A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

[email protected]

A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

[email protected]

A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

[email protected]

Patients hospitalized for sepsis are more likely to require readmission within a month after discharge if they live in disadvantaged neighborhoods, according to a study published in Critical Care Medicine.

The association between living in a disadvantaged neighborhood and 30-day readmission remained significant even after adjustment for “individual demographic variables, active tobacco use, length of index hospitalization, severity of acute and chronic morbidity, and place of initial discharge,” wrote Panagis Galiatsatos, MD, of Johns Hopkins University in Baltimore, and colleagues.

“Our findings suggest the need for interventions that emphasize neighborhood-level socioeconomic variables in addition to individual-level efforts in an effort to promote and achieve health equity for patients who survive a hospitalization due to sepsis,” the authors wrote. “With a third of our cohort rehospitalized with infections, and other studies emphasizing that the most common readmission diagnosis was infection, attention toward both anticipating and attenuating the risk of infection in sepsis survivors, especially among those who live in higher risk neighborhoods, must be a priority for the prevention of readmissions.”

Although she did not find the study results surprising, Eva DuGoff, PhD, a senior managing consultant with the Berkeley Research Group and a visiting assistant professor at University of Maryland School of Public Health, College Park, said in an interview that she was impressed with how clinically rigorous the analysis was, both in confirming an accurate sepsis diagnosis and in using the more refined measure of the Area Deprivation Index (ADI) to assess neighborhood disadvantage.

“I think it makes sense that people who have less means and are in neighborhoods with fewer resources would run into more issues and would need to return to the hospital, above and beyond the clinical risk factors, such as smoking and chronic conditions,” said Dr. DuGoff, who studies health disparities but was not involved in this study.

Shayla N.M. Durfey MD, ScM, a pediatric resident at Hasbro Children’s Hospital in Providence, R.I., said in an interview she was similarly unsurprised by the findings.

“People who live in disadvantaged neighborhoods may have less access to walking spaces, healthy food, and safe housing and more exposure to poor air quality, toxic stress, and violence – any of which can negatively impact health or recovery from illness through stress responses, nutritional deficiencies, or comorbidities, such as reactive airway disease, obesity, hypertension, and diabetes,” said Dr. Durfey, who studies health disparities but was not involved in this study. “Our research has found these neighborhood-level factors often matter above and beyond individual social determinants of health.”

Dr. Galiatsatos and associates conducted a retrospective study in Baltimore that compared readmission rates in 2017 at Johns Hopkins Bayview Medical Center among patients discharged after a hospitalization for sepsis, coded via ICD-10. They relied on the ADI to categorize the neighborhoods of patients’ residential addresses. The ADI rates various socioeconomic components, including income, education, employment, and housing characteristics, on a scale of 1-100 in geographic blocks, with higher score indicating a greater level of disadvantage.

Among 647 hospitalized patients with an ICD-10 code of sepsis who also met criteria for sepsis or septic shock per the Sepsis-3 definition, 17.9% were excluded from the analysis because they died or were transferred to hospice care. The other 531 patients had an average age of 61, and just under one-third (30.9%) were active smokers. Their average length of stay was 6.9 days, with a mean Charlson Comorbidity Index of 4.2 and a mean Sequential Organ Failure Assessment score of 4.9.

The average ADI for all the patients was 54.2, but the average score was 63 for the 22% of patients who were readmitted within 30 days of initial discharge, compared with an average 51.8 for patients not readmitted (P < .001).

Among those 117 readmitted, “39 patients had a reinfection, 68 had an exacerbation of their chronic conditions, and 10 were admitted for ‘concerning symptoms’ without a primary admitting diagnosis,” the investigators reported. Because “a third of our cohort was readmitted with an infection, it is possible that more disadvantaged neighborhoods created more challenges for a person’s immune system, which may be compromised after recovering from sepsis.”

Dr. DuGoff further noted that health literacy may be lower among people living in less advantaged neighborhoods.

“A number of studies suggest when patients leave the hospital, they’re not sure what they need to do. The language is complicated, and it’s hard to know what kind of medication to take when, and when you’re supposed to return to the doctor or the hospital,” Dr. DuGoff said. “Managing all of that can be pretty scary for people, particularly after a traumatic experience with sepsis at the hospital.”

Most patients had been discharged home (67.3%), but the 31.6% discharged to a skilled nursing facility had a greater likelihood of readmission, compared with those discharged home (P < .01); 1% were discharged to acute rehabilitation. The average length of stay during the index hospitalization was also greater for those readmitted (8.7 days) than for those not readmitted (6.4 days). The groups did not differ in terms of their acute organ dysfunction or severity of their comorbidities.

However, even after adjustment for these factors, “neighborhood disadvantage remained significantly associated with 30-day rehospitalization in patients who were discharged with sepsis,” the authors said. Specifically, each additional standard deviation greater in patients’ ADI was associated with increased risk of 30-day readmission (P < .001).

“Given that the ADI is a composite score, we cannot identify which component is the predominant driver of rehospitalizations for patients who survive sepsis,” the authors wrote. “However, all components that make up the index are intertwined, and policy efforts targeting one (i.e., unemployment) will likely impact others (i.e., housing).”

Dr. Durfey said that medical schools have not traditionally provided training related to management of social risk factors, although this is changing in more recent curricula. But the findings still have clinical relevance for practitioners.

“Certainly, the first step is awareness of where and how patients live and being mindful of how treatment plans may be impacted by social factors at both the individual and community levels,” Dr. Durfey said. “An important part of this is working in partnership with social workers and case managers. Importantly, clinicians can also partner with disadvantaged communities to advocate for improved conditions through policy change and act as expert witnesses to how neighborhood level factors impact health.”

Dr. DuGoff also wondered what implications these findings might have currently, with regards to COVID-19.

“People living in disadvantaged neighborhoods are already at higher risk for getting the disease, and this study raises really good questions about how we should be monitoring discharge now in anticipation of these types of issues,” she said.

The authors noted that their study is cross-sectional and cannot indicate causation, and the findings of a single urban institution may not be generalizable elsewhere. They also did not consider what interventions individual patients had during their index hospitalization that could have increased frailty.

The study did not note external funding. One coauthor of the study, Suchi Saria, PhD, reported receiving honoraria and travel reimbursement from two dozen biotechnology companies for keynotes and advisory board service; she also holds equity in Patient Ping and Bayesian Health. The other authors reported no industry disclosures. In addition to consulting for Berkeley Research Group, Dr. DuGoff has received a past honorarium from Zimmer Biomet. Dr. Durfey has no disclosures.

SOURCE: Galiatsatos P et al. Crit Care Med. 2020 Jun;48(6):808-14.

Patients hospitalized for sepsis are more likely to require readmission within a month after discharge if they live in disadvantaged neighborhoods, according to a study published in Critical Care Medicine.

The association between living in a disadvantaged neighborhood and 30-day readmission remained significant even after adjustment for “individual demographic variables, active tobacco use, length of index hospitalization, severity of acute and chronic morbidity, and place of initial discharge,” wrote Panagis Galiatsatos, MD, of Johns Hopkins University in Baltimore, and colleagues.

“Our findings suggest the need for interventions that emphasize neighborhood-level socioeconomic variables in addition to individual-level efforts in an effort to promote and achieve health equity for patients who survive a hospitalization due to sepsis,” the authors wrote. “With a third of our cohort rehospitalized with infections, and other studies emphasizing that the most common readmission diagnosis was infection, attention toward both anticipating and attenuating the risk of infection in sepsis survivors, especially among those who live in higher risk neighborhoods, must be a priority for the prevention of readmissions.”

Although she did not find the study results surprising, Eva DuGoff, PhD, a senior managing consultant with the Berkeley Research Group and a visiting assistant professor at University of Maryland School of Public Health, College Park, said in an interview that she was impressed with how clinically rigorous the analysis was, both in confirming an accurate sepsis diagnosis and in using the more refined measure of the Area Deprivation Index (ADI) to assess neighborhood disadvantage.

“I think it makes sense that people who have less means and are in neighborhoods with fewer resources would run into more issues and would need to return to the hospital, above and beyond the clinical risk factors, such as smoking and chronic conditions,” said Dr. DuGoff, who studies health disparities but was not involved in this study.

Shayla N.M. Durfey MD, ScM, a pediatric resident at Hasbro Children’s Hospital in Providence, R.I., said in an interview she was similarly unsurprised by the findings.

“People who live in disadvantaged neighborhoods may have less access to walking spaces, healthy food, and safe housing and more exposure to poor air quality, toxic stress, and violence – any of which can negatively impact health or recovery from illness through stress responses, nutritional deficiencies, or comorbidities, such as reactive airway disease, obesity, hypertension, and diabetes,” said Dr. Durfey, who studies health disparities but was not involved in this study. “Our research has found these neighborhood-level factors often matter above and beyond individual social determinants of health.”

Dr. Galiatsatos and associates conducted a retrospective study in Baltimore that compared readmission rates in 2017 at Johns Hopkins Bayview Medical Center among patients discharged after a hospitalization for sepsis, coded via ICD-10. They relied on the ADI to categorize the neighborhoods of patients’ residential addresses. The ADI rates various socioeconomic components, including income, education, employment, and housing characteristics, on a scale of 1-100 in geographic blocks, with higher score indicating a greater level of disadvantage.

Among 647 hospitalized patients with an ICD-10 code of sepsis who also met criteria for sepsis or septic shock per the Sepsis-3 definition, 17.9% were excluded from the analysis because they died or were transferred to hospice care. The other 531 patients had an average age of 61, and just under one-third (30.9%) were active smokers. Their average length of stay was 6.9 days, with a mean Charlson Comorbidity Index of 4.2 and a mean Sequential Organ Failure Assessment score of 4.9.

The average ADI for all the patients was 54.2, but the average score was 63 for the 22% of patients who were readmitted within 30 days of initial discharge, compared with an average 51.8 for patients not readmitted (P < .001).

Among those 117 readmitted, “39 patients had a reinfection, 68 had an exacerbation of their chronic conditions, and 10 were admitted for ‘concerning symptoms’ without a primary admitting diagnosis,” the investigators reported. Because “a third of our cohort was readmitted with an infection, it is possible that more disadvantaged neighborhoods created more challenges for a person’s immune system, which may be compromised after recovering from sepsis.”

Dr. DuGoff further noted that health literacy may be lower among people living in less advantaged neighborhoods.

“A number of studies suggest when patients leave the hospital, they’re not sure what they need to do. The language is complicated, and it’s hard to know what kind of medication to take when, and when you’re supposed to return to the doctor or the hospital,” Dr. DuGoff said. “Managing all of that can be pretty scary for people, particularly after a traumatic experience with sepsis at the hospital.”

Most patients had been discharged home (67.3%), but the 31.6% discharged to a skilled nursing facility had a greater likelihood of readmission, compared with those discharged home (P < .01); 1% were discharged to acute rehabilitation. The average length of stay during the index hospitalization was also greater for those readmitted (8.7 days) than for those not readmitted (6.4 days). The groups did not differ in terms of their acute organ dysfunction or severity of their comorbidities.

However, even after adjustment for these factors, “neighborhood disadvantage remained significantly associated with 30-day rehospitalization in patients who were discharged with sepsis,” the authors said. Specifically, each additional standard deviation greater in patients’ ADI was associated with increased risk of 30-day readmission (P < .001).

“Given that the ADI is a composite score, we cannot identify which component is the predominant driver of rehospitalizations for patients who survive sepsis,” the authors wrote. “However, all components that make up the index are intertwined, and policy efforts targeting one (i.e., unemployment) will likely impact others (i.e., housing).”

Dr. Durfey said that medical schools have not traditionally provided training related to management of social risk factors, although this is changing in more recent curricula. But the findings still have clinical relevance for practitioners.

“Certainly, the first step is awareness of where and how patients live and being mindful of how treatment plans may be impacted by social factors at both the individual and community levels,” Dr. Durfey said. “An important part of this is working in partnership with social workers and case managers. Importantly, clinicians can also partner with disadvantaged communities to advocate for improved conditions through policy change and act as expert witnesses to how neighborhood level factors impact health.”

Dr. DuGoff also wondered what implications these findings might have currently, with regards to COVID-19.

“People living in disadvantaged neighborhoods are already at higher risk for getting the disease, and this study raises really good questions about how we should be monitoring discharge now in anticipation of these types of issues,” she said.

The authors noted that their study is cross-sectional and cannot indicate causation, and the findings of a single urban institution may not be generalizable elsewhere. They also did not consider what interventions individual patients had during their index hospitalization that could have increased frailty.

The study did not note external funding. One coauthor of the study, Suchi Saria, PhD, reported receiving honoraria and travel reimbursement from two dozen biotechnology companies for keynotes and advisory board service; she also holds equity in Patient Ping and Bayesian Health. The other authors reported no industry disclosures. In addition to consulting for Berkeley Research Group, Dr. DuGoff has received a past honorarium from Zimmer Biomet. Dr. Durfey has no disclosures.

SOURCE: Galiatsatos P et al. Crit Care Med. 2020 Jun;48(6):808-14.

Patients hospitalized for sepsis are more likely to require readmission within a month after discharge if they live in disadvantaged neighborhoods, according to a study published in Critical Care Medicine.

The association between living in a disadvantaged neighborhood and 30-day readmission remained significant even after adjustment for “individual demographic variables, active tobacco use, length of index hospitalization, severity of acute and chronic morbidity, and place of initial discharge,” wrote Panagis Galiatsatos, MD, of Johns Hopkins University in Baltimore, and colleagues.

“Our findings suggest the need for interventions that emphasize neighborhood-level socioeconomic variables in addition to individual-level efforts in an effort to promote and achieve health equity for patients who survive a hospitalization due to sepsis,” the authors wrote. “With a third of our cohort rehospitalized with infections, and other studies emphasizing that the most common readmission diagnosis was infection, attention toward both anticipating and attenuating the risk of infection in sepsis survivors, especially among those who live in higher risk neighborhoods, must be a priority for the prevention of readmissions.”

Although she did not find the study results surprising, Eva DuGoff, PhD, a senior managing consultant with the Berkeley Research Group and a visiting assistant professor at University of Maryland School of Public Health, College Park, said in an interview that she was impressed with how clinically rigorous the analysis was, both in confirming an accurate sepsis diagnosis and in using the more refined measure of the Area Deprivation Index (ADI) to assess neighborhood disadvantage.

“I think it makes sense that people who have less means and are in neighborhoods with fewer resources would run into more issues and would need to return to the hospital, above and beyond the clinical risk factors, such as smoking and chronic conditions,” said Dr. DuGoff, who studies health disparities but was not involved in this study.

Shayla N.M. Durfey MD, ScM, a pediatric resident at Hasbro Children’s Hospital in Providence, R.I., said in an interview she was similarly unsurprised by the findings.

“People who live in disadvantaged neighborhoods may have less access to walking spaces, healthy food, and safe housing and more exposure to poor air quality, toxic stress, and violence – any of which can negatively impact health or recovery from illness through stress responses, nutritional deficiencies, or comorbidities, such as reactive airway disease, obesity, hypertension, and diabetes,” said Dr. Durfey, who studies health disparities but was not involved in this study. “Our research has found these neighborhood-level factors often matter above and beyond individual social determinants of health.”

Dr. Galiatsatos and associates conducted a retrospective study in Baltimore that compared readmission rates in 2017 at Johns Hopkins Bayview Medical Center among patients discharged after a hospitalization for sepsis, coded via ICD-10. They relied on the ADI to categorize the neighborhoods of patients’ residential addresses. The ADI rates various socioeconomic components, including income, education, employment, and housing characteristics, on a scale of 1-100 in geographic blocks, with higher score indicating a greater level of disadvantage.

Among 647 hospitalized patients with an ICD-10 code of sepsis who also met criteria for sepsis or septic shock per the Sepsis-3 definition, 17.9% were excluded from the analysis because they died or were transferred to hospice care. The other 531 patients had an average age of 61, and just under one-third (30.9%) were active smokers. Their average length of stay was 6.9 days, with a mean Charlson Comorbidity Index of 4.2 and a mean Sequential Organ Failure Assessment score of 4.9.

The average ADI for all the patients was 54.2, but the average score was 63 for the 22% of patients who were readmitted within 30 days of initial discharge, compared with an average 51.8 for patients not readmitted (P < .001).

Among those 117 readmitted, “39 patients had a reinfection, 68 had an exacerbation of their chronic conditions, and 10 were admitted for ‘concerning symptoms’ without a primary admitting diagnosis,” the investigators reported. Because “a third of our cohort was readmitted with an infection, it is possible that more disadvantaged neighborhoods created more challenges for a person’s immune system, which may be compromised after recovering from sepsis.”

Dr. DuGoff further noted that health literacy may be lower among people living in less advantaged neighborhoods.

“A number of studies suggest when patients leave the hospital, they’re not sure what they need to do. The language is complicated, and it’s hard to know what kind of medication to take when, and when you’re supposed to return to the doctor or the hospital,” Dr. DuGoff said. “Managing all of that can be pretty scary for people, particularly after a traumatic experience with sepsis at the hospital.”

Most patients had been discharged home (67.3%), but the 31.6% discharged to a skilled nursing facility had a greater likelihood of readmission, compared with those discharged home (P < .01); 1% were discharged to acute rehabilitation. The average length of stay during the index hospitalization was also greater for those readmitted (8.7 days) than for those not readmitted (6.4 days). The groups did not differ in terms of their acute organ dysfunction or severity of their comorbidities.

However, even after adjustment for these factors, “neighborhood disadvantage remained significantly associated with 30-day rehospitalization in patients who were discharged with sepsis,” the authors said. Specifically, each additional standard deviation greater in patients’ ADI was associated with increased risk of 30-day readmission (P < .001).

“Given that the ADI is a composite score, we cannot identify which component is the predominant driver of rehospitalizations for patients who survive sepsis,” the authors wrote. “However, all components that make up the index are intertwined, and policy efforts targeting one (i.e., unemployment) will likely impact others (i.e., housing).”

Dr. Durfey said that medical schools have not traditionally provided training related to management of social risk factors, although this is changing in more recent curricula. But the findings still have clinical relevance for practitioners.

“Certainly, the first step is awareness of where and how patients live and being mindful of how treatment plans may be impacted by social factors at both the individual and community levels,” Dr. Durfey said. “An important part of this is working in partnership with social workers and case managers. Importantly, clinicians can also partner with disadvantaged communities to advocate for improved conditions through policy change and act as expert witnesses to how neighborhood level factors impact health.”

Dr. DuGoff also wondered what implications these findings might have currently, with regards to COVID-19.

“People living in disadvantaged neighborhoods are already at higher risk for getting the disease, and this study raises really good questions about how we should be monitoring discharge now in anticipation of these types of issues,” she said.

The authors noted that their study is cross-sectional and cannot indicate causation, and the findings of a single urban institution may not be generalizable elsewhere. They also did not consider what interventions individual patients had during their index hospitalization that could have increased frailty.

The study did not note external funding. One coauthor of the study, Suchi Saria, PhD, reported receiving honoraria and travel reimbursement from two dozen biotechnology companies for keynotes and advisory board service; she also holds equity in Patient Ping and Bayesian Health. The other authors reported no industry disclosures. In addition to consulting for Berkeley Research Group, Dr. DuGoff has received a past honorarium from Zimmer Biomet. Dr. Durfey has no disclosures.

SOURCE: Galiatsatos P et al. Crit Care Med. 2020 Jun;48(6):808-14.

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.

Background: Type 2 diabetes is the leading cause of kidney failure worldwide. Few treatment options exist to help improve on this outcome in patients with chronic kidney disease.

Dr. Hoegh is a hospitalist at the University of Colorado at Denver, Aurora.

Background: Type 2 diabetes is the leading cause of kidney failure worldwide. Few treatment options exist to help improve on this outcome in patients with chronic kidney disease.

Dr. Hoegh is a hospitalist at the University of Colorado at Denver, Aurora.

Background: Type 2 diabetes is the leading cause of kidney failure worldwide. Few treatment options exist to help improve on this outcome in patients with chronic kidney disease.

Dr. Hoegh is a hospitalist at the University of Colorado at Denver, Aurora.

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.

[email protected]

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.

[email protected]

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.

[email protected]

This editorial is the first to be published in GI & Hepatology News since the murder of George Floyd in Minneapolis. The corner of 38th and Chicago is 9 miles from my home in Bloomington, Minn. This corner became the epicenter of protests that have spread around the nation and world. Early on, protests were accompanied by widespread riots, looting, and destruction. In the ensuing weeks, this corner has become a memorial for Mr. Floyd and a place where people now go to reflect, pray, pay tribute, and pledge to work for change.

A coalition of willing businesses has formed in the area around 38th and Chicago. The largest employer in the area is Allina Health (I sit on the Governing Board of Allina Health). Our flagship hospital is 8 blocks from the site of George Floyd’s memorial. We will be a change leader by committing funds for local rebuilding, ensuring use of construction firms that promote minority workers (as was done when the Viking’s stadium was built), examining our investment portfolio with racial equity as one guiding principle, increasing our focus on barriers to access, enhancing equity education of our workforce, and working with city and state leaders to promote police reform.

As the Editor in Chief of the official newspaper of the AGA, I invited our board of editors to stand united in our condemnation of the racial injustices that led to the protests we now see. We each agree with the message from the combined Governing Boards of our GI societies (published June 2, 2020) stating “As health care providers, we have dedicated our lives to caring for our fellow human beings. Therefore, we are compelled to speak out against any treatment that results in unacceptable disparities that marginalize the vulnerable among us.”

Our responsibility as editors is to guide the content we deliver, ensuring its relevancy to our readers. In this light, we commit to delivering content that highlights racial injustices and health disparities for all people, as we seek to understand the many factors that result in barriers to health. We will emphasize content that leads to impactful change and will highlight progress we make as a specialty. We hope our collective work will help ensure that George Floyd’s memory, and the memories of all such victims, become a catalyst for permanent cultural change.
 

Editor in Chief, GI & Hepatology News
John I. Allen, MD, MBA, AGAF

Editor in Chief, The New Gastroenterologist
Vijaya L. Rao, MD

Associate Editors
Megan A. Adams, MD, JD, MSc
Ziad Gellad, MD, MPH, AGAF
Kim L. Isaacs, MD, PhD, AGAF
Charles J. Kahi, MD, MS, AGAF
Gyanprakash A. Ketwaroo, MD, MSc
Larry R. Kosinski, MD, MBA, AGAF
Sonia S. Kupfer, MD
Wajahat Mehal, MD, PhD

This editorial is the first to be published in GI & Hepatology News since the murder of George Floyd in Minneapolis. The corner of 38th and Chicago is 9 miles from my home in Bloomington, Minn. This corner became the epicenter of protests that have spread around the nation and world. Early on, protests were accompanied by widespread riots, looting, and destruction. In the ensuing weeks, this corner has become a memorial for Mr. Floyd and a place where people now go to reflect, pray, pay tribute, and pledge to work for change.

A coalition of willing businesses has formed in the area around 38th and Chicago. The largest employer in the area is Allina Health (I sit on the Governing Board of Allina Health). Our flagship hospital is 8 blocks from the site of George Floyd’s memorial. We will be a change leader by committing funds for local rebuilding, ensuring use of construction firms that promote minority workers (as was done when the Viking’s stadium was built), examining our investment portfolio with racial equity as one guiding principle, increasing our focus on barriers to access, enhancing equity education of our workforce, and working with city and state leaders to promote police reform.

As the Editor in Chief of the official newspaper of the AGA, I invited our board of editors to stand united in our condemnation of the racial injustices that led to the protests we now see. We each agree with the message from the combined Governing Boards of our GI societies (published June 2, 2020) stating “As health care providers, we have dedicated our lives to caring for our fellow human beings. Therefore, we are compelled to speak out against any treatment that results in unacceptable disparities that marginalize the vulnerable among us.”

Our responsibility as editors is to guide the content we deliver, ensuring its relevancy to our readers. In this light, we commit to delivering content that highlights racial injustices and health disparities for all people, as we seek to understand the many factors that result in barriers to health. We will emphasize content that leads to impactful change and will highlight progress we make as a specialty. We hope our collective work will help ensure that George Floyd’s memory, and the memories of all such victims, become a catalyst for permanent cultural change.
 

Editor in Chief, GI & Hepatology News
John I. Allen, MD, MBA, AGAF

Editor in Chief, The New Gastroenterologist
Vijaya L. Rao, MD

Associate Editors
Megan A. Adams, MD, JD, MSc
Ziad Gellad, MD, MPH, AGAF
Kim L. Isaacs, MD, PhD, AGAF
Charles J. Kahi, MD, MS, AGAF
Gyanprakash A. Ketwaroo, MD, MSc
Larry R. Kosinski, MD, MBA, AGAF
Sonia S. Kupfer, MD
Wajahat Mehal, MD, PhD

This editorial is the first to be published in GI & Hepatology News since the murder of George Floyd in Minneapolis. The corner of 38th and Chicago is 9 miles from my home in Bloomington, Minn. This corner became the epicenter of protests that have spread around the nation and world. Early on, protests were accompanied by widespread riots, looting, and destruction. In the ensuing weeks, this corner has become a memorial for Mr. Floyd and a place where people now go to reflect, pray, pay tribute, and pledge to work for change.

A coalition of willing businesses has formed in the area around 38th and Chicago. The largest employer in the area is Allina Health (I sit on the Governing Board of Allina Health). Our flagship hospital is 8 blocks from the site of George Floyd’s memorial. We will be a change leader by committing funds for local rebuilding, ensuring use of construction firms that promote minority workers (as was done when the Viking’s stadium was built), examining our investment portfolio with racial equity as one guiding principle, increasing our focus on barriers to access, enhancing equity education of our workforce, and working with city and state leaders to promote police reform.

As the Editor in Chief of the official newspaper of the AGA, I invited our board of editors to stand united in our condemnation of the racial injustices that led to the protests we now see. We each agree with the message from the combined Governing Boards of our GI societies (published June 2, 2020) stating “As health care providers, we have dedicated our lives to caring for our fellow human beings. Therefore, we are compelled to speak out against any treatment that results in unacceptable disparities that marginalize the vulnerable among us.”

Our responsibility as editors is to guide the content we deliver, ensuring its relevancy to our readers. In this light, we commit to delivering content that highlights racial injustices and health disparities for all people, as we seek to understand the many factors that result in barriers to health. We will emphasize content that leads to impactful change and will highlight progress we make as a specialty. We hope our collective work will help ensure that George Floyd’s memory, and the memories of all such victims, become a catalyst for permanent cultural change.
 

Editor in Chief, GI & Hepatology News
John I. Allen, MD, MBA, AGAF

Editor in Chief, The New Gastroenterologist
Vijaya L. Rao, MD

Associate Editors
Megan A. Adams, MD, JD, MSc
Ziad Gellad, MD, MPH, AGAF
Kim L. Isaacs, MD, PhD, AGAF
Charles J. Kahi, MD, MS, AGAF
Gyanprakash A. Ketwaroo, MD, MSc
Larry R. Kosinski, MD, MBA, AGAF
Sonia S. Kupfer, MD
Wajahat Mehal, MD, PhD

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

Phase 3 trial findings compared outcomes for COPD patients who had triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist with patients who received one of two dual-therapy combinations. The results were presented at the American Thoracic Society’s virtual clinical trial session.

A total of 8,509 patients were randomized on a 1:1:1:1 basis to receive twice daily:

• Single-inhaler combinations of the inhaled corticosteroid (ICS) budesonide at one of two doses, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta2 agonist (LABA) formoterol.
• Dual-therapy combination glycopyrrolate and formoterol.
• Dual-therapy combination budesonide and formoterol.

The annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320 mcg and 180 mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, reported Klaus F. Rabe, MD, PhD, from LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

“Our findings show the benefits of triple therapy with a budesonide-glycopyrrolate-formoterol combination over dual therapy with a LAMA-LABA or an inhaled glucocorticoid-LABA combination with respect to the annual rate of moderate or severe COPD exacerbations, symptoms, and health-related quality of life in patients with moderate to very-severe COPD who are at risk of exacerbations,” they wrote in a study published online in the New England Journal of Medicine..

The trial showed for the first time that “triple therapy that has half the dose of steroid compared to a standard ICS/LABA combination has had greater efficacy for the exacerbation endpoint,” Dr. Rabe said during his presentation.

Triple-therapy combinations with an ICS, LAMA, and LABA are recommended for patients with COPD who remain symptomatic or experience further exacerbations on dual–ICS/LABA or –LAMA/LABA combinations. The triple combinations have been shown in several studies to lower risk of exacerbations and are associated with both better lung function and health-related quality of life, compared with dual therapies, the investigators noted.

However, concerns about adverse events associated with long-term ICS use – including pneumonia, cataracts, and increased fracture risk, possibly related to treatment duration, dose level, or type of corticosteroid used – spurred the ETHOS investigators to compare triple and dual fixed-dose combinations for efficacy and safety over 1 year.
 

Large study

They enrolled 8,509 adults aged 40-80 years with symptomatic COPD (defined as score of 10 or higher on the 40-point COPD Assessment Test). All patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

The patients were randomized in equal proportions to receive triple therapy with budesonide at 320- or 160-mcg doses plus glycopyrrolate 18 mcg, and formoterol 9.6 mcg twice daily, or to dual therapy with either glycopyrrolate plus formoterol at the same doses, or 320 mcg budesonide plus 9.6 mcg formoterol.

As noted, for the primary endpoint of the estimated annual rate of moderate or severe exacerbations, the triple combinations were associated with significantly lower rates, with a 24% lower rate (rate ratio, 0.76) with 320 mcg budesonide triple therapy, compared with glycopyrrolate-formoterol, and a 13% lower rate (RR, 0.87), compared with budesonide formoterol (P < .001 and P = .003, respectively).

The triple combination with the 160-mcg budesonide dose was associated with a 25% lower annual rate of exacerbations (RR, 0.75) vs. glycopyrrolate-formoterol, and a 14% lower rate (RR, 0.86) vs. budesonide-formoterol (P < .001 and P = .002, respectively).

Secondary efficacy endpoints also favored the triple combination, including a 20% lower rate ratio of severe exacerbations over 52 weeks for the 320-mcg budesonide group, compared with the budesonide-formoterol group (P = .02).

The 320-mcg dose combination was also associated with a 46% lower risk for all-cause mortality, compared with glycopyrrolate-formoterol (hazard ratio, 0.54; P = .0111).

Confirmed pneumonia was seen in 4.2% of patients on the 320-mcg budesonide dose, 3.5% of those in the 160-mcg group, and 4.5% of patients treated with budesonide-formoterol. The incidence of any adverse effect was similar across the treatment groups, ranging from 61.7% to 64.5%.
 

Balance exacerbation, pneumonia risk

In the question-and-answer session following his online presentation, Dr. Rabe was asked how the investigators reconciled their data showing increased incidence of pneumonia in budenoside-containing formulations with claims by the maker of the budesonide-formoterol (Symbicort, AstraZeneca) that budesonide is not associated with increased risk of pneumonia.

“We have to say that there are individuals that we have to balance the benefit of [less] exacerbation against the risk of pneumonia,” he replied, but noted that the size of the effect, observed both in ETHOS and in the KRONOS trial, was relatively small.

“This definitely adds some information for us to think about when we’re trying to do risk-benefit analysis,” commented MeiLan K. Han, MD, MS, from the University of Michigan, who moderated the session but was not involved in the study.

The ETHOS trial was funded by AstraZeneca. Dr. Rabe disclosed consulting/advisory board activity with that company and others. Dr. Han has previously disclosed consulting/advising and research funding relationships with other companies.

SOURCE: Rabe KF et al. N Engl J Med. 2020 Jun 24. doi: 10.1056/NEJMoa1916046.

Phase 3 trial findings compared outcomes for COPD patients who had triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist with patients who received one of two dual-therapy combinations. The results were presented at the American Thoracic Society’s virtual clinical trial session.

A total of 8,509 patients were randomized on a 1:1:1:1 basis to receive twice daily:

• Single-inhaler combinations of the inhaled corticosteroid (ICS) budesonide at one of two doses, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta2 agonist (LABA) formoterol.
• Dual-therapy combination glycopyrrolate and formoterol.
• Dual-therapy combination budesonide and formoterol.

The annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320 mcg and 180 mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, reported Klaus F. Rabe, MD, PhD, from LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

“Our findings show the benefits of triple therapy with a budesonide-glycopyrrolate-formoterol combination over dual therapy with a LAMA-LABA or an inhaled glucocorticoid-LABA combination with respect to the annual rate of moderate or severe COPD exacerbations, symptoms, and health-related quality of life in patients with moderate to very-severe COPD who are at risk of exacerbations,” they wrote in a study published online in the New England Journal of Medicine..

The trial showed for the first time that “triple therapy that has half the dose of steroid compared to a standard ICS/LABA combination has had greater efficacy for the exacerbation endpoint,” Dr. Rabe said during his presentation.

Triple-therapy combinations with an ICS, LAMA, and LABA are recommended for patients with COPD who remain symptomatic or experience further exacerbations on dual–ICS/LABA or –LAMA/LABA combinations. The triple combinations have been shown in several studies to lower risk of exacerbations and are associated with both better lung function and health-related quality of life, compared with dual therapies, the investigators noted.

However, concerns about adverse events associated with long-term ICS use – including pneumonia, cataracts, and increased fracture risk, possibly related to treatment duration, dose level, or type of corticosteroid used – spurred the ETHOS investigators to compare triple and dual fixed-dose combinations for efficacy and safety over 1 year.
 

Large study

They enrolled 8,509 adults aged 40-80 years with symptomatic COPD (defined as score of 10 or higher on the 40-point COPD Assessment Test). All patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

The patients were randomized in equal proportions to receive triple therapy with budesonide at 320- or 160-mcg doses plus glycopyrrolate 18 mcg, and formoterol 9.6 mcg twice daily, or to dual therapy with either glycopyrrolate plus formoterol at the same doses, or 320 mcg budesonide plus 9.6 mcg formoterol.

As noted, for the primary endpoint of the estimated annual rate of moderate or severe exacerbations, the triple combinations were associated with significantly lower rates, with a 24% lower rate (rate ratio, 0.76) with 320 mcg budesonide triple therapy, compared with glycopyrrolate-formoterol, and a 13% lower rate (RR, 0.87), compared with budesonide formoterol (P < .001 and P = .003, respectively).

The triple combination with the 160-mcg budesonide dose was associated with a 25% lower annual rate of exacerbations (RR, 0.75) vs. glycopyrrolate-formoterol, and a 14% lower rate (RR, 0.86) vs. budesonide-formoterol (P < .001 and P = .002, respectively).

Secondary efficacy endpoints also favored the triple combination, including a 20% lower rate ratio of severe exacerbations over 52 weeks for the 320-mcg budesonide group, compared with the budesonide-formoterol group (P = .02).

The 320-mcg dose combination was also associated with a 46% lower risk for all-cause mortality, compared with glycopyrrolate-formoterol (hazard ratio, 0.54; P = .0111).

Confirmed pneumonia was seen in 4.2% of patients on the 320-mcg budesonide dose, 3.5% of those in the 160-mcg group, and 4.5% of patients treated with budesonide-formoterol. The incidence of any adverse effect was similar across the treatment groups, ranging from 61.7% to 64.5%.
 

Balance exacerbation, pneumonia risk

In the question-and-answer session following his online presentation, Dr. Rabe was asked how the investigators reconciled their data showing increased incidence of pneumonia in budenoside-containing formulations with claims by the maker of the budesonide-formoterol (Symbicort, AstraZeneca) that budesonide is not associated with increased risk of pneumonia.

“We have to say that there are individuals that we have to balance the benefit of [less] exacerbation against the risk of pneumonia,” he replied, but noted that the size of the effect, observed both in ETHOS and in the KRONOS trial, was relatively small.

“This definitely adds some information for us to think about when we’re trying to do risk-benefit analysis,” commented MeiLan K. Han, MD, MS, from the University of Michigan, who moderated the session but was not involved in the study.

The ETHOS trial was funded by AstraZeneca. Dr. Rabe disclosed consulting/advisory board activity with that company and others. Dr. Han has previously disclosed consulting/advising and research funding relationships with other companies.

SOURCE: Rabe KF et al. N Engl J Med. 2020 Jun 24. doi: 10.1056/NEJMoa1916046.

Phase 3 trial findings compared outcomes for COPD patients who had triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist with patients who received one of two dual-therapy combinations. The results were presented at the American Thoracic Society’s virtual clinical trial session.

A total of 8,509 patients were randomized on a 1:1:1:1 basis to receive twice daily:

• Single-inhaler combinations of the inhaled corticosteroid (ICS) budesonide at one of two doses, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta2 agonist (LABA) formoterol.
• Dual-therapy combination glycopyrrolate and formoterol.
• Dual-therapy combination budesonide and formoterol.

The annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320 mcg and 180 mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, reported Klaus F. Rabe, MD, PhD, from LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

“Our findings show the benefits of triple therapy with a budesonide-glycopyrrolate-formoterol combination over dual therapy with a LAMA-LABA or an inhaled glucocorticoid-LABA combination with respect to the annual rate of moderate or severe COPD exacerbations, symptoms, and health-related quality of life in patients with moderate to very-severe COPD who are at risk of exacerbations,” they wrote in a study published online in the New England Journal of Medicine..

The trial showed for the first time that “triple therapy that has half the dose of steroid compared to a standard ICS/LABA combination has had greater efficacy for the exacerbation endpoint,” Dr. Rabe said during his presentation.

Triple-therapy combinations with an ICS, LAMA, and LABA are recommended for patients with COPD who remain symptomatic or experience further exacerbations on dual–ICS/LABA or –LAMA/LABA combinations. The triple combinations have been shown in several studies to lower risk of exacerbations and are associated with both better lung function and health-related quality of life, compared with dual therapies, the investigators noted.

However, concerns about adverse events associated with long-term ICS use – including pneumonia, cataracts, and increased fracture risk, possibly related to treatment duration, dose level, or type of corticosteroid used – spurred the ETHOS investigators to compare triple and dual fixed-dose combinations for efficacy and safety over 1 year.
 

Large study

They enrolled 8,509 adults aged 40-80 years with symptomatic COPD (defined as score of 10 or higher on the 40-point COPD Assessment Test). All patients were receiving at least two inhaled maintenance therapies at the time of screening, and had a postbronchodilator ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity of less than 0.7, with a postbronchodilator FEV₁ of 25%-65% of the predicted normal value. The patients all had a smoking history of at least 10 pack-years and a documented history of at least one moderate or severe COPD exacerbation in the year before screening.

The patients were randomized in equal proportions to receive triple therapy with budesonide at 320- or 160-mcg doses plus glycopyrrolate 18 mcg, and formoterol 9.6 mcg twice daily, or to dual therapy with either glycopyrrolate plus formoterol at the same doses, or 320 mcg budesonide plus 9.6 mcg formoterol.

As noted, for the primary endpoint of the estimated annual rate of moderate or severe exacerbations, the triple combinations were associated with significantly lower rates, with a 24% lower rate (rate ratio, 0.76) with 320 mcg budesonide triple therapy, compared with glycopyrrolate-formoterol, and a 13% lower rate (RR, 0.87), compared with budesonide formoterol (P < .001 and P = .003, respectively).

The triple combination with the 160-mcg budesonide dose was associated with a 25% lower annual rate of exacerbations (RR, 0.75) vs. glycopyrrolate-formoterol, and a 14% lower rate (RR, 0.86) vs. budesonide-formoterol (P < .001 and P = .002, respectively).

Secondary efficacy endpoints also favored the triple combination, including a 20% lower rate ratio of severe exacerbations over 52 weeks for the 320-mcg budesonide group, compared with the budesonide-formoterol group (P = .02).

The 320-mcg dose combination was also associated with a 46% lower risk for all-cause mortality, compared with glycopyrrolate-formoterol (hazard ratio, 0.54; P = .0111).

Confirmed pneumonia was seen in 4.2% of patients on the 320-mcg budesonide dose, 3.5% of those in the 160-mcg group, and 4.5% of patients treated with budesonide-formoterol. The incidence of any adverse effect was similar across the treatment groups, ranging from 61.7% to 64.5%.
 

Balance exacerbation, pneumonia risk

In the question-and-answer session following his online presentation, Dr. Rabe was asked how the investigators reconciled their data showing increased incidence of pneumonia in budenoside-containing formulations with claims by the maker of the budesonide-formoterol (Symbicort, AstraZeneca) that budesonide is not associated with increased risk of pneumonia.

“We have to say that there are individuals that we have to balance the benefit of [less] exacerbation against the risk of pneumonia,” he replied, but noted that the size of the effect, observed both in ETHOS and in the KRONOS trial, was relatively small.

“This definitely adds some information for us to think about when we’re trying to do risk-benefit analysis,” commented MeiLan K. Han, MD, MS, from the University of Michigan, who moderated the session but was not involved in the study.

The ETHOS trial was funded by AstraZeneca. Dr. Rabe disclosed consulting/advisory board activity with that company and others. Dr. Han has previously disclosed consulting/advising and research funding relationships with other companies.

SOURCE: Rabe KF et al. N Engl J Med. 2020 Jun 24. doi: 10.1056/NEJMoa1916046.

Immunotherapy after resection of the primary tumor improved survival in some patients with stage III melanoma in an analysis presented at the AACR virtual meeting II.

Among patients with stage IIIC disease, the 2-year survival rate was 70% in those who received immunotherapy and 59% in those who did not (P < .01). The median overall survival in this group was 32.8 months with immunotherapy and 28 months without it (P < .01).

Among patients with stage IIIA disease, the 2-year survival rate was 94% with immunotherapy and 91% without it (P = .03).

There was a trend toward a 2-year survival benefit with immunotherapy in patients with stage IIIB disease and in all 4,094 stage III patients, but the differences were not significant. The 2-year survival rate was 84% with immunotherapy and 81% without it among patients with stage IIIB disease (P = .35). The survival rates were 83% and 80%, respectively, in all stage III patients (P = .051).

This was an early analysis, noted investigator Justin Moyers, MD, of Loma Linda (Calif.) University. Ipilimumab was approved as adjuvant therapy for stage III melanoma patients in 2015, the year patients from this analysis were diagnosed.

“There’s really only 2 full years of survival data,” Dr. Moyers said. “I think given time, we will see a benefit amongst all the substages.”

In the meantime, “I would definitely not use this data to say whether or not [immunotherapy] should be given,” Dr. Moyers said.

The researchers were just using the database – which captures 52% of U.S. melanoma cases – to see if “real-world data mimics the clinical trial data,” Dr. Moyers said.

Overall, the findings support “adjuvant immunotherapy in the real-world setting,” he said.

The researchers also looked at treatment patterns in 2015-2016 across 8,160 patients with stage III melanoma, 4,094 of whom were included in the aforementioned survival analysis. There were 2,260 patients (27.7%) who received immunotherapy after surgery during that time period.

Uptake of adjuvant immunotherapy “was low to start, but those patients did better than ones who did not get” it, said AACR president Antoni Ribas, MD, PhD, of the University of California, Los Angeles, who was not involved in the study.

Immunotherapy recipients were younger, on average (54.8 years vs. 62.4 years). Patients with Charlson comorbidity scores above zero and those on Medicare were less likely to receive immunotherapy (18.4% Medicare vs. over 30% with other payers). There also were trends of decreased use with lower income and lower high school graduation rates.

The finding “highlights the negative impact of socioeconomic [factors] on access to proven therapy,” Dr. Ribas said.

As for low use among Medicare patients, uptake of new treatments, in general, “seems to be faster with private insurance,” he noted.

The study excluded patients who received systemic therapies other than immunotherapy, as well as those who received immunotherapy before surgery. Among study limitations, the specific immunotherapies patients received was unknown.

There was no external funding for this study. Dr. Moyers reported travel compensation from Astellas Pharmaceuticals in 2018. Dr. Ribas disclosed relationships with Amgen, Chugai, Merck, Sanofi, Tango, Arcus, Bioncotech, Compugen, CytomX, FLX Bio, ImaginAb, Isoplexis, Merus, Rgenix, and PACT.

[email protected]

SOURCE: Moyers J et al. AACR 2020, Abstract 4338.

Immunotherapy after resection of the primary tumor improved survival in some patients with stage III melanoma in an analysis presented at the AACR virtual meeting II.

Among patients with stage IIIC disease, the 2-year survival rate was 70% in those who received immunotherapy and 59% in those who did not (P < .01). The median overall survival in this group was 32.8 months with immunotherapy and 28 months without it (P < .01).

Among patients with stage IIIA disease, the 2-year survival rate was 94% with immunotherapy and 91% without it (P = .03).

There was a trend toward a 2-year survival benefit with immunotherapy in patients with stage IIIB disease and in all 4,094 stage III patients, but the differences were not significant. The 2-year survival rate was 84% with immunotherapy and 81% without it among patients with stage IIIB disease (P = .35). The survival rates were 83% and 80%, respectively, in all stage III patients (P = .051).

This was an early analysis, noted investigator Justin Moyers, MD, of Loma Linda (Calif.) University. Ipilimumab was approved as adjuvant therapy for stage III melanoma patients in 2015, the year patients from this analysis were diagnosed.

“There’s really only 2 full years of survival data,” Dr. Moyers said. “I think given time, we will see a benefit amongst all the substages.”

In the meantime, “I would definitely not use this data to say whether or not [immunotherapy] should be given,” Dr. Moyers said.

The researchers were just using the database – which captures 52% of U.S. melanoma cases – to see if “real-world data mimics the clinical trial data,” Dr. Moyers said.

Overall, the findings support “adjuvant immunotherapy in the real-world setting,” he said.

The researchers also looked at treatment patterns in 2015-2016 across 8,160 patients with stage III melanoma, 4,094 of whom were included in the aforementioned survival analysis. There were 2,260 patients (27.7%) who received immunotherapy after surgery during that time period.

Uptake of adjuvant immunotherapy “was low to start, but those patients did better than ones who did not get” it, said AACR president Antoni Ribas, MD, PhD, of the University of California, Los Angeles, who was not involved in the study.

Immunotherapy recipients were younger, on average (54.8 years vs. 62.4 years). Patients with Charlson comorbidity scores above zero and those on Medicare were less likely to receive immunotherapy (18.4% Medicare vs. over 30% with other payers). There also were trends of decreased use with lower income and lower high school graduation rates.

The finding “highlights the negative impact of socioeconomic [factors] on access to proven therapy,” Dr. Ribas said.

As for low use among Medicare patients, uptake of new treatments, in general, “seems to be faster with private insurance,” he noted.

The study excluded patients who received systemic therapies other than immunotherapy, as well as those who received immunotherapy before surgery. Among study limitations, the specific immunotherapies patients received was unknown.

There was no external funding for this study. Dr. Moyers reported travel compensation from Astellas Pharmaceuticals in 2018. Dr. Ribas disclosed relationships with Amgen, Chugai, Merck, Sanofi, Tango, Arcus, Bioncotech, Compugen, CytomX, FLX Bio, ImaginAb, Isoplexis, Merus, Rgenix, and PACT.

[email protected]

SOURCE: Moyers J et al. AACR 2020, Abstract 4338.

Immunotherapy after resection of the primary tumor improved survival in some patients with stage III melanoma in an analysis presented at the AACR virtual meeting II.

Among patients with stage IIIC disease, the 2-year survival rate was 70% in those who received immunotherapy and 59% in those who did not (P < .01). The median overall survival in this group was 32.8 months with immunotherapy and 28 months without it (P < .01).

Among patients with stage IIIA disease, the 2-year survival rate was 94% with immunotherapy and 91% without it (P = .03).

There was a trend toward a 2-year survival benefit with immunotherapy in patients with stage IIIB disease and in all 4,094 stage III patients, but the differences were not significant. The 2-year survival rate was 84% with immunotherapy and 81% without it among patients with stage IIIB disease (P = .35). The survival rates were 83% and 80%, respectively, in all stage III patients (P = .051).

This was an early analysis, noted investigator Justin Moyers, MD, of Loma Linda (Calif.) University. Ipilimumab was approved as adjuvant therapy for stage III melanoma patients in 2015, the year patients from this analysis were diagnosed.

“There’s really only 2 full years of survival data,” Dr. Moyers said. “I think given time, we will see a benefit amongst all the substages.”

In the meantime, “I would definitely not use this data to say whether or not [immunotherapy] should be given,” Dr. Moyers said.

The researchers were just using the database – which captures 52% of U.S. melanoma cases – to see if “real-world data mimics the clinical trial data,” Dr. Moyers said.

Overall, the findings support “adjuvant immunotherapy in the real-world setting,” he said.

The researchers also looked at treatment patterns in 2015-2016 across 8,160 patients with stage III melanoma, 4,094 of whom were included in the aforementioned survival analysis. There were 2,260 patients (27.7%) who received immunotherapy after surgery during that time period.

Uptake of adjuvant immunotherapy “was low to start, but those patients did better than ones who did not get” it, said AACR president Antoni Ribas, MD, PhD, of the University of California, Los Angeles, who was not involved in the study.

Immunotherapy recipients were younger, on average (54.8 years vs. 62.4 years). Patients with Charlson comorbidity scores above zero and those on Medicare were less likely to receive immunotherapy (18.4% Medicare vs. over 30% with other payers). There also were trends of decreased use with lower income and lower high school graduation rates.

The finding “highlights the negative impact of socioeconomic [factors] on access to proven therapy,” Dr. Ribas said.

As for low use among Medicare patients, uptake of new treatments, in general, “seems to be faster with private insurance,” he noted.

The study excluded patients who received systemic therapies other than immunotherapy, as well as those who received immunotherapy before surgery. Among study limitations, the specific immunotherapies patients received was unknown.

There was no external funding for this study. Dr. Moyers reported travel compensation from Astellas Pharmaceuticals in 2018. Dr. Ribas disclosed relationships with Amgen, Chugai, Merck, Sanofi, Tango, Arcus, Bioncotech, Compugen, CytomX, FLX Bio, ImaginAb, Isoplexis, Merus, Rgenix, and PACT.

[email protected]

SOURCE: Moyers J et al. AACR 2020, Abstract 4338.

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.