Ob.Gyn. News

Do you want to know what keeps us up at night? As 4th-year medical students born, raised, and living in Haiti, we worry about the impact of COVID-19 on our patients.

The pandemic has shaken the world, and Haiti is no exception.

Courtesy Schneider Dorcela

It has taken several months for the disease to spread, and it began with two confirmed cases, one from France and the other from Belgium, on March 19.¹ Much of the spread of COVID-19 in Haiti has been tied to workers returning from the Dominican Republic. As of June 29, Haiti had 5,975 confirmed cases and 105 deaths.² Of course, those numbers sound minuscule, compared with those in the United States, where the number of deaths from COVID-19 surpassed 100,000 several weeks ago. But the population of Haiti is 30 times smaller than that of the United States, and Haiti is the poorest country in the Western Hemisphere. We have watched in horror as the virus has ravaged marginalized groups in the United States and worry that it will do the same in our own country.

Just as the Haitian Ministry of Health worked with various groups to reach the 1-year free of cholera mark in Haiti, groups such as Doctors Without Borders must mobilize to rein in COVID-19.
 

Community transmission rapid

After the first two cases were confirmed, a state of health emergency was immediately declared. Haitian President Jovenel Moïse and other government officials called for the implementation of several measures aimed at limiting the spread of COVID-19.

Schools, universities, clinical training programs, vocational centers, factories, airports, and ports, except for the transport of goods, were all ordered to close until further notice. Gatherings of larger than 10 people were banned. A curfew from 8 p.m. EST time to 5 a.m. EST was imposed. Measures such as those encouraged by U.S. Centers for Disease Control and Prevention, such as hand washing, physical distancing, and staying at home were also encouraged by the Haitian Ministry of Health. Mask wearing in public places was deemed mandatory.

The latest testing data show that community spread has been occurring among the Haitian population at a rapid rate. According to Jean William Pape, MD, Haiti’s top infectious diseases expert and founder of GHESKIO, an iconic infectious disease center that cares for people with HIV-AIDS and tuberculosis, a COVID-19 simulation from Cornell University in New York shows that about 35% of the Haitian population will be infected by the end of August 2020. A simulation by the University of Oxford (England) paints an even more dire picture. That simulation shows that 86% of the population could be infected, More than 9,000 additional hospital beds would be needed, and 20,000 people would be likely to die from COVID-19, Dr. Pape said in an interview with Haiti’s Nouvelliste newspaper.³
 

Medical response

We know that there is a global shortage of health care workers^,4 and Haiti is no exception. According to a 2018 report from the Haitian Ministry of Health, the country has 11,775 health care professionals, including about 3,354 medical doctors, to care for more than 11 million people. That translates to about 23.4 physicians per 100,000.⁵

The pandemic has led some members of this already anemic health care workforce to stay home because of a lack of personal protective equipment. Others, because of reduced hospital or clinic budgets, have been furloughed, making the COVID-19 national health emergency even harder to manage. The rationing of electricity and limited access to clean water⁶ in some areas are other complications that undermine our ability to provide quality care.

But a severe health care shortage is not the only challenge facing Haiti. It spends about $131 U.S. per capita, which makes Haiti one of most vulnerable among low- and middle-income countries in the world. As a poor country,⁷ its health care infrastructure is among the most inadequate and weakest. Prior to COVID-19, medical advocacy groups already had started movements and strikes demanding that the government improve the health care system. The country’s precarious health care infrastructure includes a lack of hospital beds, and basic medical supplies and equipment, such as oxygen and ventilators.⁸ The emergence of COVID-19 has only exacerbated the situation.

Clinical training programs have been suspended, many doctors and nurses are on quarantine, and some hospitals and clinics are closing. We have witnessed makeshift voodoo clinics built by Haitian voodoo leaders to receive, hospitalize, and treat COVID-19 patients through rituals and herbal remedies. In some areas of the country, residents have protested against the opening of several COVID-19 treatment and management centers.
 

Unique cultural challenges

Public health officials around the world are facing challenges persuading citizens to engage in behaviors that could protect them from the virus.

Just as in America, where many people opt to not wear face coverings^9,10 despite the public health risks, deep distrust of the Haitian government has undermined the messages of President Moïse and public healthofficials about the role of masks in limiting the spread of COVID.We see large numbers of unmasked people on the streets in the informal markets every day. Crammed tap-taps and overloaded motorcycles are moving everywhere. This also could be tied to cultural attitudes about COVID that persist among some Haitians.For example, many people with signs and symptoms of COVID-19 are afraid of going to the hospital to get tested and receive care, and resort to going to the voodoo clinics. Along with rituals, voodoo priests have been serving up teas with ingredients, including moringa, eucalyptus, ginger, and honey to those seeking COVID-19 care in the centers. The voodoo priests claim that the teas they serve strengthen the immune system.

In addition, it is difficult for poor people who live in small quarters with several other people to adhere to physical distancing.¹¹
 

Stigma and violence

Other barriers in the fight against COVID-19 in Haiti are stigma and violence. If widespread testing were available, some Haitians would opt not to do so – despite clear signs and symptoms of the infection. Some people who would get tested if they could are afraid to do so because of fears tied to being attacked by neighbors.

When Haitian University professor Bellamy Nelson and his girlfriend returned to Haiti from the United States in March and began experiencing some pain and fever, he experienced attacks from neighbors, he said in an interview. He said neighbors threatened to burn down his house. When an ambulance arrived at his house to transport him to a hospital, it had to drive through back roads to avoid people armed with rocks, fire, and machetes, he told us. No hospital wanted to admit him. Eventually, Professor Nelson self-quarantined at home, he said.

In another incident, a national ambulance center in Gonaïves, a town toward the northern region of Haiti, reportedly was vandalized, because COVID-19 equipment and supplies used to treat people had been stored there. Hospital Bernard Mevs, along with many other hospitals, was forced by the area’s residents to suspend the plan to open a center for COVID-19 management. Threats to burn down the hospitals caused the leaders of the hospitals to back down and give up a plan to build a 20-bed COVID-19 response center.
 

Maternal health

Another concern we have about the pandemic is the risk it could be to pregnant women. On average, 94,000 deaths occur annually in Haiti. Out of this number, maternal mortality accounts for 1,000. In 2017, for every 100,000 live births for women of reproductive age from 15 to 49 years old, 480 women died. In contrast, in the Dominican Republic, 95 women died per 100,000 that same year. In the United States, 19 died, and in Norway, no more than 2 died that year.¹²

Some of the primary factors contributing to the crisis are limited accessibility, inadequate health care facilities, and an inadequate number of trained health care practitioners; low percentages of skilled attendants at deliveries and of prenatal and postnatal visits; and high numbers of high-risk deliveries in nonqualified health facilities.

During the COVID-19 national health emergency, with most hospitals reducing their health care personnel either because of budget-related reasons or because they are on quarantine, this maternal-fetal health crisis has escalated.

One of the biggest hospitals in Jacmel, a town in the southern region of Haiti, has stopped its prenatal care program. In Delmas, the city with the highest incidence and prevalence of COVID-19, Hôpital Universitaire de la Paix has reduced this program to 50% of its capacity and gynecologic care has been completely suspended. Hôpital St. Luc, one of the first hospitals in the western region of Haiti to open its doors to care for COVID-19 patients, has recently shut down the entire maternal-fetal department.

So, access to prenatal and postnatal care, including the ability to deliver babies in health care institutions, is significantly reduced because of COVID-19. This leaves thousands of already vulnerable pregnant women at risk and having to deliver domestically with little to no health care professional assistance. We worry that, in light of the data, more women and babies will die because of the COVID-19 pandemic.
 

A call to action

Despite these conditions, there are reasons for hope. Various groups, both from the international community and locally have mobilized to respond to the pandemic.

International health care organizations such as Doctors Without Borders and Partners in Health, and local groups such as GHESKIO, the St. Luke Foundation for Haiti, and others have been collaborating with the Haitian Ministry of Health to devise and strategic plans and deploy valuable resources with the common goal of saving lives from COVID-19.

GHESKIO, for example, under Dr. Pape’s leadership, currently has one of the three COVID-19 testing centers in the country. It also has two COVID-19 treatment centers in full operation, in Port-au-Prince, the capital city, managing and treating 520 patients with confirmed COVID-19. GHESKIO, which has been in the front lines of previous major infectious disease outbreaks,¹³ has trained about 200 clinicians from both public and private health care institutions to care for COVID-19 patients.

Doctors Without Borders has been investing in efforts to support the Ministry of Health by converting and renovating its Burn Center in Drouillard, a small section of the city of Cité Soleil, one of the country’s biggest slums. In May, as part of its COVID-19 response, it launched a 20-bed capacity center that can accommodate up to 45 beds to care for patients who have tested positive for COVID-19.

Partners in Health, the Boston-based nonprofit health care organization cofounded in 1987 by American anthropologist and infectious disease specialist, Paul Farmer, MD, and the largest nonprofit health care provider in Haiti, also joined the Ministry of Health through its national and public health efforts to tackle COVID-19 in Haiti. Partners in Health, through its sister organization, Zanmi Lasante, has pioneered the movement of diagnosing and treating people with HIV-AIDS and TB. Since the late 1990s, its efforts against both infectious diseases have helped 15,000 HIV-positive patients begin and remain on treatment. And every year, 1,500 TB patients have started treatment on the path to a cure.

Early in the pandemic in Haiti, Partners in Health, through its state-of-the-art 300-bed university hospital (Hôpital Universitaire de Mirebalais de Mirebalais), was the first to open a COVID-19 center with a 20-bed capacity and has been caring for COVID-19 patients since then. In June, Partners in Health supported and inaugurated the renovation of the internal medicine department at one of its affiliated community hospitals, Hôpital Saint-Nicolas de Saint Marc. That department will have a 24-bed capacity that can extend up to 36 beds to manage and treat COVID-19 patients.

In total, currently, 26 COVID-19 centers with a capacity of 1,011 beds are available to serve, manage, and treat Haitian patients affected with COVID-19. But are those efforts enough? No.

Haiti, as a weak state even before COVID-19, continues to need funding from the international community so it can strengthen its health care infrastructure to be effective and strong in fighting against COVID-19.

In addition, we would like to see preventive initiatives implemented on the local level. Our family has taken on a role that, we think, could help conquer COVID-19 if others followed suit on a large scale.

As part of our contribution in tackling COVID-19, the two of us have launched a small-scale community experiment. We have educated our family in Delmas about COVID-19 and subsequently launched an awareness campaign in the community. We dispatched small groups that go door to door in the community to educate neighbors about the disease in an effort to help them understand that COVID-19 is real and it is normal for people that feel they may have the disease to seek medical care. This approach helps suppress the transmission of the virus. This pilot project could be reproduced in several other communities. It is easy to operate, rapid, effective, and cost-free. The community has been very receptive to and grateful for our efforts.

Like other countries across the world, Haiti was not ready for COVID-19. But we are confident that, with help from the international community, organizations such as GHESKIO,¹⁴ and with due diligence on the local level, we are strong and resilient enough to beat COVID. We must act together – quickly.

 

References

1. Sénat JD. Coronavirus: 2 cas confirmés en Haïti, Jovenel Moïse décrète l’état d’ur-gence sanitaire. 2020 Le Nouvelliste.

2. Haitian Ministry of Health.

3. “Entre appel a la solidarite et de sombres previsions, le Dr William Pape fait le point.” Le Nouvelliste.

4. Darzi A and Evans T. Lancet. 2016 Nov-Dec 26. 388;10060:2576-7.

5. Rapport Statistique 2018. 2019 Republic of Haiti.

6. Sentlinger K. “Water Crisis in Haiti.” The Water Project.

7. The World Bank in Haiti. worldbank.org.

8. Cenat JM. Travel Med Infect Dis. 2020 Mar 28. doi: 10.1016/jtmaid.2020.101684.

9. Block D. “Why some Americans resist wearing face masks.” voanews.com. 2020 May 31.

10. Panceski B and Douglas J. “Masks could help stop coronavirus. So why are they still controversial?” wsj.com. Updated 29 Jun 2020.

11. Bojarski S. “Social distancing: A luxury Haiti’s poor cannot afford. The Haitian Times. 2020 Apr.

12. World Health Organization, UNICEF, World Bank Group, and the U.N. Population Division. Maternal mortality ratio, Haiti.

13. Feliciano I and Kargbo C. “As COVID cases surge, Haiti’s Dr. Pape is on the front line again.” PBS NewsHour Weekend. 2020 Jun 13.

14. Liautaud B and Deschamps MM. New Engl J Med. 2020 Jun 16.
 

Mr. Dorcela is a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince, Haiti. He also is a medical intern at Unité de Médecine Familiale Hôpital Saint Nicolas in Saint-Marc. Mr. Dorcela has no disclosures. Mr. St. Jean, who is Mr. Dorcela’s brother, is also a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince. He has no disclosures.

Do you want to know what keeps us up at night? As 4th-year medical students born, raised, and living in Haiti, we worry about the impact of COVID-19 on our patients.

The pandemic has shaken the world, and Haiti is no exception.

Courtesy Schneider Dorcela

It has taken several months for the disease to spread, and it began with two confirmed cases, one from France and the other from Belgium, on March 19.¹ Much of the spread of COVID-19 in Haiti has been tied to workers returning from the Dominican Republic. As of June 29, Haiti had 5,975 confirmed cases and 105 deaths.² Of course, those numbers sound minuscule, compared with those in the United States, where the number of deaths from COVID-19 surpassed 100,000 several weeks ago. But the population of Haiti is 30 times smaller than that of the United States, and Haiti is the poorest country in the Western Hemisphere. We have watched in horror as the virus has ravaged marginalized groups in the United States and worry that it will do the same in our own country.

Just as the Haitian Ministry of Health worked with various groups to reach the 1-year free of cholera mark in Haiti, groups such as Doctors Without Borders must mobilize to rein in COVID-19.
 

Community transmission rapid

After the first two cases were confirmed, a state of health emergency was immediately declared. Haitian President Jovenel Moïse and other government officials called for the implementation of several measures aimed at limiting the spread of COVID-19.

Schools, universities, clinical training programs, vocational centers, factories, airports, and ports, except for the transport of goods, were all ordered to close until further notice. Gatherings of larger than 10 people were banned. A curfew from 8 p.m. EST time to 5 a.m. EST was imposed. Measures such as those encouraged by U.S. Centers for Disease Control and Prevention, such as hand washing, physical distancing, and staying at home were also encouraged by the Haitian Ministry of Health. Mask wearing in public places was deemed mandatory.

The latest testing data show that community spread has been occurring among the Haitian population at a rapid rate. According to Jean William Pape, MD, Haiti’s top infectious diseases expert and founder of GHESKIO, an iconic infectious disease center that cares for people with HIV-AIDS and tuberculosis, a COVID-19 simulation from Cornell University in New York shows that about 35% of the Haitian population will be infected by the end of August 2020. A simulation by the University of Oxford (England) paints an even more dire picture. That simulation shows that 86% of the population could be infected, More than 9,000 additional hospital beds would be needed, and 20,000 people would be likely to die from COVID-19, Dr. Pape said in an interview with Haiti’s Nouvelliste newspaper.³
 

Medical response

We know that there is a global shortage of health care workers^,4 and Haiti is no exception. According to a 2018 report from the Haitian Ministry of Health, the country has 11,775 health care professionals, including about 3,354 medical doctors, to care for more than 11 million people. That translates to about 23.4 physicians per 100,000.⁵

The pandemic has led some members of this already anemic health care workforce to stay home because of a lack of personal protective equipment. Others, because of reduced hospital or clinic budgets, have been furloughed, making the COVID-19 national health emergency even harder to manage. The rationing of electricity and limited access to clean water⁶ in some areas are other complications that undermine our ability to provide quality care.

But a severe health care shortage is not the only challenge facing Haiti. It spends about $131 U.S. per capita, which makes Haiti one of most vulnerable among low- and middle-income countries in the world. As a poor country,⁷ its health care infrastructure is among the most inadequate and weakest. Prior to COVID-19, medical advocacy groups already had started movements and strikes demanding that the government improve the health care system. The country’s precarious health care infrastructure includes a lack of hospital beds, and basic medical supplies and equipment, such as oxygen and ventilators.⁸ The emergence of COVID-19 has only exacerbated the situation.

Clinical training programs have been suspended, many doctors and nurses are on quarantine, and some hospitals and clinics are closing. We have witnessed makeshift voodoo clinics built by Haitian voodoo leaders to receive, hospitalize, and treat COVID-19 patients through rituals and herbal remedies. In some areas of the country, residents have protested against the opening of several COVID-19 treatment and management centers.
 

Unique cultural challenges

Public health officials around the world are facing challenges persuading citizens to engage in behaviors that could protect them from the virus.

Just as in America, where many people opt to not wear face coverings^9,10 despite the public health risks, deep distrust of the Haitian government has undermined the messages of President Moïse and public healthofficials about the role of masks in limiting the spread of COVID.We see large numbers of unmasked people on the streets in the informal markets every day. Crammed tap-taps and overloaded motorcycles are moving everywhere. This also could be tied to cultural attitudes about COVID that persist among some Haitians.For example, many people with signs and symptoms of COVID-19 are afraid of going to the hospital to get tested and receive care, and resort to going to the voodoo clinics. Along with rituals, voodoo priests have been serving up teas with ingredients, including moringa, eucalyptus, ginger, and honey to those seeking COVID-19 care in the centers. The voodoo priests claim that the teas they serve strengthen the immune system.

In addition, it is difficult for poor people who live in small quarters with several other people to adhere to physical distancing.¹¹
 

Stigma and violence

Other barriers in the fight against COVID-19 in Haiti are stigma and violence. If widespread testing were available, some Haitians would opt not to do so – despite clear signs and symptoms of the infection. Some people who would get tested if they could are afraid to do so because of fears tied to being attacked by neighbors.

When Haitian University professor Bellamy Nelson and his girlfriend returned to Haiti from the United States in March and began experiencing some pain and fever, he experienced attacks from neighbors, he said in an interview. He said neighbors threatened to burn down his house. When an ambulance arrived at his house to transport him to a hospital, it had to drive through back roads to avoid people armed with rocks, fire, and machetes, he told us. No hospital wanted to admit him. Eventually, Professor Nelson self-quarantined at home, he said.

In another incident, a national ambulance center in Gonaïves, a town toward the northern region of Haiti, reportedly was vandalized, because COVID-19 equipment and supplies used to treat people had been stored there. Hospital Bernard Mevs, along with many other hospitals, was forced by the area’s residents to suspend the plan to open a center for COVID-19 management. Threats to burn down the hospitals caused the leaders of the hospitals to back down and give up a plan to build a 20-bed COVID-19 response center.
 

Maternal health

Another concern we have about the pandemic is the risk it could be to pregnant women. On average, 94,000 deaths occur annually in Haiti. Out of this number, maternal mortality accounts for 1,000. In 2017, for every 100,000 live births for women of reproductive age from 15 to 49 years old, 480 women died. In contrast, in the Dominican Republic, 95 women died per 100,000 that same year. In the United States, 19 died, and in Norway, no more than 2 died that year.¹²

Some of the primary factors contributing to the crisis are limited accessibility, inadequate health care facilities, and an inadequate number of trained health care practitioners; low percentages of skilled attendants at deliveries and of prenatal and postnatal visits; and high numbers of high-risk deliveries in nonqualified health facilities.

During the COVID-19 national health emergency, with most hospitals reducing their health care personnel either because of budget-related reasons or because they are on quarantine, this maternal-fetal health crisis has escalated.

One of the biggest hospitals in Jacmel, a town in the southern region of Haiti, has stopped its prenatal care program. In Delmas, the city with the highest incidence and prevalence of COVID-19, Hôpital Universitaire de la Paix has reduced this program to 50% of its capacity and gynecologic care has been completely suspended. Hôpital St. Luc, one of the first hospitals in the western region of Haiti to open its doors to care for COVID-19 patients, has recently shut down the entire maternal-fetal department.

So, access to prenatal and postnatal care, including the ability to deliver babies in health care institutions, is significantly reduced because of COVID-19. This leaves thousands of already vulnerable pregnant women at risk and having to deliver domestically with little to no health care professional assistance. We worry that, in light of the data, more women and babies will die because of the COVID-19 pandemic.
 

A call to action

Despite these conditions, there are reasons for hope. Various groups, both from the international community and locally have mobilized to respond to the pandemic.

International health care organizations such as Doctors Without Borders and Partners in Health, and local groups such as GHESKIO, the St. Luke Foundation for Haiti, and others have been collaborating with the Haitian Ministry of Health to devise and strategic plans and deploy valuable resources with the common goal of saving lives from COVID-19.

GHESKIO, for example, under Dr. Pape’s leadership, currently has one of the three COVID-19 testing centers in the country. It also has two COVID-19 treatment centers in full operation, in Port-au-Prince, the capital city, managing and treating 520 patients with confirmed COVID-19. GHESKIO, which has been in the front lines of previous major infectious disease outbreaks,¹³ has trained about 200 clinicians from both public and private health care institutions to care for COVID-19 patients.

Doctors Without Borders has been investing in efforts to support the Ministry of Health by converting and renovating its Burn Center in Drouillard, a small section of the city of Cité Soleil, one of the country’s biggest slums. In May, as part of its COVID-19 response, it launched a 20-bed capacity center that can accommodate up to 45 beds to care for patients who have tested positive for COVID-19.

Partners in Health, the Boston-based nonprofit health care organization cofounded in 1987 by American anthropologist and infectious disease specialist, Paul Farmer, MD, and the largest nonprofit health care provider in Haiti, also joined the Ministry of Health through its national and public health efforts to tackle COVID-19 in Haiti. Partners in Health, through its sister organization, Zanmi Lasante, has pioneered the movement of diagnosing and treating people with HIV-AIDS and TB. Since the late 1990s, its efforts against both infectious diseases have helped 15,000 HIV-positive patients begin and remain on treatment. And every year, 1,500 TB patients have started treatment on the path to a cure.

Early in the pandemic in Haiti, Partners in Health, through its state-of-the-art 300-bed university hospital (Hôpital Universitaire de Mirebalais de Mirebalais), was the first to open a COVID-19 center with a 20-bed capacity and has been caring for COVID-19 patients since then. In June, Partners in Health supported and inaugurated the renovation of the internal medicine department at one of its affiliated community hospitals, Hôpital Saint-Nicolas de Saint Marc. That department will have a 24-bed capacity that can extend up to 36 beds to manage and treat COVID-19 patients.

In total, currently, 26 COVID-19 centers with a capacity of 1,011 beds are available to serve, manage, and treat Haitian patients affected with COVID-19. But are those efforts enough? No.

Haiti, as a weak state even before COVID-19, continues to need funding from the international community so it can strengthen its health care infrastructure to be effective and strong in fighting against COVID-19.

In addition, we would like to see preventive initiatives implemented on the local level. Our family has taken on a role that, we think, could help conquer COVID-19 if others followed suit on a large scale.

As part of our contribution in tackling COVID-19, the two of us have launched a small-scale community experiment. We have educated our family in Delmas about COVID-19 and subsequently launched an awareness campaign in the community. We dispatched small groups that go door to door in the community to educate neighbors about the disease in an effort to help them understand that COVID-19 is real and it is normal for people that feel they may have the disease to seek medical care. This approach helps suppress the transmission of the virus. This pilot project could be reproduced in several other communities. It is easy to operate, rapid, effective, and cost-free. The community has been very receptive to and grateful for our efforts.

Like other countries across the world, Haiti was not ready for COVID-19. But we are confident that, with help from the international community, organizations such as GHESKIO,¹⁴ and with due diligence on the local level, we are strong and resilient enough to beat COVID. We must act together – quickly.

 

References

1. Sénat JD. Coronavirus: 2 cas confirmés en Haïti, Jovenel Moïse décrète l’état d’ur-gence sanitaire. 2020 Le Nouvelliste.

2. Haitian Ministry of Health.

3. “Entre appel a la solidarite et de sombres previsions, le Dr William Pape fait le point.” Le Nouvelliste.

4. Darzi A and Evans T. Lancet. 2016 Nov-Dec 26. 388;10060:2576-7.

5. Rapport Statistique 2018. 2019 Republic of Haiti.

6. Sentlinger K. “Water Crisis in Haiti.” The Water Project.

7. The World Bank in Haiti. worldbank.org.

8. Cenat JM. Travel Med Infect Dis. 2020 Mar 28. doi: 10.1016/jtmaid.2020.101684.

9. Block D. “Why some Americans resist wearing face masks.” voanews.com. 2020 May 31.

10. Panceski B and Douglas J. “Masks could help stop coronavirus. So why are they still controversial?” wsj.com. Updated 29 Jun 2020.

11. Bojarski S. “Social distancing: A luxury Haiti’s poor cannot afford. The Haitian Times. 2020 Apr.

12. World Health Organization, UNICEF, World Bank Group, and the U.N. Population Division. Maternal mortality ratio, Haiti.

13. Feliciano I and Kargbo C. “As COVID cases surge, Haiti’s Dr. Pape is on the front line again.” PBS NewsHour Weekend. 2020 Jun 13.

14. Liautaud B and Deschamps MM. New Engl J Med. 2020 Jun 16.
 

Mr. Dorcela is a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince, Haiti. He also is a medical intern at Unité de Médecine Familiale Hôpital Saint Nicolas in Saint-Marc. Mr. Dorcela has no disclosures. Mr. St. Jean, who is Mr. Dorcela’s brother, is also a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince. He has no disclosures.

Do you want to know what keeps us up at night? As 4th-year medical students born, raised, and living in Haiti, we worry about the impact of COVID-19 on our patients.

The pandemic has shaken the world, and Haiti is no exception.

Courtesy Schneider Dorcela

It has taken several months for the disease to spread, and it began with two confirmed cases, one from France and the other from Belgium, on March 19.¹ Much of the spread of COVID-19 in Haiti has been tied to workers returning from the Dominican Republic. As of June 29, Haiti had 5,975 confirmed cases and 105 deaths.² Of course, those numbers sound minuscule, compared with those in the United States, where the number of deaths from COVID-19 surpassed 100,000 several weeks ago. But the population of Haiti is 30 times smaller than that of the United States, and Haiti is the poorest country in the Western Hemisphere. We have watched in horror as the virus has ravaged marginalized groups in the United States and worry that it will do the same in our own country.

Just as the Haitian Ministry of Health worked with various groups to reach the 1-year free of cholera mark in Haiti, groups such as Doctors Without Borders must mobilize to rein in COVID-19.
 

Community transmission rapid

After the first two cases were confirmed, a state of health emergency was immediately declared. Haitian President Jovenel Moïse and other government officials called for the implementation of several measures aimed at limiting the spread of COVID-19.

Schools, universities, clinical training programs, vocational centers, factories, airports, and ports, except for the transport of goods, were all ordered to close until further notice. Gatherings of larger than 10 people were banned. A curfew from 8 p.m. EST time to 5 a.m. EST was imposed. Measures such as those encouraged by U.S. Centers for Disease Control and Prevention, such as hand washing, physical distancing, and staying at home were also encouraged by the Haitian Ministry of Health. Mask wearing in public places was deemed mandatory.

The latest testing data show that community spread has been occurring among the Haitian population at a rapid rate. According to Jean William Pape, MD, Haiti’s top infectious diseases expert and founder of GHESKIO, an iconic infectious disease center that cares for people with HIV-AIDS and tuberculosis, a COVID-19 simulation from Cornell University in New York shows that about 35% of the Haitian population will be infected by the end of August 2020. A simulation by the University of Oxford (England) paints an even more dire picture. That simulation shows that 86% of the population could be infected, More than 9,000 additional hospital beds would be needed, and 20,000 people would be likely to die from COVID-19, Dr. Pape said in an interview with Haiti’s Nouvelliste newspaper.³
 

Medical response

We know that there is a global shortage of health care workers^,4 and Haiti is no exception. According to a 2018 report from the Haitian Ministry of Health, the country has 11,775 health care professionals, including about 3,354 medical doctors, to care for more than 11 million people. That translates to about 23.4 physicians per 100,000.⁵

The pandemic has led some members of this already anemic health care workforce to stay home because of a lack of personal protective equipment. Others, because of reduced hospital or clinic budgets, have been furloughed, making the COVID-19 national health emergency even harder to manage. The rationing of electricity and limited access to clean water⁶ in some areas are other complications that undermine our ability to provide quality care.

But a severe health care shortage is not the only challenge facing Haiti. It spends about $131 U.S. per capita, which makes Haiti one of most vulnerable among low- and middle-income countries in the world. As a poor country,⁷ its health care infrastructure is among the most inadequate and weakest. Prior to COVID-19, medical advocacy groups already had started movements and strikes demanding that the government improve the health care system. The country’s precarious health care infrastructure includes a lack of hospital beds, and basic medical supplies and equipment, such as oxygen and ventilators.⁸ The emergence of COVID-19 has only exacerbated the situation.

Clinical training programs have been suspended, many doctors and nurses are on quarantine, and some hospitals and clinics are closing. We have witnessed makeshift voodoo clinics built by Haitian voodoo leaders to receive, hospitalize, and treat COVID-19 patients through rituals and herbal remedies. In some areas of the country, residents have protested against the opening of several COVID-19 treatment and management centers.
 

Unique cultural challenges

Public health officials around the world are facing challenges persuading citizens to engage in behaviors that could protect them from the virus.

Just as in America, where many people opt to not wear face coverings^9,10 despite the public health risks, deep distrust of the Haitian government has undermined the messages of President Moïse and public healthofficials about the role of masks in limiting the spread of COVID.We see large numbers of unmasked people on the streets in the informal markets every day. Crammed tap-taps and overloaded motorcycles are moving everywhere. This also could be tied to cultural attitudes about COVID that persist among some Haitians.For example, many people with signs and symptoms of COVID-19 are afraid of going to the hospital to get tested and receive care, and resort to going to the voodoo clinics. Along with rituals, voodoo priests have been serving up teas with ingredients, including moringa, eucalyptus, ginger, and honey to those seeking COVID-19 care in the centers. The voodoo priests claim that the teas they serve strengthen the immune system.

In addition, it is difficult for poor people who live in small quarters with several other people to adhere to physical distancing.¹¹
 

Stigma and violence

Other barriers in the fight against COVID-19 in Haiti are stigma and violence. If widespread testing were available, some Haitians would opt not to do so – despite clear signs and symptoms of the infection. Some people who would get tested if they could are afraid to do so because of fears tied to being attacked by neighbors.

When Haitian University professor Bellamy Nelson and his girlfriend returned to Haiti from the United States in March and began experiencing some pain and fever, he experienced attacks from neighbors, he said in an interview. He said neighbors threatened to burn down his house. When an ambulance arrived at his house to transport him to a hospital, it had to drive through back roads to avoid people armed with rocks, fire, and machetes, he told us. No hospital wanted to admit him. Eventually, Professor Nelson self-quarantined at home, he said.

In another incident, a national ambulance center in Gonaïves, a town toward the northern region of Haiti, reportedly was vandalized, because COVID-19 equipment and supplies used to treat people had been stored there. Hospital Bernard Mevs, along with many other hospitals, was forced by the area’s residents to suspend the plan to open a center for COVID-19 management. Threats to burn down the hospitals caused the leaders of the hospitals to back down and give up a plan to build a 20-bed COVID-19 response center.
 

Maternal health

Another concern we have about the pandemic is the risk it could be to pregnant women. On average, 94,000 deaths occur annually in Haiti. Out of this number, maternal mortality accounts for 1,000. In 2017, for every 100,000 live births for women of reproductive age from 15 to 49 years old, 480 women died. In contrast, in the Dominican Republic, 95 women died per 100,000 that same year. In the United States, 19 died, and in Norway, no more than 2 died that year.¹²

Some of the primary factors contributing to the crisis are limited accessibility, inadequate health care facilities, and an inadequate number of trained health care practitioners; low percentages of skilled attendants at deliveries and of prenatal and postnatal visits; and high numbers of high-risk deliveries in nonqualified health facilities.

During the COVID-19 national health emergency, with most hospitals reducing their health care personnel either because of budget-related reasons or because they are on quarantine, this maternal-fetal health crisis has escalated.

One of the biggest hospitals in Jacmel, a town in the southern region of Haiti, has stopped its prenatal care program. In Delmas, the city with the highest incidence and prevalence of COVID-19, Hôpital Universitaire de la Paix has reduced this program to 50% of its capacity and gynecologic care has been completely suspended. Hôpital St. Luc, one of the first hospitals in the western region of Haiti to open its doors to care for COVID-19 patients, has recently shut down the entire maternal-fetal department.

So, access to prenatal and postnatal care, including the ability to deliver babies in health care institutions, is significantly reduced because of COVID-19. This leaves thousands of already vulnerable pregnant women at risk and having to deliver domestically with little to no health care professional assistance. We worry that, in light of the data, more women and babies will die because of the COVID-19 pandemic.
 

A call to action

Despite these conditions, there are reasons for hope. Various groups, both from the international community and locally have mobilized to respond to the pandemic.

International health care organizations such as Doctors Without Borders and Partners in Health, and local groups such as GHESKIO, the St. Luke Foundation for Haiti, and others have been collaborating with the Haitian Ministry of Health to devise and strategic plans and deploy valuable resources with the common goal of saving lives from COVID-19.

GHESKIO, for example, under Dr. Pape’s leadership, currently has one of the three COVID-19 testing centers in the country. It also has two COVID-19 treatment centers in full operation, in Port-au-Prince, the capital city, managing and treating 520 patients with confirmed COVID-19. GHESKIO, which has been in the front lines of previous major infectious disease outbreaks,¹³ has trained about 200 clinicians from both public and private health care institutions to care for COVID-19 patients.

Doctors Without Borders has been investing in efforts to support the Ministry of Health by converting and renovating its Burn Center in Drouillard, a small section of the city of Cité Soleil, one of the country’s biggest slums. In May, as part of its COVID-19 response, it launched a 20-bed capacity center that can accommodate up to 45 beds to care for patients who have tested positive for COVID-19.

Partners in Health, the Boston-based nonprofit health care organization cofounded in 1987 by American anthropologist and infectious disease specialist, Paul Farmer, MD, and the largest nonprofit health care provider in Haiti, also joined the Ministry of Health through its national and public health efforts to tackle COVID-19 in Haiti. Partners in Health, through its sister organization, Zanmi Lasante, has pioneered the movement of diagnosing and treating people with HIV-AIDS and TB. Since the late 1990s, its efforts against both infectious diseases have helped 15,000 HIV-positive patients begin and remain on treatment. And every year, 1,500 TB patients have started treatment on the path to a cure.

Early in the pandemic in Haiti, Partners in Health, through its state-of-the-art 300-bed university hospital (Hôpital Universitaire de Mirebalais de Mirebalais), was the first to open a COVID-19 center with a 20-bed capacity and has been caring for COVID-19 patients since then. In June, Partners in Health supported and inaugurated the renovation of the internal medicine department at one of its affiliated community hospitals, Hôpital Saint-Nicolas de Saint Marc. That department will have a 24-bed capacity that can extend up to 36 beds to manage and treat COVID-19 patients.

In total, currently, 26 COVID-19 centers with a capacity of 1,011 beds are available to serve, manage, and treat Haitian patients affected with COVID-19. But are those efforts enough? No.

Haiti, as a weak state even before COVID-19, continues to need funding from the international community so it can strengthen its health care infrastructure to be effective and strong in fighting against COVID-19.

In addition, we would like to see preventive initiatives implemented on the local level. Our family has taken on a role that, we think, could help conquer COVID-19 if others followed suit on a large scale.

As part of our contribution in tackling COVID-19, the two of us have launched a small-scale community experiment. We have educated our family in Delmas about COVID-19 and subsequently launched an awareness campaign in the community. We dispatched small groups that go door to door in the community to educate neighbors about the disease in an effort to help them understand that COVID-19 is real and it is normal for people that feel they may have the disease to seek medical care. This approach helps suppress the transmission of the virus. This pilot project could be reproduced in several other communities. It is easy to operate, rapid, effective, and cost-free. The community has been very receptive to and grateful for our efforts.

Like other countries across the world, Haiti was not ready for COVID-19. But we are confident that, with help from the international community, organizations such as GHESKIO,¹⁴ and with due diligence on the local level, we are strong and resilient enough to beat COVID. We must act together – quickly.

 

References

1. Sénat JD. Coronavirus: 2 cas confirmés en Haïti, Jovenel Moïse décrète l’état d’ur-gence sanitaire. 2020 Le Nouvelliste.

2. Haitian Ministry of Health.

3. “Entre appel a la solidarite et de sombres previsions, le Dr William Pape fait le point.” Le Nouvelliste.

4. Darzi A and Evans T. Lancet. 2016 Nov-Dec 26. 388;10060:2576-7.

5. Rapport Statistique 2018. 2019 Republic of Haiti.

6. Sentlinger K. “Water Crisis in Haiti.” The Water Project.

7. The World Bank in Haiti. worldbank.org.

8. Cenat JM. Travel Med Infect Dis. 2020 Mar 28. doi: 10.1016/jtmaid.2020.101684.

9. Block D. “Why some Americans resist wearing face masks.” voanews.com. 2020 May 31.

10. Panceski B and Douglas J. “Masks could help stop coronavirus. So why are they still controversial?” wsj.com. Updated 29 Jun 2020.

11. Bojarski S. “Social distancing: A luxury Haiti’s poor cannot afford. The Haitian Times. 2020 Apr.

12. World Health Organization, UNICEF, World Bank Group, and the U.N. Population Division. Maternal mortality ratio, Haiti.

13. Feliciano I and Kargbo C. “As COVID cases surge, Haiti’s Dr. Pape is on the front line again.” PBS NewsHour Weekend. 2020 Jun 13.

14. Liautaud B and Deschamps MM. New Engl J Med. 2020 Jun 16.
 

Mr. Dorcela is a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince, Haiti. He also is a medical intern at Unité de Médecine Familiale Hôpital Saint Nicolas in Saint-Marc. Mr. Dorcela has no disclosures. Mr. St. Jean, who is Mr. Dorcela’s brother, is also a senior medical student at Faculté des Sciences de la Santé Université Quisqueya in Port-au-Prince. He has no disclosures.

Most Americans support the required use of face masks in public, along with universal COVID-19 testing, to provide a safe work environment during the pandemic, according to a new report from the Commonwealth Fund.

Results of a recent survey show that 85% of adults believe that it is very or somewhat important to require everyone to wear a face mask “at work, when shopping, and on public transportation,” said Sara R. Collins, PhD, vice president for health care coverage and access at the fund, and associates.

In that survey, conducted from May 13 to June 2, 2020, and involving 2,271 respondents, regular COVID-19 testing for everyone was supported by 81% of the sample as way to ensure a safe work environment until a vaccine is available, the researchers said in the report.

Support on both issues was consistently high across both racial/ethnic and political lines. Mandatory mask use gained 91% support among black respondents, 90% in Hispanics, and 82% in whites. There was greater distance between the political parties, but 70% of Republicans and Republican-leaning independents support mask use, compared with 95% of Democrats and Democratic-leaning independents, they said.

Regarding regular testing, 66% of Republicans and those leaning Republican said that it was very/somewhat important to ensure a safe work environment, as did 91% on the Democratic side. Hispanics offered the most support by race/ethnicity, with 90% saying that testing was very/somewhat important, compared with 86% of black respondents and 78% of white respondents, Dr. Collins and associates said.

A question on contact tracing drew similar results. Two-thirds of Republicans said that it was very/somewhat important for the government to trace the contacts of any person who tested positive for COVID-19, a sentiment shared by 91% of Democrats. That type of tracing was supported by 88% of blacks, 85% of Hispanics, and 79% of whites, based on the polling results.

The survey, conducted for the Commonwealth Fund by the survey and market research firm SSRS, had a margin of error of ± 2.4 percentage points.

rfranki@mdedge.com

Most Americans support the required use of face masks in public, along with universal COVID-19 testing, to provide a safe work environment during the pandemic, according to a new report from the Commonwealth Fund.

Results of a recent survey show that 85% of adults believe that it is very or somewhat important to require everyone to wear a face mask “at work, when shopping, and on public transportation,” said Sara R. Collins, PhD, vice president for health care coverage and access at the fund, and associates.

In that survey, conducted from May 13 to June 2, 2020, and involving 2,271 respondents, regular COVID-19 testing for everyone was supported by 81% of the sample as way to ensure a safe work environment until a vaccine is available, the researchers said in the report.

Support on both issues was consistently high across both racial/ethnic and political lines. Mandatory mask use gained 91% support among black respondents, 90% in Hispanics, and 82% in whites. There was greater distance between the political parties, but 70% of Republicans and Republican-leaning independents support mask use, compared with 95% of Democrats and Democratic-leaning independents, they said.

Regarding regular testing, 66% of Republicans and those leaning Republican said that it was very/somewhat important to ensure a safe work environment, as did 91% on the Democratic side. Hispanics offered the most support by race/ethnicity, with 90% saying that testing was very/somewhat important, compared with 86% of black respondents and 78% of white respondents, Dr. Collins and associates said.

A question on contact tracing drew similar results. Two-thirds of Republicans said that it was very/somewhat important for the government to trace the contacts of any person who tested positive for COVID-19, a sentiment shared by 91% of Democrats. That type of tracing was supported by 88% of blacks, 85% of Hispanics, and 79% of whites, based on the polling results.

The survey, conducted for the Commonwealth Fund by the survey and market research firm SSRS, had a margin of error of ± 2.4 percentage points.

rfranki@mdedge.com

Most Americans support the required use of face masks in public, along with universal COVID-19 testing, to provide a safe work environment during the pandemic, according to a new report from the Commonwealth Fund.

Results of a recent survey show that 85% of adults believe that it is very or somewhat important to require everyone to wear a face mask “at work, when shopping, and on public transportation,” said Sara R. Collins, PhD, vice president for health care coverage and access at the fund, and associates.

In that survey, conducted from May 13 to June 2, 2020, and involving 2,271 respondents, regular COVID-19 testing for everyone was supported by 81% of the sample as way to ensure a safe work environment until a vaccine is available, the researchers said in the report.

Support on both issues was consistently high across both racial/ethnic and political lines. Mandatory mask use gained 91% support among black respondents, 90% in Hispanics, and 82% in whites. There was greater distance between the political parties, but 70% of Republicans and Republican-leaning independents support mask use, compared with 95% of Democrats and Democratic-leaning independents, they said.

Regarding regular testing, 66% of Republicans and those leaning Republican said that it was very/somewhat important to ensure a safe work environment, as did 91% on the Democratic side. Hispanics offered the most support by race/ethnicity, with 90% saying that testing was very/somewhat important, compared with 86% of black respondents and 78% of white respondents, Dr. Collins and associates said.

A question on contact tracing drew similar results. Two-thirds of Republicans said that it was very/somewhat important for the government to trace the contacts of any person who tested positive for COVID-19, a sentiment shared by 91% of Democrats. That type of tracing was supported by 88% of blacks, 85% of Hispanics, and 79% of whites, based on the polling results.

The survey, conducted for the Commonwealth Fund by the survey and market research firm SSRS, had a margin of error of ± 2.4 percentage points.

rfranki@mdedge.com

A new review outlined a three-stage classification of the impact of COVID-19 on the central nervous system and recommended all hospitalized patients with the virus undergo MRI to flag potential neurologic damage and inform postdischarge monitoring.

In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.

“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.

“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.

The review was published online June 8 in the Journal of Alzheimer’s Disease.
 

Wreaks CNS havoc

It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.

They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”

These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.

If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.

“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.

“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
 

Three-stage classification

• Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
• Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
• Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.

“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.

“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.

“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.

As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.

Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.

“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
 

Routine MRI not necessary

Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.

“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.

Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”

Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”

The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.

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

A new review outlined a three-stage classification of the impact of COVID-19 on the central nervous system and recommended all hospitalized patients with the virus undergo MRI to flag potential neurologic damage and inform postdischarge monitoring.

In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.

“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.

“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.

The review was published online June 8 in the Journal of Alzheimer’s Disease.
 

Wreaks CNS havoc

It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.

They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”

These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.

If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.

“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.

“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
 

Three-stage classification

• Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
• Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
• Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.

“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.

“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.

“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.

As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.

Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.

“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
 

Routine MRI not necessary

Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.

“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.

Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”

Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”

The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.

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

A new review outlined a three-stage classification of the impact of COVID-19 on the central nervous system and recommended all hospitalized patients with the virus undergo MRI to flag potential neurologic damage and inform postdischarge monitoring.

In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.

“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.

“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.

The review was published online June 8 in the Journal of Alzheimer’s Disease.
 

Wreaks CNS havoc

It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.

They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”

These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.

If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.

“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.

“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
 

Three-stage classification

• Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
• Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
• Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.

“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.

“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.

“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.

As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.

Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.

“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
 

Routine MRI not necessary

Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.

“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.

Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”

Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”

The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.

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

Here are the stories our MDedge editors across specialties think you need to know about today:

Many physicians live within their means and save

Although about two of five physicians report a net worth of between $1 million and $5 million, about half report that they are living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

Net worth figures varied greatly by specialty. Among specialists, orthopedists were most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%). Conversely, 46% of family physicians and 44% of pediatricians reported that their net worth was under $500,000. Gender gaps were also apparent in the data, especially at the highest levels. Twice as many male physicians (10%) as their female counterparts (5%) had a net worth of more than $5 million.

Asked about saving habits, 43% of physicians reported they live below their means. Just 7% said they live above their means. How do they save money? Survey respondents reported putting bonus money into an investment account, putting extra money toward paying down the mortgage, and bringing lunch to work everyday.

The survey responses on salary, debt, and net worth from more than 17,000 physicians spanning 30 specialties were collected prior to Feb. 11, before COVID-19 was declared a pandemic. Read more.
 

Phase 3 COVID-19 vaccine trials launching in July

There are now 120 Investigational New Drug applications to the Food and Drug Administration for a SARS-CoV-2 vaccine, and researchers at more than 70 companies across the globe are interested in making a vaccine, according to Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.” Read more.

FDA approves in-home breast cancer treatment

The Food and Drug Administration has approved a combination of subcutaneous breast cancer treatments that could be administered at home, following completion of chemotherapy.

The agency gave the green light to pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche), administered subcutaneously rather than intravenously, for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete. Read more.

Could a visual tool aid migraine management?

A new visual tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines.

The tool is still just a prototype, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors from depression to insomnia.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” lead researcher Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, said in an interview.

Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Many physicians live within their means and save

Although about two of five physicians report a net worth of between $1 million and $5 million, about half report that they are living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

Net worth figures varied greatly by specialty. Among specialists, orthopedists were most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%). Conversely, 46% of family physicians and 44% of pediatricians reported that their net worth was under $500,000. Gender gaps were also apparent in the data, especially at the highest levels. Twice as many male physicians (10%) as their female counterparts (5%) had a net worth of more than $5 million.

Asked about saving habits, 43% of physicians reported they live below their means. Just 7% said they live above their means. How do they save money? Survey respondents reported putting bonus money into an investment account, putting extra money toward paying down the mortgage, and bringing lunch to work everyday.

The survey responses on salary, debt, and net worth from more than 17,000 physicians spanning 30 specialties were collected prior to Feb. 11, before COVID-19 was declared a pandemic. Read more.
 

Phase 3 COVID-19 vaccine trials launching in July

There are now 120 Investigational New Drug applications to the Food and Drug Administration for a SARS-CoV-2 vaccine, and researchers at more than 70 companies across the globe are interested in making a vaccine, according to Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.” Read more.

FDA approves in-home breast cancer treatment

The Food and Drug Administration has approved a combination of subcutaneous breast cancer treatments that could be administered at home, following completion of chemotherapy.

The agency gave the green light to pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche), administered subcutaneously rather than intravenously, for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete. Read more.

Could a visual tool aid migraine management?

A new visual tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines.

The tool is still just a prototype, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors from depression to insomnia.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” lead researcher Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, said in an interview.

Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Many physicians live within their means and save

Although about two of five physicians report a net worth of between $1 million and $5 million, about half report that they are living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

Net worth figures varied greatly by specialty. Among specialists, orthopedists were most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%). Conversely, 46% of family physicians and 44% of pediatricians reported that their net worth was under $500,000. Gender gaps were also apparent in the data, especially at the highest levels. Twice as many male physicians (10%) as their female counterparts (5%) had a net worth of more than $5 million.

Asked about saving habits, 43% of physicians reported they live below their means. Just 7% said they live above their means. How do they save money? Survey respondents reported putting bonus money into an investment account, putting extra money toward paying down the mortgage, and bringing lunch to work everyday.

The survey responses on salary, debt, and net worth from more than 17,000 physicians spanning 30 specialties were collected prior to Feb. 11, before COVID-19 was declared a pandemic. Read more.
 

Phase 3 COVID-19 vaccine trials launching in July

There are now 120 Investigational New Drug applications to the Food and Drug Administration for a SARS-CoV-2 vaccine, and researchers at more than 70 companies across the globe are interested in making a vaccine, according to Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.” Read more.

FDA approves in-home breast cancer treatment

The Food and Drug Administration has approved a combination of subcutaneous breast cancer treatments that could be administered at home, following completion of chemotherapy.

The agency gave the green light to pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche), administered subcutaneously rather than intravenously, for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete. Read more.

Could a visual tool aid migraine management?

A new visual tool aims to streamline patient-clinician communication about risk factors for progression from episodic to chronic migraines.

The tool is still just a prototype, but it could eventually synthesize patient responses to an integrated questionnaire and produce a chart illustrating where the patient stands with respect to a range of modifiable risk factors from depression to insomnia.

Physicians must see patients in short appointment periods, making it difficult to communicate all of the risk factors and behavioral characteristics that can contribute to risk of progression. “If you have a patient and you’re able to look at a visualization tool quickly and say: ‘Okay, my patient really is having insomnia and sleep issues,’ you can focus the session talking about sleep, cognitive-behavioral therapy for insomnia, and all the things we can help patients with,” lead researcher Ami Cuneo, MD, who is a headache fellow at the University of Washington, Seattle, said in an interview.

Dr. Cuneo presented a poster describing the concept at the virtual annual meeting of the American Headache Society. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

The oral selective estrogen receptor degrader (SERD) LSZ102 plus either ribociclib or alpelisib shows manageable safety and encouraging clinical activity in heavily pretreated estrogen receptor (ER)–positive breast cancer patients who progressed after prior endocrine therapy, according to interim results of an open-label phase 1/1b study.

The effects seen in the study, which is the first to report on an oral SERD in combination with both CDK4/6 and PI3Ka inhibitors, occurred regardless of ESR1 and PIK3CA mutations, said Komal Jhaveri, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Jhaveri reported the results at the European Society of Medical Oncology: Breast Cancer virtual meeting.

The overall response rate (ORR) among 78 patients enrolled in an LSZ102 monotherapy arm (arm A) was 1.3%, and the progression-free survival (PFS) was 1.8 months. The clinical benefit rate (CBR) was 9.1%.

Among 76 patients enrolled in an LSZ102+ribociclib arm (arm B), the ORR was 15.8%, the PFS was 6.2 months, and the CBR was 35.5%.

Among the 39 patients enrolled in an LSZ102+alpelisib arm (arm C), the ORR was 5.4%, the PFS was 3.5 months, and the CBR was 18.9%.

After the data cutoff, one additional partial response (PR) was reported in arm C, Dr. Jhaveri said, noting that two of three confirmed responses were in known PIKC3A-mutant patients.

Study participants were aged 18 years and older with a confirmed diagnosis of ER-positive breast cancer and good performance status, as well as evidence of progression after endocrine therapy for metastatic disease or evidence of progression while on therapy or within 12 months from the end of adjuvant therapy.

“For all arms, prior fulvestrant, CDK46 inhibitor, or chemotherapy were allowed. For arm C, patients with or without PIK3C were eligible, and no prior treatment with PIK3, mTOR, or AKT inhibitors was allowed,” Dr. Jhaveri said.

Dosing in the LSZ102 monotherapy arm ranged from 200 to 900 mg. Arm B patients received LSZ102 at doses of 200-600 mg and ribociclib at doses of 200-600 mg. Both continuous ribociclib and 3 weeks on/1 week off dosing were evaluated. Arm C patients received LSZ102 at doses of 300-450 mg and alpelisib at 200-300 mg.

The recommended expansion doses were 450 mg daily of LSZ102 for arm A and 450 mg LSZ102 with 400 mg of daily ribociclib for arm B. For arm C, they were 300 mg LSZ102 with 250 mg of alpelisib daily.

Of note, two of three patients with a PR in arm C had received 300 mg LSZ102 and 300 mg alpelisib, Dr. Jhaveri said.

Arm A and arm B results were presented at the San Antonio Breast Cancer Symposium in 2018 and 2019, respectively. The current report updates those findings and presents arm C data for the first time, Dr. Jhaveri said.

LSZ102 was relatively well-tolerated as a single agent and in combination with ribociclib and alpelisib, according to Dr. Jhaveri. The most frequent adverse events were gastrointestinal toxicities, including nausea, vomiting, diarrhea, and decreased appetite, which occurred across all arms.

Neutropenia and aspartate aminotransferase abnormalities, including grade 3 cases, were reported in arm B and were most likely driven by the ribociclib, Dr. Jhaveri said. Grade 3 hypoglycemia and skin rash commonly occurred in arm C, most likely driven by the alpelisib.

Five dose-limiting toxicities occurred in four patients in arm A, three occurred in two patients in arm B, and seven occurred in seven patients in arm C.

Paired biopsies collected at the time of screening and at day 15 of cycle 1 showed consistent down-regulation of ER protein levels across arms.

“No substantial dose-dependent down-regulation of the ER was observed with increasing doses of LSZ,” Dr. Jhaveri said.

Circulating tumor DNA (ctDNA) analysis showed that the dominant mutations across the arms were ESR1, PIK3CA, and TP53. These were not shown to correlate with response and were not enriched upon progression in patients with matched baseline and end-of-treatment samples, she noted.

An exploratory analysis, conducted in “a preliminary attempt to correlate clinical activity with specific mutations,” showed that, in arms B and C, respectively, ORR, CBR, and PFS weren’t correlated with the presence or absence of ESR1 and PIK3CA mutations, respectively, or the absence of detectable ctDNA from baseline samples, Dr. Jhaveri said.

“While numerically higher responses and better CBR were seen in patients with undetectable ctDNA at baseline, no statistically significant difference in any of these outcomes was observed in arms B and C,” she said.

In arm C, the numbers were small at the time of data cutoff, but incoming data suggest relatively enhanced activity of the LSZ102 plus alpelisib combination in PIKC3A-mutant patients, she noted.

“We know that inhibiting ER signaling is the mainstay of treatment for ER-positive breast cancer,” Dr. Jhaveri explained, adding that aromatase inhibitors, estrogen receptor modulators, and SERDs are important classes of antiestrogenic agents, but fulvestrant is the only approved SERD. These are effective, but many patients develop resistance, she said.

“Proposed mechanisms for endocrine resistance include activation of the cell-cycle and cell-survival signaling pathways, or of the PI3K-AKT-mTOR pathway,” Dr. Jhaveri said. “To that end, ribociclib, a CDK46 inhibitor plus fulvestrant improved survival compared to fulvestrant alone in patients with ER-positive metastatic breast cancer.”

More recently, the PI3K inhibitor alpelisib plus fulvestrant also nearly doubled PFS vs. fulvestrant alone in PIKC3A-mutant, ER-positive metastatic breast cancer, which led to the approval of the combination in the United States.

Another mechanism of endocrine resistance includes acquisition of activating mutations in the estrogen receptor gene itself that allow tumors to survive and proliferate without depending on estrogen.

EGFR mutations appear to predict resistance to aromatase inhibitor therapies, but not outcomes in patients treated with fulvestrant. However, fulvestrant, which is delivered by intramuscular injection, has its own limitations, Dr. Jhaveri said.

“LSZ102 is a novel SERD that could achieve higher exposure than fulvestrant, leading to enhanced efficacy,” she said, noting that it was shown in preclinical models to have activity and to be synergistic in combination with ribociclib and alpelisib, forming the basis for the current study.

Invited discussant, Saverio Cinieri, MD, of Ospedale Antonio Perrino, Brindisi, Italy, said the study “elegantly demonstrated that estrogen receptor protein is down-regulated by LSZ102; [that] the genomic landscape of heavily pretreated patients is dominated by mutations in ESR1, PIK3CA, and TP53; [that] common mutations do not correlate with response and are not enriched on progression; [and that] ctDNA analysis at baseline shows similar outcomes with LSZ plus ribociclib or alpelisib, regardless of mutational status.”

LSZ102 is one of four new-generation SERDs in early-phase studies, he said, concluding that “in the COVID-19 era, the use of oral therapies will be even more necessary to limit access to the hospital.”

Dr. Cinieri also said that overcoming the limitations “of a molecule like the intramuscularly administered fulvestrant goes in this direction,” and that “the clinical efficacy and the biomolecular profile of LSZ102 seems to be able to meet these real needs.”

This study was funded by Novartis. Dr. Jhaveri reported advisory and consultancy roles and/or research grants or other funding to her institution from Novartis, ADC Therapeutics, Pfizer, and numerous other pharmaceutical and biotechnology companies. Dr. Cinieri reported relationships with Lily Oncology, Pfizer, Roche, AstraZeneca, Amgen, Novartis, including honoraria, grant and research support to his institution, advisory board participation, and scientific meeting support.

sworcester@mdedge.com

SOURCE: Jhaveri K et al. ESMO Breast Cancer, Abstract LBA1.

Planning for reduced use of opioids in pain management involves identifying appropriate patients and managing their expectations, according to according to Timothy E. Miller, MB, ChB, FRCA, of Duke University, Durham, N.C., who is president of the American Society for Enhanced Recovery.

Multimodal analgesia plans can be a beneficial part of enhanced recovery and may reduce or eliminate the need for opioids in some patients, he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

Dr. Miller shared a treatment algorithm for achieving optimal analgesia in patients after colorectal surgery that combines intravenous or oral analgesia with local anesthetics and additional nonopioid options. The algorithm involves choosing NSAIDs, acetaminophen, or gabapentin for IV/oral use. In addition, options for local anesthetic include with a choice of single-shot transversus abdominis plane (TAP) block.

Careful patient selection is key to an opioid-free or opioid reduced anesthetic strategy, Dr. Miller said. The appropriate patients have “no chronic opioids, no anxiety, and the desire to avoid opioid side effects,” he said.

Opioid-free or opioid-reduced strategies include realigning patient expectations to prepare for pain at a level of 2-4 on a scale of 10 as “expected and reasonable,” he said. Patients given no opioids or reduced opioids may report cramping after laparoscopic surgery, as well as shoulder pain that is referred from the CO₂ bubble under the diaphragm, he said. However, opioids don’t treat the shoulder pain well, and “walking or changing position usually relieves this pain,” and it usually resolves within 24 hours, Dr. Miller noted. “Just letting the patient know what is expected in terms of pain relief in their recovery is hugely important,” he said.

The optimal analgesia after surgery is a plan that combines optimized patient comfort with the fastest functional recovery and the fewest side effects, he emphasized.

Optimized patient comfort includes optimal pain ratings at rest and with movement, a decreasing impact of pain on emotion, function, and sleep disruption, and an improvement in the patient experience, he said. The fastest functional recovery is defined as a return to drinking liquids, eating solid foods, performing activities of daily living, and maintaining normal bladder, bowel, and cognitive function. Side effects to be considered in analgesia included nausea, vomiting, sedation, ileus, itching, dizziness, and delirium, he said.

In an unpublished study, Dr. Miller and colleagues eliminated opioids intraoperatively in a series of 56 cases of laparoscopic cholecystectomy and found significantly less opioids needed in the postanesthesia care unit (PACU). In addition, opioid-free patients had significantly shorter length of stay in the PACU, he said. “We are writing this up for publication and looking into doing larger studies,” Dr. Miller said.

Questions include whether the opioid-free technique translates more broadly, he said.

In addition, it is important to continue to collect data and study methods to treat pain and reduce opioid use perioperatively, Dr. Miller said. Some ongoing concerns include data surrounding the use of gabapentin and possible association with respiratory depression, he noted. Several meta-analyses have suggested that “gabapentinoids (gabapentin, pregabalin) when given as a single dose preoperatively are associated with a decrease in postoperative pain and opioid consumption at 24 hours,” said Dr. Miller. “When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients,” he said.

Overall, opioid-free anesthesia is both feasible and appropriate in certain patient populations, Dr. Miller concluded. “Implement your pathway and measure your outcomes with timely feedback so you can revise your protocol based on data,” he emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Miller disclosed relationships with Edwards Lifesciences, and serving as a board member for the Perioperative Quality Initiative and as a founding member of the Morpheus Consortium.

Planning for reduced use of opioids in pain management involves identifying appropriate patients and managing their expectations, according to according to Timothy E. Miller, MB, ChB, FRCA, of Duke University, Durham, N.C., who is president of the American Society for Enhanced Recovery.

Multimodal analgesia plans can be a beneficial part of enhanced recovery and may reduce or eliminate the need for opioids in some patients, he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

Dr. Miller shared a treatment algorithm for achieving optimal analgesia in patients after colorectal surgery that combines intravenous or oral analgesia with local anesthetics and additional nonopioid options. The algorithm involves choosing NSAIDs, acetaminophen, or gabapentin for IV/oral use. In addition, options for local anesthetic include with a choice of single-shot transversus abdominis plane (TAP) block.

Careful patient selection is key to an opioid-free or opioid reduced anesthetic strategy, Dr. Miller said. The appropriate patients have “no chronic opioids, no anxiety, and the desire to avoid opioid side effects,” he said.

Opioid-free or opioid-reduced strategies include realigning patient expectations to prepare for pain at a level of 2-4 on a scale of 10 as “expected and reasonable,” he said. Patients given no opioids or reduced opioids may report cramping after laparoscopic surgery, as well as shoulder pain that is referred from the CO₂ bubble under the diaphragm, he said. However, opioids don’t treat the shoulder pain well, and “walking or changing position usually relieves this pain,” and it usually resolves within 24 hours, Dr. Miller noted. “Just letting the patient know what is expected in terms of pain relief in their recovery is hugely important,” he said.

The optimal analgesia after surgery is a plan that combines optimized patient comfort with the fastest functional recovery and the fewest side effects, he emphasized.

Optimized patient comfort includes optimal pain ratings at rest and with movement, a decreasing impact of pain on emotion, function, and sleep disruption, and an improvement in the patient experience, he said. The fastest functional recovery is defined as a return to drinking liquids, eating solid foods, performing activities of daily living, and maintaining normal bladder, bowel, and cognitive function. Side effects to be considered in analgesia included nausea, vomiting, sedation, ileus, itching, dizziness, and delirium, he said.

In an unpublished study, Dr. Miller and colleagues eliminated opioids intraoperatively in a series of 56 cases of laparoscopic cholecystectomy and found significantly less opioids needed in the postanesthesia care unit (PACU). In addition, opioid-free patients had significantly shorter length of stay in the PACU, he said. “We are writing this up for publication and looking into doing larger studies,” Dr. Miller said.

Questions include whether the opioid-free technique translates more broadly, he said.

In addition, it is important to continue to collect data and study methods to treat pain and reduce opioid use perioperatively, Dr. Miller said. Some ongoing concerns include data surrounding the use of gabapentin and possible association with respiratory depression, he noted. Several meta-analyses have suggested that “gabapentinoids (gabapentin, pregabalin) when given as a single dose preoperatively are associated with a decrease in postoperative pain and opioid consumption at 24 hours,” said Dr. Miller. “When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients,” he said.

Overall, opioid-free anesthesia is both feasible and appropriate in certain patient populations, Dr. Miller concluded. “Implement your pathway and measure your outcomes with timely feedback so you can revise your protocol based on data,” he emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Miller disclosed relationships with Edwards Lifesciences, and serving as a board member for the Perioperative Quality Initiative and as a founding member of the Morpheus Consortium.

Planning for reduced use of opioids in pain management involves identifying appropriate patients and managing their expectations, according to according to Timothy E. Miller, MB, ChB, FRCA, of Duke University, Durham, N.C., who is president of the American Society for Enhanced Recovery.

Multimodal analgesia plans can be a beneficial part of enhanced recovery and may reduce or eliminate the need for opioids in some patients, he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

Dr. Miller shared a treatment algorithm for achieving optimal analgesia in patients after colorectal surgery that combines intravenous or oral analgesia with local anesthetics and additional nonopioid options. The algorithm involves choosing NSAIDs, acetaminophen, or gabapentin for IV/oral use. In addition, options for local anesthetic include with a choice of single-shot transversus abdominis plane (TAP) block.

Careful patient selection is key to an opioid-free or opioid reduced anesthetic strategy, Dr. Miller said. The appropriate patients have “no chronic opioids, no anxiety, and the desire to avoid opioid side effects,” he said.

Opioid-free or opioid-reduced strategies include realigning patient expectations to prepare for pain at a level of 2-4 on a scale of 10 as “expected and reasonable,” he said. Patients given no opioids or reduced opioids may report cramping after laparoscopic surgery, as well as shoulder pain that is referred from the CO₂ bubble under the diaphragm, he said. However, opioids don’t treat the shoulder pain well, and “walking or changing position usually relieves this pain,” and it usually resolves within 24 hours, Dr. Miller noted. “Just letting the patient know what is expected in terms of pain relief in their recovery is hugely important,” he said.

The optimal analgesia after surgery is a plan that combines optimized patient comfort with the fastest functional recovery and the fewest side effects, he emphasized.

Optimized patient comfort includes optimal pain ratings at rest and with movement, a decreasing impact of pain on emotion, function, and sleep disruption, and an improvement in the patient experience, he said. The fastest functional recovery is defined as a return to drinking liquids, eating solid foods, performing activities of daily living, and maintaining normal bladder, bowel, and cognitive function. Side effects to be considered in analgesia included nausea, vomiting, sedation, ileus, itching, dizziness, and delirium, he said.

In an unpublished study, Dr. Miller and colleagues eliminated opioids intraoperatively in a series of 56 cases of laparoscopic cholecystectomy and found significantly less opioids needed in the postanesthesia care unit (PACU). In addition, opioid-free patients had significantly shorter length of stay in the PACU, he said. “We are writing this up for publication and looking into doing larger studies,” Dr. Miller said.

Questions include whether the opioid-free technique translates more broadly, he said.

In addition, it is important to continue to collect data and study methods to treat pain and reduce opioid use perioperatively, Dr. Miller said. Some ongoing concerns include data surrounding the use of gabapentin and possible association with respiratory depression, he noted. Several meta-analyses have suggested that “gabapentinoids (gabapentin, pregabalin) when given as a single dose preoperatively are associated with a decrease in postoperative pain and opioid consumption at 24 hours,” said Dr. Miller. “When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients,” he said.

Overall, opioid-free anesthesia is both feasible and appropriate in certain patient populations, Dr. Miller concluded. “Implement your pathway and measure your outcomes with timely feedback so you can revise your protocol based on data,” he emphasized.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Miller disclosed relationships with Edwards Lifesciences, and serving as a board member for the Perioperative Quality Initiative and as a founding member of the Morpheus Consortium.

The race to develop a SARS-CoV-2 vaccine is unlike any other global research and development effort in modern medicine.

According to Paul A. Offit, MD, there are now 120 Investigational New Drug applications to the Food and Drug Administration for these vaccines, and researchers at more than 70 companies across the globe are interested in making a vaccine. The Biomedical Advanced Research and Development Authority (BARDA) has awarded $2.5 billion to five different pharmaceutical companies to make a vaccine.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.”

Some research groups are interested in developing a whole, killed virus like those used in the inactivated polio vaccine, and vaccines for hepatitis A virus and rabies, said Dr. Offit, who is a member of Accelerating COVID-19 Technical Innovations And Vaccines, a public-private partnership formed by the National Institutes of Health. Other groups are interested in making a live-attenuated vaccine like those for measles, mumps, and rubella. “Some are interested in using a vectored vaccine, where you take a virus that is relatively weak and doesn’t cause disease in people, like vesicular stomatitis virus, and then clone into that the gene that codes for this coronavirus spike protein, which is the way that we made the Ebola virus vaccine,” Dr. Offit said. “Those approaches have all been used before, with success.”

Novel approaches are also being employed to make this vaccine, including using a replication-defective adenovirus. “That means that the virus can’t reproduce itself, but it can make proteins,” he explained. “There are some proteins that are made, but most aren’t. Therefore, the virus can’t reproduce itself. We’ll see whether or not that [approach] works, but it’s never been used before.”

Another approach is to inject messenger RNA that codes for the coronavirus spike protein, where that genetic material is translated into the spike protein. The other platform being evaluated is a DNA vaccine, in which “you give DNA which is coded for that spike protein, which is transcribed to messenger RNA and then is translated to other proteins.”

Typical vaccine development involves animal models to prove the concept, dose-ranging studies in humans, and progressively larger safety and immunogenicity studies in hundreds of thousands of people. Next come phase 3 studies, “where the proof is in the pudding,” he said. “These are large, prospective placebo-controlled trials to prove that the vaccine is safe. This is the only way whether you can prove or not a vaccine is effective.”

According to Dr. Offit, the phase 3 COVID-19 vaccine trials supported by BARDA will launch in July 2020 and will enroll 20,000 people in the vaccine treatment arm and 10,000 in the placebo arm. “Some companies may branch out on their own and do smaller studies than that,” he said. “We’ll see how this plays out. Keep your eyes open for that, because you really want to make sure you have a fairly large phase 3 trial. That’s the best way to show whether something works and whether it’s safe.”

The tried and true vaccines that emerge from the effort will not be FDA-licensed products. Rather, they will be approved products under the Emergency Use Authorization program. “Ever since the 1950s, every vaccine that has been used in the U.S. has been under the auspices of FDA licensure,” said Dr. Offit, who is also professor of pediatrics and the Maurice R. Hilleman professor of vaccinology at the University of Pennsylvania, Philadelphia. “That’s not going to be true here. The FDA is involved every step of the way but here they have a somewhat lighter touch.”

A few candidate vaccines are being mass-produced at risk, “meaning they’re being produced not knowing whether these vaccines are safe and effective yet or not,” he said. “But when they’re shown in a phase 3 trial to be safe and effective, you will have already produced it, and then it’s much easier to roll it out to the general public the minute you’ve shown that it works. This is what we did for the polio vaccine back in the 1950s. We mass-produced that vaccine at risk.”

Dr. Offit emphasized the importance of managing expectations once a COVID-19 vaccine gets approved for use. “Regarding safety, these vaccines will be tested in tens of thousands of people, not tens of millions of people, so although you can disprove a relatively uncommon side effect preapproval, you’re not going to disprove a rare side effect preapproval. You’re only going to know that post approval. I think we need to make people aware of that and to let them know that through groups like the Vaccine Safety Datalink, we’re going to be monitoring these vaccines once they’re approved.”

Regarding efficacy, he continued, “we’re not going know about the rates of immunity initially; we’re only going to know about that after the vaccine [has been administered]. My guess is the protection is going to be short lived and incomplete. By short lived, I mean that protection would last for years but not decades. By incomplete, I mean that protection will be against moderate to severe disease, which is fine. You don’t need protection against all of the disease; it’s hard to do that with respiratory viruses. That means you can keep people out of the hospital, and you can keep them from dying. That’s the main goal.”

Dr. Offit closed his remarks by noting that much is at stake in this effort to develop a vaccine so quickly and that it “could go one of two ways. We could find that the vaccine is a lifesaver, and [that] we can finally end this awful pandemic. Or, if we cut corners and don’t prove that the vaccines are safe and effective as we should before they’re released, we could shake what is a fragile vaccine confidence in this country. Hopefully, it doesn’t play out that way.”

dbrunk@mdedge.com

The race to develop a SARS-CoV-2 vaccine is unlike any other global research and development effort in modern medicine.

According to Paul A. Offit, MD, there are now 120 Investigational New Drug applications to the Food and Drug Administration for these vaccines, and researchers at more than 70 companies across the globe are interested in making a vaccine. The Biomedical Advanced Research and Development Authority (BARDA) has awarded $2.5 billion to five different pharmaceutical companies to make a vaccine.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.”

Some research groups are interested in developing a whole, killed virus like those used in the inactivated polio vaccine, and vaccines for hepatitis A virus and rabies, said Dr. Offit, who is a member of Accelerating COVID-19 Technical Innovations And Vaccines, a public-private partnership formed by the National Institutes of Health. Other groups are interested in making a live-attenuated vaccine like those for measles, mumps, and rubella. “Some are interested in using a vectored vaccine, where you take a virus that is relatively weak and doesn’t cause disease in people, like vesicular stomatitis virus, and then clone into that the gene that codes for this coronavirus spike protein, which is the way that we made the Ebola virus vaccine,” Dr. Offit said. “Those approaches have all been used before, with success.”

Novel approaches are also being employed to make this vaccine, including using a replication-defective adenovirus. “That means that the virus can’t reproduce itself, but it can make proteins,” he explained. “There are some proteins that are made, but most aren’t. Therefore, the virus can’t reproduce itself. We’ll see whether or not that [approach] works, but it’s never been used before.”

Another approach is to inject messenger RNA that codes for the coronavirus spike protein, where that genetic material is translated into the spike protein. The other platform being evaluated is a DNA vaccine, in which “you give DNA which is coded for that spike protein, which is transcribed to messenger RNA and then is translated to other proteins.”

Typical vaccine development involves animal models to prove the concept, dose-ranging studies in humans, and progressively larger safety and immunogenicity studies in hundreds of thousands of people. Next come phase 3 studies, “where the proof is in the pudding,” he said. “These are large, prospective placebo-controlled trials to prove that the vaccine is safe. This is the only way whether you can prove or not a vaccine is effective.”

According to Dr. Offit, the phase 3 COVID-19 vaccine trials supported by BARDA will launch in July 2020 and will enroll 20,000 people in the vaccine treatment arm and 10,000 in the placebo arm. “Some companies may branch out on their own and do smaller studies than that,” he said. “We’ll see how this plays out. Keep your eyes open for that, because you really want to make sure you have a fairly large phase 3 trial. That’s the best way to show whether something works and whether it’s safe.”

The tried and true vaccines that emerge from the effort will not be FDA-licensed products. Rather, they will be approved products under the Emergency Use Authorization program. “Ever since the 1950s, every vaccine that has been used in the U.S. has been under the auspices of FDA licensure,” said Dr. Offit, who is also professor of pediatrics and the Maurice R. Hilleman professor of vaccinology at the University of Pennsylvania, Philadelphia. “That’s not going to be true here. The FDA is involved every step of the way but here they have a somewhat lighter touch.”

A few candidate vaccines are being mass-produced at risk, “meaning they’re being produced not knowing whether these vaccines are safe and effective yet or not,” he said. “But when they’re shown in a phase 3 trial to be safe and effective, you will have already produced it, and then it’s much easier to roll it out to the general public the minute you’ve shown that it works. This is what we did for the polio vaccine back in the 1950s. We mass-produced that vaccine at risk.”

Dr. Offit emphasized the importance of managing expectations once a COVID-19 vaccine gets approved for use. “Regarding safety, these vaccines will be tested in tens of thousands of people, not tens of millions of people, so although you can disprove a relatively uncommon side effect preapproval, you’re not going to disprove a rare side effect preapproval. You’re only going to know that post approval. I think we need to make people aware of that and to let them know that through groups like the Vaccine Safety Datalink, we’re going to be monitoring these vaccines once they’re approved.”

Regarding efficacy, he continued, “we’re not going know about the rates of immunity initially; we’re only going to know about that after the vaccine [has been administered]. My guess is the protection is going to be short lived and incomplete. By short lived, I mean that protection would last for years but not decades. By incomplete, I mean that protection will be against moderate to severe disease, which is fine. You don’t need protection against all of the disease; it’s hard to do that with respiratory viruses. That means you can keep people out of the hospital, and you can keep them from dying. That’s the main goal.”

Dr. Offit closed his remarks by noting that much is at stake in this effort to develop a vaccine so quickly and that it “could go one of two ways. We could find that the vaccine is a lifesaver, and [that] we can finally end this awful pandemic. Or, if we cut corners and don’t prove that the vaccines are safe and effective as we should before they’re released, we could shake what is a fragile vaccine confidence in this country. Hopefully, it doesn’t play out that way.”

dbrunk@mdedge.com

The race to develop a SARS-CoV-2 vaccine is unlike any other global research and development effort in modern medicine.

According to Paul A. Offit, MD, there are now 120 Investigational New Drug applications to the Food and Drug Administration for these vaccines, and researchers at more than 70 companies across the globe are interested in making a vaccine. The Biomedical Advanced Research and Development Authority (BARDA) has awarded $2.5 billion to five different pharmaceutical companies to make a vaccine.

“The good news is that the new coronavirus is relatively stable,” Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. “Although it is a single-stranded RNA virus, it does mutate to some extent, but it doesn’t look like it’s going to mutate away from the vaccine. So, this is not going to be like influenza virus, where you must give a vaccine every year. I think we can make a vaccine that will last for several years. And we know the protein we’re interested in. We’re interested in antibodies directed against the spike glycoprotein, which is abundantly present on the surface of the virus. We know that if we make an antibody response to that protein, we can therefore prevent infection.”

Some research groups are interested in developing a whole, killed virus like those used in the inactivated polio vaccine, and vaccines for hepatitis A virus and rabies, said Dr. Offit, who is a member of Accelerating COVID-19 Technical Innovations And Vaccines, a public-private partnership formed by the National Institutes of Health. Other groups are interested in making a live-attenuated vaccine like those for measles, mumps, and rubella. “Some are interested in using a vectored vaccine, where you take a virus that is relatively weak and doesn’t cause disease in people, like vesicular stomatitis virus, and then clone into that the gene that codes for this coronavirus spike protein, which is the way that we made the Ebola virus vaccine,” Dr. Offit said. “Those approaches have all been used before, with success.”

Novel approaches are also being employed to make this vaccine, including using a replication-defective adenovirus. “That means that the virus can’t reproduce itself, but it can make proteins,” he explained. “There are some proteins that are made, but most aren’t. Therefore, the virus can’t reproduce itself. We’ll see whether or not that [approach] works, but it’s never been used before.”

Another approach is to inject messenger RNA that codes for the coronavirus spike protein, where that genetic material is translated into the spike protein. The other platform being evaluated is a DNA vaccine, in which “you give DNA which is coded for that spike protein, which is transcribed to messenger RNA and then is translated to other proteins.”

Typical vaccine development involves animal models to prove the concept, dose-ranging studies in humans, and progressively larger safety and immunogenicity studies in hundreds of thousands of people. Next come phase 3 studies, “where the proof is in the pudding,” he said. “These are large, prospective placebo-controlled trials to prove that the vaccine is safe. This is the only way whether you can prove or not a vaccine is effective.”

According to Dr. Offit, the phase 3 COVID-19 vaccine trials supported by BARDA will launch in July 2020 and will enroll 20,000 people in the vaccine treatment arm and 10,000 in the placebo arm. “Some companies may branch out on their own and do smaller studies than that,” he said. “We’ll see how this plays out. Keep your eyes open for that, because you really want to make sure you have a fairly large phase 3 trial. That’s the best way to show whether something works and whether it’s safe.”

The tried and true vaccines that emerge from the effort will not be FDA-licensed products. Rather, they will be approved products under the Emergency Use Authorization program. “Ever since the 1950s, every vaccine that has been used in the U.S. has been under the auspices of FDA licensure,” said Dr. Offit, who is also professor of pediatrics and the Maurice R. Hilleman professor of vaccinology at the University of Pennsylvania, Philadelphia. “That’s not going to be true here. The FDA is involved every step of the way but here they have a somewhat lighter touch.”

A few candidate vaccines are being mass-produced at risk, “meaning they’re being produced not knowing whether these vaccines are safe and effective yet or not,” he said. “But when they’re shown in a phase 3 trial to be safe and effective, you will have already produced it, and then it’s much easier to roll it out to the general public the minute you’ve shown that it works. This is what we did for the polio vaccine back in the 1950s. We mass-produced that vaccine at risk.”

Dr. Offit emphasized the importance of managing expectations once a COVID-19 vaccine gets approved for use. “Regarding safety, these vaccines will be tested in tens of thousands of people, not tens of millions of people, so although you can disprove a relatively uncommon side effect preapproval, you’re not going to disprove a rare side effect preapproval. You’re only going to know that post approval. I think we need to make people aware of that and to let them know that through groups like the Vaccine Safety Datalink, we’re going to be monitoring these vaccines once they’re approved.”

Regarding efficacy, he continued, “we’re not going know about the rates of immunity initially; we’re only going to know about that after the vaccine [has been administered]. My guess is the protection is going to be short lived and incomplete. By short lived, I mean that protection would last for years but not decades. By incomplete, I mean that protection will be against moderate to severe disease, which is fine. You don’t need protection against all of the disease; it’s hard to do that with respiratory viruses. That means you can keep people out of the hospital, and you can keep them from dying. That’s the main goal.”

Dr. Offit closed his remarks by noting that much is at stake in this effort to develop a vaccine so quickly and that it “could go one of two ways. We could find that the vaccine is a lifesaver, and [that] we can finally end this awful pandemic. Or, if we cut corners and don’t prove that the vaccines are safe and effective as we should before they’re released, we could shake what is a fragile vaccine confidence in this country. Hopefully, it doesn’t play out that way.”

dbrunk@mdedge.com

Although about two of five physicians report a net worth of between $1 million and $5 million, half are under the million dollars and about half believe in living at or below their means, according to the latest Medscape Physician Debt and Net Worth Report 2020.

43% live below their means

Asked about habits regarding saving, 43% of physicians reported they live below their means. Half said they live at their means, and 7% said they live above their means.

Joel Greenwald, MD, CEO of Greenwald Wealth Management in St. Louis Park, Minn., recommends in the report trying to save 20% of annual gross salary.

More than a third of physicians who responded (39%) said they put more than $2,000/month into tax-deferred retirement or college savings, but Dr. Greenwald acknowledged that this may become more challenging.

“Many have seen the employer match in their retirement plans reduced or eliminated through the end of 2020, with what comes in 2021 as yet undefined,” he said.

A smaller percentage (26%) answered that they put more than $2,000 a month into a taxable retirement or college savings account each month.

Home size by specialty

Mortgages on a primary residence were the top reasons for debt (63%), followed by car loans (37%), personal education loans (26%), and credit card balances (25%).

Half of specialists and 61% of primary care physicians live in homes with up to 3,000 square feet. Only 7% of PCPs and 12% of specialists live in homes with 5000 square feet or more.

At 22%, plastic surgeons and orthopedists were the most likely groups to have houses with the largest square footage, according to the survey.

About one in four physicians in five specialties (urology, cardiology, plastic surgery, otolaryngology, and critical care) reported that they had mortgages of more than $500,000.

Standard financial advice, the report authors note, is that a mortgage should take up no more than 28% of monthly gross income.

Another large source of debt came from student loans. Close to 80% of graduating medical students have educational debt. The average balance for graduating students in 2018 was $196,520, the report authors state.

Those in physical medicine/rehabilitation and family medicine were most likely to still be paying off student debt (34% said they were). Conversely, half as many nephrologists and rheumatologists (15%) and gastroenterologists (14%) reported that they were paying off educational debt.

Only 11% of physicians said they were currently free of any debt.

Most physicians in the survey (72%) reported that they had not experienced a significant financial loss in the past year.

For those who did experience such a loss, the top reason given was related to a bad investment or the stock market (9%).
 

Cost-cutting strategies

Revenue reduction will likely lead to spending less this year as the pandemic challenges continue.

Survey respondents offered their most effective cost-cutting strategies.

A hospitalist said, “Half of every bonus goes into the investment account, no matter how much.”

“We add an extra amount to the principal of our monthly mortgage payment,” an internist said.

A pediatrician offered, “I bring my lunch to work every day and don’t eat in restaurants often.”
 

This article first appeared on Medscape.com.