cleansing of the breast prior to feeding needs to be maintained.

Restrictive visiting policies of no more than one visitor should be maintained. For severely or critically ill patients with COVID-19, it has been suggested that no visitors be allowed. As with other hospitalizations of COVID-19 patients, the HCW contact should be kept at a justifiable minimum to reduce the risk of transmission.
 

Protecting the obstetrician and other HCWs

Protecting the health of obstetricians and other HCWs is central to any successful strategy to fight the COVID-19 epidemic. For the individual obstetrician, careful attention to national and local hospital guidelines is required as these are rapidly evolving.

Physicians and their leadership must maintain an ongoing dialogue with hospital leadership to continually upgrade and optimize infection prevention and control measures, and to uphold best practices. The experience in Wuhan, China, illustrates the effectiveness of the proper use of PPE along with population control measures to reduce infections in HCWs. Prior to understanding the mechanism of virus transmission and using protective equipment, infection rates of 3%-29% were reported among HCWs. With the meticulous utilization of mitigation strategies and population control measures – including consistent use of PPE – the rate of infection of HCWs reportedly fell to zero.

In outpatient offices, all staff and HCWs should wear masks at all times and engage in social distancing and in frequent hand sanitization. Patients should be strongly encouraged to wear masks during office visits and on all other occasions when they will be in physical proximity to other individuals outside of the home.

Reports from epidemic areas describe transmission from household sources as a significant cause of HCW infection. The information emphasizes the need for ongoing vigilance and attention to sanitization measures even when at home with one’s family. An additional benefit is reduced risk of transmission from HCWs to family members.

Dr. Bahado-Singh is professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System.

References

1. Luo S et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.043.

2. Lechien JR et al. Eur Arch Otorhinolaryngol. 2020 Apr 6. doi: 10.1007/s00405-020-05965-1.

3. Breslin N et al. Am J Obstet Gynecol MFM. 2020 Apr 9. doi: 10.1016/j.ajogmf.2020.100118.

4. Zaigham M, Andersson O. Acta Obstet Gynecol Scand. 2020 Apr 7. doi: 10.1111/aogs.13867.

5. Di Mascio D et al. Am J Obstet Gynecol MFM. 2020 Mar 25. doi: 10.1016/j.ajogmf.2020.100107.

6. Ital J. Pediatr 2020;46(1) doi: 10.1186/s13052-020-0820-x. 

7. Int J Gynaecol Obstet. 2020;149(2):130-6. 

*This article was updated 5/6/2020. 

The meteoric rise in the number of test-positive and clinical cases of COVID-19 because of infection with the SARS coronavirus (SARS-CoV-2) in states and cities across the United States has added urgency to the efforts to develop protocols for hospital triage, admission, labor and delivery management, and other aspects of obstetrical care.

Emerging data suggest that, while SARS-CoV-2 is less lethal overall than the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) proved to be, it is significantly more contagious. Although a severe disease, the limited worldwide data so far available (as of early May) do not indicate that pregnant women are at greater risk of severe disease, compared with the general population. However, there remains a critical need for data on maternal and perinatal outcomes in women infected with SARS-CoV-2.

Multiple physiological changes in pregnancy, from reduced cell-based immune competence to changes in respiratory tract and pulmonary function – e.g., edema of the respiratory tract, increases in secretions and oxygen consumption, elevation of the diaphragm, and decrease in functional residual capacity – have historically contributed to worse obstetric outcomes in pregnant women who have had viral pneumonias. Furthermore, limited published experience with COVID-19 in China suggests worse perinatal outcomes in some affected pregnancies, including prematurity and perinatal death.

With evolution of the pandemic and accumulation of experience, it is expected that data-driven guidelines on assessment and management of infected pregnant women will contribute to improved maternal and perinatal outcomes. What is clear now, however, is that, without protecting the health of obstetricians and other health care workers, urgently needed gains in patient outcomes will not be realized.

Here are my recommendations, based on a currently limited body of literature on COVID-19 and other communicable viral respiratory disorders, as well my experience in the greater Detroit area, a COVID-19 hot spot.
 

Preparing for hospital evaluation and admission

The obstetric triage or labor and delivery (L&D) unit should be notified prior to the arrival of a patient suspected of or known to be infected with the virus. This will minimize staff exposure and allow sufficient time to prepare appropriate accommodations, equipment, and supplies for the patient’s care. Hospital infection control should be promptly notified by L&D of the expected arrival of such a patient. Placement ideally should be in a negative-pressure room, which allows outside air to flow into the room but prevents contaminated air from escaping. In the absence of a negative-pressure room, an infection isolation area should be utilized.

The patient and one accompanying support individual should wear either medical-grade masks brought from home or supplied upon entry to the hospital or homemade masks or bandanas. This will reduce the risk of viral transmission to hospital workers and other individuals encountered in the hospital prior to arriving in L&D. An ideal setup is to have separate entry areas, access corridors, and elevators for patients known or suspected to have COVID-19 infection. The patient and visitor should be expeditiously escorted to the prepared area for evaluation. Patients who are not known or suspected to be infected ideally should be tested.
 

Screening of patients & support individuals

Proper screening of patients and support individuals is critical to protecting both patients and staff in the L&D unit. This should include an expanded questionnaire that asks about disturbances of smell and taste and GI symptoms like loss of appetite – not only the more commonly queried symptoms of fever, shortness of breath, coughing, and exposure to someone who may have been ill.

Recent studies regarding presenting symptoms cast significant doubt, in fact, on the validity of patients with “asymptomatic COVID-19.” Over 15% of patients with confirmed infection in one published case series had solely GI symptoms and almost all had some digestive symptoms, for example, and almost 90% in another study had absent or reduced sense of smell and/or taste.^1,2 In fact, the use of the term “paucisymptomatic” rather than “asymptomatic” may be most appropriate.

Support individuals also should undergo temperature screening, ideally with laser noncontact thermometers on entry to the hospital or triage.
 

Visitor policy

The number of visitors/support individuals should be kept to a minimum to reduce transmission risk. The actual number will be determined by hospital or state policy, but up to one visitor in the labor room appears reasonable. Very strong individual justification should be required to exceed this threshold! The visitor should not only be screened for an expanded list of symptoms, but they also should be queried for underlying illnesses (e.g., diabetes, cardiovascular disease, significant lung disease, undergoing cancer therapy) as well as for age over 65 years, each of which increase the chances of severe COVID-19 disease should infection occur. The visitor should be informed of such risks and, especially when accompanying a patient with known or suspected COVID-19, provided the option of voluntarily revoking their visitor status. A visitor with known or suspected COVID-19 infection based on testing or screening should not be allowed into the L&D unit.

In addition, institutions may be considered to have obligations to the visitor/support person beyond screening. These include instructions in proper mask usage, hand washing, and limiting the touching of surfaces to lower infection risk.

“Visitor relays” where one visitor replaces another should be strongly discouraged. Visitors should similarly not be allowed to wander around the hospital (to use phones, for instance); transiting back and forth to obtain food and coffee should be kept to a strict minimum. For visitors accompanying COVID-19–-infected women, “visitor’s plates” provided by the hospital at reasonable cost is a much-preferred arrangement for obtaining meals during the course of the hospital stay. In addition, visitors should be sent out of the room during the performance of aerosolizing procedures.
 

Labor and delivery management

The successful management of patients with COVID-19 requires a rigorous infection control protocol informed by guidelines from national entities, such as the Centers for Disease Control and Prevention, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists, and by state health departments when available.

Strict limits on the number of obstetricians and other health care workers (HCWs) entering the patient’s room should be enforced and documented to minimize risk to the HCWs attending to patients who have a positive diagnosis or who are under investigation. Only in cases of demonstrable clinical benefit should repeat visits by the same or additional HCWs be permitted. Conventional and electronic tablets present an excellent opportunity for patient follow-up visits without room entry. In our institution, this has been successfully piloted in nonpregnant patients. Obstetricians and others caring for obstetrical patients – especially those who are infected or under investigation for infection – should always wear a properly fitted N95 mask.

Because patients with COVID-19 may have or go on to develop a constellation of organ abnormalities (e.g., cardiovascular, renal, pulmonary), it is vital that a standardized panel of baseline laboratory studies be developed for pregnant patients. This will minimize the need for repeated blood draws and other testing which may increase HCW exposure.

A negative screen based on nonreport of symptoms, lack of temperature elevation, and reported nonexposure to individuals with COVID-19 symptoms still has limitations in terms of disease detection. A recent report from a tertiary care hospital in New York City found that close to one-third of pregnant patients with confirmed COVID-19 admitted over a 2-week period had no viral symptoms or instructive history on initial admission.³ This is consistent with our clinical experience. Most importantly, therefore, routine quantitative reverse transcription polymerase chain reaction testing should be performed on all patients admitted to the L&D unit.

Given the reported variability in the accuracy of polymerase chain reaction testing induced by variable effectiveness of sampling techniques, stage of infection, and inherent test accuracy issues, symptomatic patients with a negative test should first obtain clearance from infectious disease specialists before isolation precautions are discontinued. Repeat testing in 24 hours, including testing of multiple sites, may subsequently yield a positive result in persistently symptomatic patients.
 

Intrapartum management

As much as possible, standard obstetric indications should guide the timing and route of delivery. In the case of a COVID-19–positive patient or a patient under investigation, nonobstetric factors may bear heavily on decision making, and management flexibility is of great value. For example, in cases of severe or critical disease status, evidence suggests that early delivery regardless of gestational age can improve maternal oxygenation; this supports the liberal use of C-sections in these circumstances. In addition, shortening labor length as well as duration of hospitalization may be expected to reduce the risk of transmission to HCWs, other staff, and other patients.

High rates of cesarean delivery unsurprisingly have been reported thus far: One review of 108 case reports and series of test-positive COVID-19 pregnancies found a 92% C-section rate, and another review and meta-analysis of studies of SARS, MERS, and COVID-19 during pregnancy similarly found that the majority of patients – 84% across all coronavirus infections and 91% in COVID-19 pregnancies – were delivered by C-section.4,5 Given these high rates of cesarean deliveries, the early placement of neuraxial anesthesia while the patient is stable appears to be prudent and obviates the need for intubation, the latter of which is associated with increased aerosol generation and increased virus transmission risk.

Strict protocols for the optimal protection of staff should be observed, including proper personal protective equipment (PPE) protection. Protocols have been detailed in various guidelines and publications; they include the wearing of shoe covers, gowns, N95 masks, goggles, face shields, and two layers of gloves.

For institutions that currently do not offer routine COVID-19 testing to pregnant patients – especially those in areas of outbreaks – N95 masks and eye protection should still be provided to all HCWs involved in the intrapartum management of untested asymptomatic patients, particularly those in the active phase of labor. This protection is justified given the limitations of symptom- and history-based screening and the not-uncommon experience of the patient with a negative screen who subsequently develops the clinical syndrome.

Obstetric management of labor requires close patient contact that potentially elevates the risk of contamination and infection. During the active stage of labor, patient shouting, rapid mouth breathing, and other behaviors inherent to labor all increase the risk of aerosolization of oronasal secretions. In addition, nasal-prong oxygen administration is believed to independently increase the risk of aerosolization of secretions. The casual practice of nasal oxygen application should thus be discontinued and, where felt to be absolutely necessary, a mask should be worn on top of the prongs.

Regarding operative delivery, each participating obstetric surgeon should observe guidelines and recommendations of governing national organizations and professional groups – including the American College of Surgeons – regarding the safe conduct of operations on patients with COVID-19. Written guidelines should be tailored as needed to the performance of C-sections and readily available in L&D. Drills and simulations are generally valuable, and expertise and support should always be available in the labor room to assist with donning and doffing of PPE.
 

Postpartum care

Expeditious separation of the COVID-19–positive mother from her infant is recommended, including avoidance of delayed cord clamping because of insufficient evidence of benefit to the infant. Insufficient evidence exists to support vertical transmission, but the possibility of maternal-infant transmission is clinically accepted based on small case reports of infection in a neonate at 30 hours of life and in infants of mothers with suspected or confirmed COVID-19.6,7 Accordingly, it is recommended that the benefit of early infant separation should be discussed with the mother. If approved, the infant should be kept in a separate isolation area and observed.

There is no evidence of breast milk transmission of the virus. For those electing to breastfeed, the patient should be provided with a breast pump to express and store the milk for subsequent bottle feeding. For mothers who elect to room in with the infant, a separation distance of 6 feet is recommended with an intervening barrier curtain. For COVID-19–positive mothers who elect breastfeeding, meticulous hand and face washing, continuous wearing of a mask, and cleansing of the breast prior to feeding needs to be maintained.

Restrictive visiting policies of no more than one visitor should be maintained. For severely or critically ill patients with COVID-19, it has been suggested that no visitors be allowed. As with other hospitalizations of COVID-19 patients, the HCW contact should be kept at a justifiable minimum to reduce the risk of transmission.
 

Protecting the obstetrician and other HCWs

Protecting the health of obstetricians and other HCWs is central to any successful strategy to fight the COVID-19 epidemic. For the individual obstetrician, careful attention to national and local hospital guidelines is required as these are rapidly evolving.

Physicians and their leadership must maintain an ongoing dialogue with hospital leadership to continually upgrade and optimize infection prevention and control measures, and to uphold best practices. The experience in Wuhan, China, illustrates the effectiveness of the proper use of PPE along with population control measures to reduce infections in HCWs. Prior to understanding the mechanism of virus transmission and using protective equipment, infection rates of 3%-29% were reported among HCWs. With the meticulous utilization of mitigation strategies and population control measures – including consistent use of PPE – the rate of infection of HCWs reportedly fell to zero.

In outpatient offices, all staff and HCWs should wear masks at all times and engage in social distancing and in frequent hand sanitization. Patients should be strongly encouraged to wear masks during office visits and on all other occasions when they will be in physical proximity to other individuals outside of the home.

Reports from epidemic areas describe transmission from household sources as a significant cause of HCW infection. The information emphasizes the need for ongoing vigilance and attention to sanitization measures even when at home with one’s family. An additional benefit is reduced risk of transmission from HCWs to family members.

Dr. Bahado-Singh is professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System.

References

1. Luo S et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.043.

2. Lechien JR et al. Eur Arch Otorhinolaryngol. 2020 Apr 6. doi: 10.1007/s00405-020-05965-1.

3. Breslin N et al. Am J Obstet Gynecol MFM. 2020 Apr 9. doi: 10.1016/j.ajogmf.2020.100118.

4. Zaigham M, Andersson O. Acta Obstet Gynecol Scand. 2020 Apr 7. doi: 10.1111/aogs.13867.

5. Di Mascio D et al. Am J Obstet Gynecol MFM. 2020 Mar 25. doi: 10.1016/j.ajogmf.2020.100107.

6. Ital J. Pediatr 2020;46(1) doi: 10.1186/s13052-020-0820-x. 

7. Int J Gynaecol Obstet. 2020;149(2):130-6. 

*This article was updated 5/6/2020. 

The identification of the SARS coronavirus (SARS-CoV-2) and emergence of the associated infectious respiratory disease, COVID-19, in late 2019 catapulted the citizens of the world, especially those in the health care professions, into an era of considerable uncertainty. At this moment in human history, calm reassurance – founded in fact and evidence – seems its greatest need. Much of the focus within the biomedical community has been on containment, prevention, and treatment of this highly contagious and, for some, extremely virulent disease.

However, for ob.gyns on the front lines of the COVID-19 fight, there is the additional challenge of caring for at least two patients simultaneously: the mother and her unborn baby. Studies in mother-baby dyads, while being published at an incredible pace, are still quite scarce. In addition, published reports are limited by the small sample size of the patient population (many are single-case reports), lack of uniformity in the timing and types of clinical samples collected, testing delays, and varying isolation protocols in cases where the mother has confirmed SARS-CoV-2.

Five months into a pandemic that has swept the world, we still know very little about COVID-19 infection in the general population, let alone the obstetric one. We do not know if having and resolving COVID-19 infection provides any long-term protection against future disease. We do not know if vertical transmission of SARS-CoV-2 occurs. We do not know if maternal infection confers any immunologic benefit to the neonate. The list goes on.

What we do know is that taking extra precautions works. Use of personal protective equipment saves health care practitioner and patient lives. Prohibiting or restricting visitors to only one person in hospitals reduces risk of transmission to vulnerable patients. Shifting to fewer in-office prenatal consults decreases a pregnant woman’s potential exposure to the virus.

Additionally, we know that leading with compassion is vital to easing patient – and practitioner – anxiety and stress. Most importantly, we know that people are extraordinarily resilient, especially when it comes to safeguarding the health of their families.

To address some of the major concerns that many ob.gyns. have regarding their risk of coronavirus exposure when caring for patients, we have invited Ray Bahado-Singh, MD, professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System, who works in a suburb of Detroit, one of our nation’s COVID-19 hot spots.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The identification of the SARS coronavirus (SARS-CoV-2) and emergence of the associated infectious respiratory disease, COVID-19, in late 2019 catapulted the citizens of the world, especially those in the health care professions, into an era of considerable uncertainty. At this moment in human history, calm reassurance – founded in fact and evidence – seems its greatest need. Much of the focus within the biomedical community has been on containment, prevention, and treatment of this highly contagious and, for some, extremely virulent disease.

However, for ob.gyns on the front lines of the COVID-19 fight, there is the additional challenge of caring for at least two patients simultaneously: the mother and her unborn baby. Studies in mother-baby dyads, while being published at an incredible pace, are still quite scarce. In addition, published reports are limited by the small sample size of the patient population (many are single-case reports), lack of uniformity in the timing and types of clinical samples collected, testing delays, and varying isolation protocols in cases where the mother has confirmed SARS-CoV-2.

Five months into a pandemic that has swept the world, we still know very little about COVID-19 infection in the general population, let alone the obstetric one. We do not know if having and resolving COVID-19 infection provides any long-term protection against future disease. We do not know if vertical transmission of SARS-CoV-2 occurs. We do not know if maternal infection confers any immunologic benefit to the neonate. The list goes on.

What we do know is that taking extra precautions works. Use of personal protective equipment saves health care practitioner and patient lives. Prohibiting or restricting visitors to only one person in hospitals reduces risk of transmission to vulnerable patients. Shifting to fewer in-office prenatal consults decreases a pregnant woman’s potential exposure to the virus.

Additionally, we know that leading with compassion is vital to easing patient – and practitioner – anxiety and stress. Most importantly, we know that people are extraordinarily resilient, especially when it comes to safeguarding the health of their families.

To address some of the major concerns that many ob.gyns. have regarding their risk of coronavirus exposure when caring for patients, we have invited Ray Bahado-Singh, MD, professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System, who works in a suburb of Detroit, one of our nation’s COVID-19 hot spots.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

The identification of the SARS coronavirus (SARS-CoV-2) and emergence of the associated infectious respiratory disease, COVID-19, in late 2019 catapulted the citizens of the world, especially those in the health care professions, into an era of considerable uncertainty. At this moment in human history, calm reassurance – founded in fact and evidence – seems its greatest need. Much of the focus within the biomedical community has been on containment, prevention, and treatment of this highly contagious and, for some, extremely virulent disease.

However, for ob.gyns on the front lines of the COVID-19 fight, there is the additional challenge of caring for at least two patients simultaneously: the mother and her unborn baby. Studies in mother-baby dyads, while being published at an incredible pace, are still quite scarce. In addition, published reports are limited by the small sample size of the patient population (many are single-case reports), lack of uniformity in the timing and types of clinical samples collected, testing delays, and varying isolation protocols in cases where the mother has confirmed SARS-CoV-2.

Five months into a pandemic that has swept the world, we still know very little about COVID-19 infection in the general population, let alone the obstetric one. We do not know if having and resolving COVID-19 infection provides any long-term protection against future disease. We do not know if vertical transmission of SARS-CoV-2 occurs. We do not know if maternal infection confers any immunologic benefit to the neonate. The list goes on.

What we do know is that taking extra precautions works. Use of personal protective equipment saves health care practitioner and patient lives. Prohibiting or restricting visitors to only one person in hospitals reduces risk of transmission to vulnerable patients. Shifting to fewer in-office prenatal consults decreases a pregnant woman’s potential exposure to the virus.

Additionally, we know that leading with compassion is vital to easing patient – and practitioner – anxiety and stress. Most importantly, we know that people are extraordinarily resilient, especially when it comes to safeguarding the health of their families.

To address some of the major concerns that many ob.gyns. have regarding their risk of coronavirus exposure when caring for patients, we have invited Ray Bahado-Singh, MD, professor and chair of obstetrics and gynecology at Oakland University, Rochester, Mich., and health system chair for obstetrics and gynecology at Beaumont Health System, who works in a suburb of Detroit, one of our nation’s COVID-19 hot spots.

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

[email protected]

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

[email protected]

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

[email protected]

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

[email protected]

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

[email protected]

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

[email protected]

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

[email protected]

Starting treatment for relapsing-remitting multiple sclerosis (MS) with high-efficacy therapy (HET) is associated with lower long-term disability compared with a step-wise increase to reach more aggressive treatment later, new research suggests. However, there is a trade-off: In this study of nearly 300 patients, those treated with initial HET experienced more disease activity in the first 2 years than other participants.

The HET benefit emerged between 2 and 10 years into the study. For example, the mean Expanded Disability Status Scale (EDSS) scores were significantly lower at 6 years in the early, aggressive treatment group than in the later HET group (2.4 vs 3.3, respectively).

“Treatment decisions made around the time of diagnosis will affect long-term outcomes,” said lead author Anna He, MBBS, currently with the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, and the UCL Queen Square Institute of Neurology in London.

Using the most efficacious disease-modifying therapies from the start minimizes disability, “whereas those patients escalating to high-efficacy disease-modifying therapies later do not seem to catch up to those who commenced earlier,” Dr. He said.

“Patients and clinicians should be aware of this when choosing treatment in early MS,” she added.

This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Patient-centered outcome

Instead of measures of brain volume, lesion count, serum neurofilament, or other biomarkers that are mainly of interest to clinicians and scientists, “the main outcome of interest to our patients is their disability,” Dr. He said. “The first question they ask at diagnosis is usually along the lines of: ‘What will my disability be in 10 years?’ ”

“This is what matters to patients and is fundamentally what motivated this study,” Dr. He added.

The investigators searched international MS registries for patients with relapsing-remitting MS starting HET, which included rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab.

They compared 117 participants who started HET within the first 2 years of clinical disease onset (the early group) with 181 participants who started HET after more than 4 years (the late group). All were followed for a median of 7.4 years (range, 6.4 to 8.6 years).

Difference in EDSS scores from baseline was the primary outcome. Both cohorts began the study with a mean EDSS score of 2.4, but between-group differences were significant at 10 years.

The secondary outcome of cumulative hazard of disability progression was higher in the early-treatment group from baseline to 2 years. Between the period of 2 and 10 years, the inverse was true.

In patients with highly active MS, “early exposure to high efficacy therapies is recommended,” Dr. He noted.

“We can already affect our patients’ lives enormously by utilizing our current toolbox in the most optimal way. It is our task to optimize this in a data-driven manner.”

Going forward, Dr. He plans to look at other outcomes, including patient-reported quality of life and health economic measures, and to take a different approach to future research.

Rather than assess MS outcomes from a disease-biology perspective, “I will be looking at MS outcomes from the perspective of its key stakeholders—the individual and society,” and the factors that influence them, Dr. He said.
 

Confirmatory evidence?

Commenting on the findings, Robert Gross, MD, a neurologist at the Rocky Mountain MS Center at the University of Colorado Denver in Aurora, said it is “hard to believe we are still having this debate” about earlier versus later HET.

There are now “numerous studies, including head-to-head trials and large cohort studies, showing superiority of highly efficacious agents to older disease-modifying therapies of more limited efficacy, as well as better outcomes with early versus delayed use of high-efficacy therapy,” said Dr. Gross, who was not involved with the current research.

“This study further adds to the evidence that we should be preferentially starting folks with relapsing-remitting MS right away on high-efficacy therapy, rather than waiting for relapses and disease progression to occur,” he added.

Drs. He and Gross have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Starting treatment for relapsing-remitting multiple sclerosis (MS) with high-efficacy therapy (HET) is associated with lower long-term disability compared with a step-wise increase to reach more aggressive treatment later, new research suggests. However, there is a trade-off: In this study of nearly 300 patients, those treated with initial HET experienced more disease activity in the first 2 years than other participants.

The HET benefit emerged between 2 and 10 years into the study. For example, the mean Expanded Disability Status Scale (EDSS) scores were significantly lower at 6 years in the early, aggressive treatment group than in the later HET group (2.4 vs 3.3, respectively).

“Treatment decisions made around the time of diagnosis will affect long-term outcomes,” said lead author Anna He, MBBS, currently with the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, and the UCL Queen Square Institute of Neurology in London.

Using the most efficacious disease-modifying therapies from the start minimizes disability, “whereas those patients escalating to high-efficacy disease-modifying therapies later do not seem to catch up to those who commenced earlier,” Dr. He said.

“Patients and clinicians should be aware of this when choosing treatment in early MS,” she added.

This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Patient-centered outcome

Instead of measures of brain volume, lesion count, serum neurofilament, or other biomarkers that are mainly of interest to clinicians and scientists, “the main outcome of interest to our patients is their disability,” Dr. He said. “The first question they ask at diagnosis is usually along the lines of: ‘What will my disability be in 10 years?’ ”

“This is what matters to patients and is fundamentally what motivated this study,” Dr. He added.

The investigators searched international MS registries for patients with relapsing-remitting MS starting HET, which included rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab.

They compared 117 participants who started HET within the first 2 years of clinical disease onset (the early group) with 181 participants who started HET after more than 4 years (the late group). All were followed for a median of 7.4 years (range, 6.4 to 8.6 years).

Difference in EDSS scores from baseline was the primary outcome. Both cohorts began the study with a mean EDSS score of 2.4, but between-group differences were significant at 10 years.

The secondary outcome of cumulative hazard of disability progression was higher in the early-treatment group from baseline to 2 years. Between the period of 2 and 10 years, the inverse was true.

In patients with highly active MS, “early exposure to high efficacy therapies is recommended,” Dr. He noted.

“We can already affect our patients’ lives enormously by utilizing our current toolbox in the most optimal way. It is our task to optimize this in a data-driven manner.”

Going forward, Dr. He plans to look at other outcomes, including patient-reported quality of life and health economic measures, and to take a different approach to future research.

Rather than assess MS outcomes from a disease-biology perspective, “I will be looking at MS outcomes from the perspective of its key stakeholders—the individual and society,” and the factors that influence them, Dr. He said.
 

Confirmatory evidence?

Commenting on the findings, Robert Gross, MD, a neurologist at the Rocky Mountain MS Center at the University of Colorado Denver in Aurora, said it is “hard to believe we are still having this debate” about earlier versus later HET.

There are now “numerous studies, including head-to-head trials and large cohort studies, showing superiority of highly efficacious agents to older disease-modifying therapies of more limited efficacy, as well as better outcomes with early versus delayed use of high-efficacy therapy,” said Dr. Gross, who was not involved with the current research.

“This study further adds to the evidence that we should be preferentially starting folks with relapsing-remitting MS right away on high-efficacy therapy, rather than waiting for relapses and disease progression to occur,” he added.

Drs. He and Gross have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Starting treatment for relapsing-remitting multiple sclerosis (MS) with high-efficacy therapy (HET) is associated with lower long-term disability compared with a step-wise increase to reach more aggressive treatment later, new research suggests. However, there is a trade-off: In this study of nearly 300 patients, those treated with initial HET experienced more disease activity in the first 2 years than other participants.

The HET benefit emerged between 2 and 10 years into the study. For example, the mean Expanded Disability Status Scale (EDSS) scores were significantly lower at 6 years in the early, aggressive treatment group than in the later HET group (2.4 vs 3.3, respectively).

“Treatment decisions made around the time of diagnosis will affect long-term outcomes,” said lead author Anna He, MBBS, currently with the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, and the UCL Queen Square Institute of Neurology in London.

Using the most efficacious disease-modifying therapies from the start minimizes disability, “whereas those patients escalating to high-efficacy disease-modifying therapies later do not seem to catch up to those who commenced earlier,” Dr. He said.

“Patients and clinicians should be aware of this when choosing treatment in early MS,” she added.

This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Patient-centered outcome

Instead of measures of brain volume, lesion count, serum neurofilament, or other biomarkers that are mainly of interest to clinicians and scientists, “the main outcome of interest to our patients is their disability,” Dr. He said. “The first question they ask at diagnosis is usually along the lines of: ‘What will my disability be in 10 years?’ ”

“This is what matters to patients and is fundamentally what motivated this study,” Dr. He added.

The investigators searched international MS registries for patients with relapsing-remitting MS starting HET, which included rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab.

They compared 117 participants who started HET within the first 2 years of clinical disease onset (the early group) with 181 participants who started HET after more than 4 years (the late group). All were followed for a median of 7.4 years (range, 6.4 to 8.6 years).

Difference in EDSS scores from baseline was the primary outcome. Both cohorts began the study with a mean EDSS score of 2.4, but between-group differences were significant at 10 years.

The secondary outcome of cumulative hazard of disability progression was higher in the early-treatment group from baseline to 2 years. Between the period of 2 and 10 years, the inverse was true.

In patients with highly active MS, “early exposure to high efficacy therapies is recommended,” Dr. He noted.

“We can already affect our patients’ lives enormously by utilizing our current toolbox in the most optimal way. It is our task to optimize this in a data-driven manner.”

Going forward, Dr. He plans to look at other outcomes, including patient-reported quality of life and health economic measures, and to take a different approach to future research.

Rather than assess MS outcomes from a disease-biology perspective, “I will be looking at MS outcomes from the perspective of its key stakeholders—the individual and society,” and the factors that influence them, Dr. He said.
 

Confirmatory evidence?

Commenting on the findings, Robert Gross, MD, a neurologist at the Rocky Mountain MS Center at the University of Colorado Denver in Aurora, said it is “hard to believe we are still having this debate” about earlier versus later HET.

There are now “numerous studies, including head-to-head trials and large cohort studies, showing superiority of highly efficacious agents to older disease-modifying therapies of more limited efficacy, as well as better outcomes with early versus delayed use of high-efficacy therapy,” said Dr. Gross, who was not involved with the current research.

“This study further adds to the evidence that we should be preferentially starting folks with relapsing-remitting MS right away on high-efficacy therapy, rather than waiting for relapses and disease progression to occur,” he added.

Drs. He and Gross have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Like many in the health care field, I have found it hard to watch the news over these past couple of months when it seems that almost every story is about COVID-19 or its repercussions. Luckily, I have two young daughters who “encourage” me to listen to the Frozen 2 soundtrack instead of putting on the evening news when I get home from work. Still, news manages to seep through my defenses. As I scrolled through some headlines recently, I learned of the death of musician Adam Schlesinger from COVID-19. He wasn’t a household name, but his death still hit me in unexpected ways.

I started internship in late June 2005, in a city (Portland, Ore.) about as different from my previous home (Dallas) as any two places can possibly be. I think the day before internship started still ranks as the most nervous of my life. I’m not sure how I slept at all that night, but somehow I did and arrived at the Portland Veterans Affairs Hospital the following morning to start my new career.

And then … nothing happened. Early on that first day, the electronic medical records crashed, and no patients were admitted during our time on “short call.” My upper level resident took care of the one or two established patients on the team (both discharged), so I ended the day with records that would not be broken during the remainder of my residency: 0 notes written, 0 patients seen. Perhaps the most successful first day that any intern, anywhere has ever had, although it prepared me quite poorly for all the subsequent days.

Since I had some time on my hands, I made the 20-minute walk to one of my new hometown’s record stores where Fountains of Wayne (FOW) was playing an acoustic in-store set. Their album from a few years prior, “Welcome Interstate Managers,” was in heavy rotation when I made the drive from Dallas to Portland. It was (and is) a great album for long drives – melodic, catchy, and (mostly) up-tempo. Adam and the band’s singer, Chris Collingwood, played several songs that night on the store’s stage. Then they headed out to the next city, and I headed back home and on to many far-busier days of residency.

We would cross paths again a decade later. I moved back to Texas and became a hospitalist. It turns out that, if you have enough hospitalists of a certain age and if enough of those hospitalists have unearned confidence in their musical ability, then a covers band will undoubtedly be formed. And so, it happened here in San Antonio. We were not selective in our song choices – we played songs from every decade of the last 50 years, bands as popular as the Beatles and as indie as the Rentals. And we played some FOW.

Our band (which will go nameless here so that our YouTube recordings are more difficult to find) played a grand total of one gig during our years of intermittent practicing. That one gig was my wedding rehearsal dinner and the penultimate song we played was “Stacy’s Mom,” which is notable for being both FOW’s biggest hit and a completely inappropriate song to play at a wedding rehearsal dinner. The crowd was probably around the same size as the one that had seen Adam and Chris play in Portland 10 years prior. I don’t think the applause we received was quite as genuine or deserved, though.

After Adam and Chris played their gig, there was an autograph session and I took home a signed poster. Last year, I decided to take it out of storage and hang it in my office. The date of the show and the first day of my physician career, a date now nearly 15 years ago, is written in psychedelic typography at the bottom. The store that I went to that day is no longer there, a victim of progress like so many other record stores across the country. Another location of the same store is still open in Portland. I hope that it and all the other small book and music stores across the country can survive this current crisis, but I know that many will not.

So, here’s to you Adam, and to all the others who have lost their lives to this terrible illness. As a small token of remembrance, I’ll be playing some Fountains of Wayne on the drive home tonight. It’s not quite the same as playing it on a cross-country drive, but hopefully, we will all be able to do that again soon.

Dr. Sehgal is a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System and UT-Health San Antonio. He is a member of the editorial advisory board for The Hospitalist.

Like many in the health care field, I have found it hard to watch the news over these past couple of months when it seems that almost every story is about COVID-19 or its repercussions. Luckily, I have two young daughters who “encourage” me to listen to the Frozen 2 soundtrack instead of putting on the evening news when I get home from work. Still, news manages to seep through my defenses. As I scrolled through some headlines recently, I learned of the death of musician Adam Schlesinger from COVID-19. He wasn’t a household name, but his death still hit me in unexpected ways.

I started internship in late June 2005, in a city (Portland, Ore.) about as different from my previous home (Dallas) as any two places can possibly be. I think the day before internship started still ranks as the most nervous of my life. I’m not sure how I slept at all that night, but somehow I did and arrived at the Portland Veterans Affairs Hospital the following morning to start my new career.

And then … nothing happened. Early on that first day, the electronic medical records crashed, and no patients were admitted during our time on “short call.” My upper level resident took care of the one or two established patients on the team (both discharged), so I ended the day with records that would not be broken during the remainder of my residency: 0 notes written, 0 patients seen. Perhaps the most successful first day that any intern, anywhere has ever had, although it prepared me quite poorly for all the subsequent days.

Since I had some time on my hands, I made the 20-minute walk to one of my new hometown’s record stores where Fountains of Wayne (FOW) was playing an acoustic in-store set. Their album from a few years prior, “Welcome Interstate Managers,” was in heavy rotation when I made the drive from Dallas to Portland. It was (and is) a great album for long drives – melodic, catchy, and (mostly) up-tempo. Adam and the band’s singer, Chris Collingwood, played several songs that night on the store’s stage. Then they headed out to the next city, and I headed back home and on to many far-busier days of residency.

We would cross paths again a decade later. I moved back to Texas and became a hospitalist. It turns out that, if you have enough hospitalists of a certain age and if enough of those hospitalists have unearned confidence in their musical ability, then a covers band will undoubtedly be formed. And so, it happened here in San Antonio. We were not selective in our song choices – we played songs from every decade of the last 50 years, bands as popular as the Beatles and as indie as the Rentals. And we played some FOW.

Our band (which will go nameless here so that our YouTube recordings are more difficult to find) played a grand total of one gig during our years of intermittent practicing. That one gig was my wedding rehearsal dinner and the penultimate song we played was “Stacy’s Mom,” which is notable for being both FOW’s biggest hit and a completely inappropriate song to play at a wedding rehearsal dinner. The crowd was probably around the same size as the one that had seen Adam and Chris play in Portland 10 years prior. I don’t think the applause we received was quite as genuine or deserved, though.

After Adam and Chris played their gig, there was an autograph session and I took home a signed poster. Last year, I decided to take it out of storage and hang it in my office. The date of the show and the first day of my physician career, a date now nearly 15 years ago, is written in psychedelic typography at the bottom. The store that I went to that day is no longer there, a victim of progress like so many other record stores across the country. Another location of the same store is still open in Portland. I hope that it and all the other small book and music stores across the country can survive this current crisis, but I know that many will not.

So, here’s to you Adam, and to all the others who have lost their lives to this terrible illness. As a small token of remembrance, I’ll be playing some Fountains of Wayne on the drive home tonight. It’s not quite the same as playing it on a cross-country drive, but hopefully, we will all be able to do that again soon.

Dr. Sehgal is a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System and UT-Health San Antonio. He is a member of the editorial advisory board for The Hospitalist.

Like many in the health care field, I have found it hard to watch the news over these past couple of months when it seems that almost every story is about COVID-19 or its repercussions. Luckily, I have two young daughters who “encourage” me to listen to the Frozen 2 soundtrack instead of putting on the evening news when I get home from work. Still, news manages to seep through my defenses. As I scrolled through some headlines recently, I learned of the death of musician Adam Schlesinger from COVID-19. He wasn’t a household name, but his death still hit me in unexpected ways.

I started internship in late June 2005, in a city (Portland, Ore.) about as different from my previous home (Dallas) as any two places can possibly be. I think the day before internship started still ranks as the most nervous of my life. I’m not sure how I slept at all that night, but somehow I did and arrived at the Portland Veterans Affairs Hospital the following morning to start my new career.

And then … nothing happened. Early on that first day, the electronic medical records crashed, and no patients were admitted during our time on “short call.” My upper level resident took care of the one or two established patients on the team (both discharged), so I ended the day with records that would not be broken during the remainder of my residency: 0 notes written, 0 patients seen. Perhaps the most successful first day that any intern, anywhere has ever had, although it prepared me quite poorly for all the subsequent days.

Since I had some time on my hands, I made the 20-minute walk to one of my new hometown’s record stores where Fountains of Wayne (FOW) was playing an acoustic in-store set. Their album from a few years prior, “Welcome Interstate Managers,” was in heavy rotation when I made the drive from Dallas to Portland. It was (and is) a great album for long drives – melodic, catchy, and (mostly) up-tempo. Adam and the band’s singer, Chris Collingwood, played several songs that night on the store’s stage. Then they headed out to the next city, and I headed back home and on to many far-busier days of residency.

We would cross paths again a decade later. I moved back to Texas and became a hospitalist. It turns out that, if you have enough hospitalists of a certain age and if enough of those hospitalists have unearned confidence in their musical ability, then a covers band will undoubtedly be formed. And so, it happened here in San Antonio. We were not selective in our song choices – we played songs from every decade of the last 50 years, bands as popular as the Beatles and as indie as the Rentals. And we played some FOW.

Our band (which will go nameless here so that our YouTube recordings are more difficult to find) played a grand total of one gig during our years of intermittent practicing. That one gig was my wedding rehearsal dinner and the penultimate song we played was “Stacy’s Mom,” which is notable for being both FOW’s biggest hit and a completely inappropriate song to play at a wedding rehearsal dinner. The crowd was probably around the same size as the one that had seen Adam and Chris play in Portland 10 years prior. I don’t think the applause we received was quite as genuine or deserved, though.

After Adam and Chris played their gig, there was an autograph session and I took home a signed poster. Last year, I decided to take it out of storage and hang it in my office. The date of the show and the first day of my physician career, a date now nearly 15 years ago, is written in psychedelic typography at the bottom. The store that I went to that day is no longer there, a victim of progress like so many other record stores across the country. Another location of the same store is still open in Portland. I hope that it and all the other small book and music stores across the country can survive this current crisis, but I know that many will not.

So, here’s to you Adam, and to all the others who have lost their lives to this terrible illness. As a small token of remembrance, I’ll be playing some Fountains of Wayne on the drive home tonight. It’s not quite the same as playing it on a cross-country drive, but hopefully, we will all be able to do that again soon.

Dr. Sehgal is a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System and UT-Health San Antonio. He is a member of the editorial advisory board for The Hospitalist.

Delivering a goodbye monologue to an elderly patient, I said: “Tomorrow, my colleague Dr. XYZ, who is an excellent physician, will be here in my place, and I will leave a detailed sign out for them.” I was on the last day of a 7-day-long block on hospital medicine service. Typically, when I say goodbye, some patients respond “thank you, enjoy your time,” some don’t care, and some show disappointment at the transition. This patient became uneasy, choking back tears, and said: “But, I don’t want a new doctor. You know me well. ... They don’t even allow my family in the hospital.”

That expression of anxiety, of having to build rapport with a new provider, concerns about continuity of care, and missing support of family members were not alien to me. As I instinctively took a step toward him to offer a comforting hug, an unsolicited voice in my head said, “social distancing.” I steered back, handing him a box of tissues. I continued: “You have come a long way, and things are looking good from here,” providing more details before I left the room. There was a change in my practice that week. I didn’t shake hands with my patients; I didn’t sit on any unassigned chair; I had no family members in the room asking me questions or supporting my patients. I was trying to show empathy or a smile behind a mask and protective eyewear. The business card with photograph had become more critical than ever for patients to “see” their doctor.

Moving from room to room and examining patients, it felt like the coronavirus was changing the practice of medicine beyond concerns of virus transmission, losing a patient, or putting in extra hours. I realized I was missing so-called “nonverbal communication” amid social distancing: facial expressions, social touch, and the support of family or friends to motivate or destress patients. With no visitors and curbed health care staff entries into patient’s rooms, social distancing was amounting to social isolation. My protective gear and social distancing seemed to be reducing my perceived empathy with patients, and the ability to build a good patient-physician relationship.

Amid alarms, beeps, and buzzes, patients were not only missing their families but also the familiar faces of their physicians. I needed to raise my game while embracing the “new normal” of health care. Cut to the next 13 patients: I paid more attention to voice, tone, and posture. I called patient families from the bedside instead of the office. I translated my emotions with words, loud and clear, replacing “your renal function looks better” (said without a smile) with “I am happy to see your renal function better.”

Through years of practice, I felt prepared to deal with feelings of denial, grief, anxiety, and much more, but the emotions arising as a result of this pandemic were unique. “I knew my mother was old, and this day would come,” said one of the inconsolable family members of a critically ill patient. “However, I wished to be at her side that day, not like this.” I spend my days listening to patient and family concerns about unemployment with quarantine, fears of spreading the disease to loved ones, and the possibility of medications not working.

After a long day, I went back to that first elderly patient to see if he was comfortable with the transition of care. I did a video conference with his daughter, and repeated my goodbyes. The patient smiled and said: “Doc, you deserve a break.” That day I learned about the challenges of good clinical rounding in coronavirus times, and how to overcome them. For “millennial” physicians, it is our first pandemic, and we are learning from it every day.

Driving home through empty streets, I concluded that my answers to the clinical questions asked by patients and families lean heavily on ever-changing data, and the treatments offered have yet to prove their mettle. As a result, I will continue to focus as much on the time-tested fundamentals of clinical practice: communication and empathy. I cannot allow the social distancing and the mask to hide my compassion, or take away from patient satisfaction. Shifting gears, I turned on my car radio, using music to reset my mind before attending to my now-homeschooling kids.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Wong CK et al. Effect of facemasks on empathy and relational continuity: A randomised controlled trial in primary care. BMC Fam Pract. 2013;14:200.

2. Little P et al. Randomised controlled trial of a brief intervention targeting predominantly nonverbal communication in general practice consultations. Br J Gen Pract. 2015;65(635):e351-6.

3. Varghese A. A doctor’s touch. TEDGlobal 2011. 2011 Jul. https://www.ted.com/talks/abraham_verghese_a_doctor_s_touch?language=en

Delivering a goodbye monologue to an elderly patient, I said: “Tomorrow, my colleague Dr. XYZ, who is an excellent physician, will be here in my place, and I will leave a detailed sign out for them.” I was on the last day of a 7-day-long block on hospital medicine service. Typically, when I say goodbye, some patients respond “thank you, enjoy your time,” some don’t care, and some show disappointment at the transition. This patient became uneasy, choking back tears, and said: “But, I don’t want a new doctor. You know me well. ... They don’t even allow my family in the hospital.”

That expression of anxiety, of having to build rapport with a new provider, concerns about continuity of care, and missing support of family members were not alien to me. As I instinctively took a step toward him to offer a comforting hug, an unsolicited voice in my head said, “social distancing.” I steered back, handing him a box of tissues. I continued: “You have come a long way, and things are looking good from here,” providing more details before I left the room. There was a change in my practice that week. I didn’t shake hands with my patients; I didn’t sit on any unassigned chair; I had no family members in the room asking me questions or supporting my patients. I was trying to show empathy or a smile behind a mask and protective eyewear. The business card with photograph had become more critical than ever for patients to “see” their doctor.

Moving from room to room and examining patients, it felt like the coronavirus was changing the practice of medicine beyond concerns of virus transmission, losing a patient, or putting in extra hours. I realized I was missing so-called “nonverbal communication” amid social distancing: facial expressions, social touch, and the support of family or friends to motivate or destress patients. With no visitors and curbed health care staff entries into patient’s rooms, social distancing was amounting to social isolation. My protective gear and social distancing seemed to be reducing my perceived empathy with patients, and the ability to build a good patient-physician relationship.

Amid alarms, beeps, and buzzes, patients were not only missing their families but also the familiar faces of their physicians. I needed to raise my game while embracing the “new normal” of health care. Cut to the next 13 patients: I paid more attention to voice, tone, and posture. I called patient families from the bedside instead of the office. I translated my emotions with words, loud and clear, replacing “your renal function looks better” (said without a smile) with “I am happy to see your renal function better.”

Through years of practice, I felt prepared to deal with feelings of denial, grief, anxiety, and much more, but the emotions arising as a result of this pandemic were unique. “I knew my mother was old, and this day would come,” said one of the inconsolable family members of a critically ill patient. “However, I wished to be at her side that day, not like this.” I spend my days listening to patient and family concerns about unemployment with quarantine, fears of spreading the disease to loved ones, and the possibility of medications not working.

After a long day, I went back to that first elderly patient to see if he was comfortable with the transition of care. I did a video conference with his daughter, and repeated my goodbyes. The patient smiled and said: “Doc, you deserve a break.” That day I learned about the challenges of good clinical rounding in coronavirus times, and how to overcome them. For “millennial” physicians, it is our first pandemic, and we are learning from it every day.

Driving home through empty streets, I concluded that my answers to the clinical questions asked by patients and families lean heavily on ever-changing data, and the treatments offered have yet to prove their mettle. As a result, I will continue to focus as much on the time-tested fundamentals of clinical practice: communication and empathy. I cannot allow the social distancing and the mask to hide my compassion, or take away from patient satisfaction. Shifting gears, I turned on my car radio, using music to reset my mind before attending to my now-homeschooling kids.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Wong CK et al. Effect of facemasks on empathy and relational continuity: A randomised controlled trial in primary care. BMC Fam Pract. 2013;14:200.

2. Little P et al. Randomised controlled trial of a brief intervention targeting predominantly nonverbal communication in general practice consultations. Br J Gen Pract. 2015;65(635):e351-6.

3. Varghese A. A doctor’s touch. TEDGlobal 2011. 2011 Jul. https://www.ted.com/talks/abraham_verghese_a_doctor_s_touch?language=en

Delivering a goodbye monologue to an elderly patient, I said: “Tomorrow, my colleague Dr. XYZ, who is an excellent physician, will be here in my place, and I will leave a detailed sign out for them.” I was on the last day of a 7-day-long block on hospital medicine service. Typically, when I say goodbye, some patients respond “thank you, enjoy your time,” some don’t care, and some show disappointment at the transition. This patient became uneasy, choking back tears, and said: “But, I don’t want a new doctor. You know me well. ... They don’t even allow my family in the hospital.”

That expression of anxiety, of having to build rapport with a new provider, concerns about continuity of care, and missing support of family members were not alien to me. As I instinctively took a step toward him to offer a comforting hug, an unsolicited voice in my head said, “social distancing.” I steered back, handing him a box of tissues. I continued: “You have come a long way, and things are looking good from here,” providing more details before I left the room. There was a change in my practice that week. I didn’t shake hands with my patients; I didn’t sit on any unassigned chair; I had no family members in the room asking me questions or supporting my patients. I was trying to show empathy or a smile behind a mask and protective eyewear. The business card with photograph had become more critical than ever for patients to “see” their doctor.

Moving from room to room and examining patients, it felt like the coronavirus was changing the practice of medicine beyond concerns of virus transmission, losing a patient, or putting in extra hours. I realized I was missing so-called “nonverbal communication” amid social distancing: facial expressions, social touch, and the support of family or friends to motivate or destress patients. With no visitors and curbed health care staff entries into patient’s rooms, social distancing was amounting to social isolation. My protective gear and social distancing seemed to be reducing my perceived empathy with patients, and the ability to build a good patient-physician relationship.

Amid alarms, beeps, and buzzes, patients were not only missing their families but also the familiar faces of their physicians. I needed to raise my game while embracing the “new normal” of health care. Cut to the next 13 patients: I paid more attention to voice, tone, and posture. I called patient families from the bedside instead of the office. I translated my emotions with words, loud and clear, replacing “your renal function looks better” (said without a smile) with “I am happy to see your renal function better.”

Through years of practice, I felt prepared to deal with feelings of denial, grief, anxiety, and much more, but the emotions arising as a result of this pandemic were unique. “I knew my mother was old, and this day would come,” said one of the inconsolable family members of a critically ill patient. “However, I wished to be at her side that day, not like this.” I spend my days listening to patient and family concerns about unemployment with quarantine, fears of spreading the disease to loved ones, and the possibility of medications not working.

After a long day, I went back to that first elderly patient to see if he was comfortable with the transition of care. I did a video conference with his daughter, and repeated my goodbyes. The patient smiled and said: “Doc, you deserve a break.” That day I learned about the challenges of good clinical rounding in coronavirus times, and how to overcome them. For “millennial” physicians, it is our first pandemic, and we are learning from it every day.

Driving home through empty streets, I concluded that my answers to the clinical questions asked by patients and families lean heavily on ever-changing data, and the treatments offered have yet to prove their mettle. As a result, I will continue to focus as much on the time-tested fundamentals of clinical practice: communication and empathy. I cannot allow the social distancing and the mask to hide my compassion, or take away from patient satisfaction. Shifting gears, I turned on my car radio, using music to reset my mind before attending to my now-homeschooling kids.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Wong CK et al. Effect of facemasks on empathy and relational continuity: A randomised controlled trial in primary care. BMC Fam Pract. 2013;14:200.

2. Little P et al. Randomised controlled trial of a brief intervention targeting predominantly nonverbal communication in general practice consultations. Br J Gen Pract. 2015;65(635):e351-6.

3. Varghese A. A doctor’s touch. TEDGlobal 2011. 2011 Jul. https://www.ted.com/talks/abraham_verghese_a_doctor_s_touch?language=en

Two case reports published simultaneously in JAMA Dermatology prompted an accompanying editorial calling for dermatologists to actively participate in the characterization and management of skin complications associated with COVID-19 infection.

It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.

“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.

So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.

In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.

In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.

It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.

In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.

Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.

To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.

It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.

The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”

The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”

NYU Langone Health

“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”

While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.

In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.

“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.

One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.

Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.

One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.

Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.

“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.

These are exactly the types of issues being actively investigated at her center.

Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
 

SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.

Two case reports published simultaneously in JAMA Dermatology prompted an accompanying editorial calling for dermatologists to actively participate in the characterization and management of skin complications associated with COVID-19 infection.

It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.

“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.

So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.

In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.

In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.

It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.

In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.

Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.

To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.

It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.

The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”

The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”

NYU Langone Health

“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”

While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.

In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.

“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.

One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.

Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.

One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.

Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.

“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.

These are exactly the types of issues being actively investigated at her center.

Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
 

SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.

Two case reports published simultaneously in JAMA Dermatology prompted an accompanying editorial calling for dermatologists to actively participate in the characterization and management of skin complications associated with COVID-19 infection.

It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.

“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.

So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.

In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.

In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.

It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.

In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.

Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.

To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.

It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.

The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”

The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”

NYU Langone Health

“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”

While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.

In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.

“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.

One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.

Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.

One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.

Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.

“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.

These are exactly the types of issues being actively investigated at her center.

Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
 

SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.

Diastolic dysfunction, a common and often undiagnosed condition in older individuals, could be contributing to the increasing burden of cognitive decline, a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.

“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.

“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.

This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.

Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.

“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.

“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.

Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.

The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.

Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).

An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.

Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).

Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).

The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.

The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.

Earlier interventions

Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”

Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”

Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.

Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.

“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.

With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.

About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.

Dr. Parker has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Diastolic dysfunction, a common and often undiagnosed condition in older individuals, could be contributing to the increasing burden of cognitive decline, a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.

“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.

“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.

This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.

Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.

“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.

“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.

Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.

The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.

Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).

An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.

Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).

Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).

The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.

The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.

Earlier interventions

Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”

Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”

Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.

Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.

“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.

With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.

About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.

Dr. Parker has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Diastolic dysfunction, a common and often undiagnosed condition in older individuals, could be contributing to the increasing burden of cognitive decline, a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.

“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.

“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.

This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.

Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.

“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.

“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.

Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.

The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.

Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).

An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.

Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).

Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).

The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.

The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.

Earlier interventions

Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”

Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”

Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.

Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.

“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.

With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.

About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.

Dr. Parker has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.