Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.

These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.

These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).

Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.

Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.

Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.

These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.

“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.

The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.

Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.

This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.

Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.

Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.

The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.

“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.

However, she expressed concern that “with the telehealth visits, we can create some disparities.”

“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.

Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”

Impact on lung cancer clinical trials

The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.

Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.

The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).

The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.

The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).

Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).

Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).

“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.

Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.

This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).

Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).

The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.

Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.

The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.

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

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

ON101 (Fespixon, Oneness Biotech), a first-in-class, macrophage-regulating, wound-healing cream for diabetic foot ulcers has shown benefit over absorbent dressings in a phase 3 trial, with another trial ongoing.

The product became available in Taiwan on July 4, 2021, after receiving regulatory approval from the Taiwan Food and Drug Administration based on efficacy and safety findings in a three-country phase 3 clinical trial.  

Oneness Biotech has also just started a second phase 3 trial in the United States, with a planned enrollment of 208 patients with diabetic foot ulcers, which will compare ON101 cream versus placebo cream, in addition to standard care, over 20 weeks.

The company expects to complete that trial and file a new drug application with the U.S. Food and Drug Administration in 2023, and a global launch is planned for 2025, said Oneness Biotech founder and CEO William Lu.
 

Current and upcoming trials

The Taiwan FDA approval of ON101 was based on a 236-patient clinical trial conducted in Taiwan, China, and the United States by Yu-Yao Huang MD, PhD, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, and colleagues, which was published online Sept. 3, 2021, in JAMA Network Open.

The study results will also be presented during an oral session at the European Association for the Study of Diabetes meeting on Sept. 30.

The published trial showed that foot ulcers treated with ON101 cream were almost three times more likely to be completely healed at 16 weeks than those treated with standard care with an absorbent dressing (Aquacel Hydrofiber, ConvaTec) (odds ratio, 2.84; P < .001).

“The findings of this study suggest that ON101, a macrophage regulator that behaves differently from moisture-retaining dressings, represents an active-healing alternative for home and primary care of patients with chronic [diabetic foot ulcers],” the researchers concluded.

“ON101 was also granted a fast track designation by the U.S. FDA in March this year,” senior author Shun-Chen Chang, MD, Taipei Medical University–Shuang Ho Hospital, New Taipei City, Taiwan, said in an interview.

“Patients in the United States can access this new drug via the expanded access program or by participating in the second phase 3 trial in the United States,” added coauthor Shawn M. Cazzell, DPM, chief medical officer, Limb Preservation Platform, Fresno, Calif., who is involved with both trials.

It is “exciting” to have a new therapy for diabetic foot ulcers, said Dr. Cazzell, because they are serious and life-threatening.
 

Could cream with plant extracts surpass current care?

Current standard clinical care for diabetic foot ulcer consists of debridement, off-loading, infection control, and maintaining a moist environment with dressings, Huang and colleagues explain. If the foot ulcer does not respond, growth factors, tissue-engineering products, hyperbaric oxygen, or negative pressure wound therapies may be used.

However, the number of amputations from chronic diabetic foot ulcers that do not heal is increasing, pointing to a need for better treatment options.  

Hyperglycemia increases the ratio of M1 proinflammatory macrophages to M2 proregenerative macrophages, and accumulating evidence suggests this might be a potential treatment target.  

Researchers at Oneness Biotech showed that ON101, which is comprised of extracts from two plants, Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages.

An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis.

In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model. This was followed by promising efficacy and safety results in two trials of 24 patients and 30 patients.
 

Significantly better healing with ON101 than standard care

For the current phase 3, randomized clinical trial, researchers enrolled patients in 21 clinics from November 2012 to May 2020.

To be eligible for the study, patients had to be 20-80 years old, with a hemoglobin A1c less than 12%. They also had to have a Wagner grade 1 or 2 foot ulcer that was 1-25 cm² after debridement, had been treated with standard care, and was present for at least 4 weeks.

Patients were a mean age of 57 years and 74% were men. They had a mean A1c of 8.1%, and 61% had had diabetes for more than 10 years.

Most (78%) of the diabetic foot ulcers were Wagner grade 2. The wounds had a mean area of 4.8 cm² and had been present for a mean of 7 months.

Patients were instructed on how to self-administer ON101 cream twice a day (treatment group, n = 122) or how to apply an absorbent dressing and change it daily or two or three times a week (standard care group, n = 114). All patients were allowed to apply a sterile gauze dressing.  

They visited the clinic every 2 weeks during the 16-week treatment phase and 12-week observation phase.

In the full analysis set, 74 patients (61%) in the ON101 group and 40 patients (35%) in the standard care group had complete wound healing after 16 weeks of treatment.

The subgroup of patients at higher risk of poor wound healing (A1c >9%, ulcer area >5 cm², and diabetic foot ulcer duration >6 months) also had significantly better healing with the ON101 cream than standard care.

There were seven (5.7%) treatment-emergent adverse events in the ON101 group versus five (4.4%) in the standard care group.

There were no treatment-related serious adverse events in the ON101 group versus one (0.9%) in the comparator group.

The study was funded by Oneness Biotech, Microbio Group, and Shanghai Haihe Pharmaceutical. One author has reported receiving fees from Oneness Biotech, and Dr. Chang has reported receiving a speakers fee from Oneness Biotech. The other authors reported no relevant financial relationships.

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

Air pollution is the second-leading cause of lung cancer in the world, after smoking, results of a novel analysis suggest. The researchers call for concerted action.

Ja&#039;Crispy/iStock/Getty Images Plus

The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.

“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.

“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.

Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.

She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.

The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.

It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.

Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.

A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.

Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.

Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.

Hopefully, that benefit will also be seen regarding other diseases, he added.

The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.

“It is time to join forces,” he added, “to ‘clean the air.’ ”

Dr. Berg’s presentation was warmly received on social media.

It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.

“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.

It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
 

Contribution of air pollution to lung cancer

In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”

Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.

A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.

Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.

The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.

She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.

It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.

Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.

Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.

The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.

In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.

At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m³. Both of these rates are far below those seen in more severely affected countries.

“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”

No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.

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

Air pollution is the second-leading cause of lung cancer in the world, after smoking, results of a novel analysis suggest. The researchers call for concerted action.

Ja&#039;Crispy/iStock/Getty Images Plus

The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.

“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.

“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.

Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.

She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.

The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.

It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.

Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.

A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.

Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.

Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.

Hopefully, that benefit will also be seen regarding other diseases, he added.

The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.

“It is time to join forces,” he added, “to ‘clean the air.’ ”

Dr. Berg’s presentation was warmly received on social media.

It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.

“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.

It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
 

Contribution of air pollution to lung cancer

In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”

Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.

A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.

Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.

The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.

She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.

It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.

Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.

Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.

The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.

In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.

At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m³. Both of these rates are far below those seen in more severely affected countries.

“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”

No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.

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

Air pollution is the second-leading cause of lung cancer in the world, after smoking, results of a novel analysis suggest. The researchers call for concerted action.

Ja&#039;Crispy/iStock/Getty Images Plus

The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.

“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.

“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.

Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.

She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.

The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.

It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.

Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.

A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.

Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.

Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.

Hopefully, that benefit will also be seen regarding other diseases, he added.

The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.

“It is time to join forces,” he added, “to ‘clean the air.’ ”

Dr. Berg’s presentation was warmly received on social media.

It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.

“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.

It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
 

Contribution of air pollution to lung cancer

In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”

Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.

A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.

Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.

The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.

She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.

It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.

Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.

Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.

The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.

In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.

At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m³. Both of these rates are far below those seen in more severely affected countries.

“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”

No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

Virtual care (VC) has emerged as an effective mode of health care delivery especially in settings where significant barriers to traditional in-person visits exist; a large systematic review supports feasibility of telemedicine in primary care and suggests that telemedicine is at least as effective as traditional care.¹ Nevertheless, broad adoption of VC into practice has lagged, impeded by government and private insurance reimbursement requirements as well as the persistent belief that care can best be delivered in person.^2-4 Before the COVID-19 pandemic, states that enacted parity legislation that required private insurance companies to provide reimbursement coverage for telehealth services saw a significant increase in the number of outpatient telehealth visits (about ≥ 30% odds compared with nonparity states).³

With the onset of the COVID-19 pandemic, in-person medical appointments were converted to VC visits to reduce increased exposure risks to patients and health care workers.⁵ Prior government and private sector policies were suspended, and payment restrictions lifted, enabling adoption of VC modalities to rapidly accommodate the emergent need and Centers for Disease Control and Prevention (CDC) recommendations for virtual care.^6-11

The CDC guidelines on managing operations during the COVID-19 pandemic highlighted the need to provide care in the safest way for patients and health care personnel and emphasized the importance of optimizing telehealth services. The federal government facilitated telehealth during the COVID-19 pandemic via temporary measures under the COVID-19 public health emergency declaration. This included Health Insurance Portability and Accountability Act flexibility to use everyday technology for VC visits, regulatory changes to deliver services to Medicare and Medicaid patients, permission of telehealth services across state lines, and prescribing of controlled substances via telehealth without an in-person medical evaluation.⁷

In response, health care providers (HCPs) and health care organizations created or expanded on existing telehealth infrastructure, developing virtual urgent care centers and telephone-based programs to evaluate patients remotely via screening questions that triaged them to a correct level of response, with possible subsequent virtual physician evaluation if indicated.^12,13

The Veterans Health Administration (VHA) also shifted to a VC model in response to COVID-19 guided by a unique perspective from a well-developed prior VC experience.^14-16 As a federally funded system, the VHA depends on workload documentation for budgeting. Since 2015, the VHA has provided workload credit and incentivized HCPs (via pay for performance) for the use of VC, including telephone visits, video visits, and secure messaging. These incentives resulted in higher rates of telehealth utilization before the COVID-19 pandemic compared with the private sector (with 4.2% and 0.7% of visits within the VHA being telephone and video visits, respectively, compared with telehealth utilization rates of 1.0% for Medicare recipients and 1.1% in an all-payer database).¹⁶

Historically, VHA care has successfully transitioned from in-person care models to exclusively virtual modalities to prevent suspension of medical services during natural disasters. Studies performed during these periods, specifically during the 2017 hurricane season (during which multiple VHA hospitals were closed or had limited in-person service available), supported telehealth as an efficient health care delivery method, and even recommended expanding telehealth services within non-VHA environments to accommodate needs of the general public during crises and postdisaster health care delivery.¹⁷

Armed with both a well-established telehealth infrastructure and prior knowledge gained from successful systemwide implementation of virtual care during times of disaster, US Department of Veterans Affairs (VA) Connecticut Healthcare System (VACHS) primary care quickly transitioned to a VC model in response to COVID-19.¹⁶ Early in the pandemic, a rapid transition to virtual care (RTVC) model was developed, including implementation of virtual respiratory urgent clinics (VRUCs), defined as virtual respiratory symptom triage clinics, staffed by primary care providers (PCPs) aimed at minimizing patient and health care worker exposure risk.

Methods

VACHS consists of 8 primary care sites, including a major tertiary care center, a smaller medical center with full ambulatory services, and 6 community-based outpatient clinics with only primary care and mental health. There are 80 individual PCPs delivering care to 58,058 veterans. VRUCs were established during the COVID-19 pandemic to cover patients across the entire health care system, using a rotational schedule of VA PCPs.

COVID-19 Urgent Clinics Program

Within the first few weeks of the pandemic, VACHS primary care established VRUCS to provide expeditious virtual assessment of respiratory or flu-like symptoms. Using the established telehealth system, the intervention aimed to provide emergent screening, testing, and care to those with potential COVID-19 infections. The model also was designed to minimize exposures to the health care workforce and patients.

Retrospective analysis was performed using information obtained from the electronic health record (EHR) database to describe the characteristics of patients who received care through the VRUCs, such as demographics, era of military service, COVID-19 testing rates and results, as well as subsequent emergency department (ED) visits and hospital admissions. A secondary aim included collection of additional qualitative data via a random sample chart review.

Virtual clinics were established January 22, 2020, and data were analyzed over the next 3 months. Data were retrieved and analyzed from the EHR, and codes were used to categorize the VRUCs.

Results

A total of 445 unique patients used these clinics during this period. Unique patients were defined as individual patients (some may have used a clinic more than once but were counted only once). Of this group, 82% were male, and 48% served in the Gulf War era (1990 to present). A total of 51% of patients received a COVID-19 test (clinics began before wide testing availability), and 10% tested positive. Of all patients using the clinics, approximately 5% were admitted to the hospital, and 18% had at least 1 subsequent ED visit (Table).

A secondary aim included review of a random sample of 99 patient charts to gain additional information regarding whether the patient was given appropriate isolation precautions, was in a high-exposure occupation (eg, could expose a large number of people), and whether there was appropriate documentation of goals of care, health care proxy or referral to social work to discuss advance directives. In addition, we calculated the average length of time between patients’ initial contact with the health care system call center and the return call by the PCP (wait time).Of charts reviewed, the majority (71%) had documentation of appropriate isolation precautions. Although 25% of patients had documentation of a high-risk profession with potential to expose many people, more than half of the patients had no documentation of occupation. Most patients (86%) had no updated documentation regarding goals of care, health care proxy, or advance directives in their urgent care VC visit. The average time between the patient initiating contact with the health care system call center and a return call to the patient from a PCP was 104 minutes (excluding calls received after 3:30 pm).

Discussion

This analysis adds to the growing literature on use of VC during the COVID-19 pandemic. Specifically, we describe the population of patients who used VRUCs within a large health care system in a RTVC. This analysis was limited by lack of available testing during the initial phase of the pandemic, which contributed to the lower than expected rates of testing and test positivity in patients managed via VRUCs. In addition, chart review data are limited as the data includes only what was documented during the visit and not the entire discussion during the encounter.

Several important outcomes from this analysis can be applied to interventions in the future, which may have large public health implications: Several hundred patients who reported respiratory symptoms were expeditiously evaluated by a PCP using VC. The average wait time to full clinical assessment was about 1.5 hours. This short duration between contact and evaluation permitted early education about isolation precautions, which may have minimized spread. In addition, this innovation kept patients out of the medical center, eliminating chains of transmission to other vulnerable patients and health care workers.

Our retrospective chart review also revealed that more than half the patients were not queried about their occupation, but of those that were asked, a significant number were in high-risk professions potentially exposing large numbers of people. This would be an important aspect to add to future templated notes to minimize work-related exposures. Also, we identified that few HCPs discussed goals of care with patients. Given the nature of COVID-19 and potential for rapid decompensation especially in vulnerable patients, this also would be important to include in the future.

Conclusions

VC urgent care clinics to address possible COVID-19 symptoms facilitated expeditious PCP assessment while keeping potentially contagious patients outside of high-risk health care environments. Streamlining and optimizing clinical VC assessments will be imperative to future management of COVID-19 and potentially to other future infectious pandemics. This includes development of templated notes incorporating counseling regarding appropriate isolation, questions about high-contact occupations, and goals of care discussions.

Acknowledgment

The authors thank Robert F. Walsh, MHA.

Virtual care (VC) has emerged as an effective mode of health care delivery especially in settings where significant barriers to traditional in-person visits exist; a large systematic review supports feasibility of telemedicine in primary care and suggests that telemedicine is at least as effective as traditional care.¹ Nevertheless, broad adoption of VC into practice has lagged, impeded by government and private insurance reimbursement requirements as well as the persistent belief that care can best be delivered in person.^2-4 Before the COVID-19 pandemic, states that enacted parity legislation that required private insurance companies to provide reimbursement coverage for telehealth services saw a significant increase in the number of outpatient telehealth visits (about ≥ 30% odds compared with nonparity states).³

With the onset of the COVID-19 pandemic, in-person medical appointments were converted to VC visits to reduce increased exposure risks to patients and health care workers.⁵ Prior government and private sector policies were suspended, and payment restrictions lifted, enabling adoption of VC modalities to rapidly accommodate the emergent need and Centers for Disease Control and Prevention (CDC) recommendations for virtual care.^6-11

The CDC guidelines on managing operations during the COVID-19 pandemic highlighted the need to provide care in the safest way for patients and health care personnel and emphasized the importance of optimizing telehealth services. The federal government facilitated telehealth during the COVID-19 pandemic via temporary measures under the COVID-19 public health emergency declaration. This included Health Insurance Portability and Accountability Act flexibility to use everyday technology for VC visits, regulatory changes to deliver services to Medicare and Medicaid patients, permission of telehealth services across state lines, and prescribing of controlled substances via telehealth without an in-person medical evaluation.⁷

In response, health care providers (HCPs) and health care organizations created or expanded on existing telehealth infrastructure, developing virtual urgent care centers and telephone-based programs to evaluate patients remotely via screening questions that triaged them to a correct level of response, with possible subsequent virtual physician evaluation if indicated.^12,13

The Veterans Health Administration (VHA) also shifted to a VC model in response to COVID-19 guided by a unique perspective from a well-developed prior VC experience.^14-16 As a federally funded system, the VHA depends on workload documentation for budgeting. Since 2015, the VHA has provided workload credit and incentivized HCPs (via pay for performance) for the use of VC, including telephone visits, video visits, and secure messaging. These incentives resulted in higher rates of telehealth utilization before the COVID-19 pandemic compared with the private sector (with 4.2% and 0.7% of visits within the VHA being telephone and video visits, respectively, compared with telehealth utilization rates of 1.0% for Medicare recipients and 1.1% in an all-payer database).¹⁶

Historically, VHA care has successfully transitioned from in-person care models to exclusively virtual modalities to prevent suspension of medical services during natural disasters. Studies performed during these periods, specifically during the 2017 hurricane season (during which multiple VHA hospitals were closed or had limited in-person service available), supported telehealth as an efficient health care delivery method, and even recommended expanding telehealth services within non-VHA environments to accommodate needs of the general public during crises and postdisaster health care delivery.¹⁷

Armed with both a well-established telehealth infrastructure and prior knowledge gained from successful systemwide implementation of virtual care during times of disaster, US Department of Veterans Affairs (VA) Connecticut Healthcare System (VACHS) primary care quickly transitioned to a VC model in response to COVID-19.¹⁶ Early in the pandemic, a rapid transition to virtual care (RTVC) model was developed, including implementation of virtual respiratory urgent clinics (VRUCs), defined as virtual respiratory symptom triage clinics, staffed by primary care providers (PCPs) aimed at minimizing patient and health care worker exposure risk.

Methods

VACHS consists of 8 primary care sites, including a major tertiary care center, a smaller medical center with full ambulatory services, and 6 community-based outpatient clinics with only primary care and mental health. There are 80 individual PCPs delivering care to 58,058 veterans. VRUCs were established during the COVID-19 pandemic to cover patients across the entire health care system, using a rotational schedule of VA PCPs.

COVID-19 Urgent Clinics Program

Within the first few weeks of the pandemic, VACHS primary care established VRUCS to provide expeditious virtual assessment of respiratory or flu-like symptoms. Using the established telehealth system, the intervention aimed to provide emergent screening, testing, and care to those with potential COVID-19 infections. The model also was designed to minimize exposures to the health care workforce and patients.

Retrospective analysis was performed using information obtained from the electronic health record (EHR) database to describe the characteristics of patients who received care through the VRUCs, such as demographics, era of military service, COVID-19 testing rates and results, as well as subsequent emergency department (ED) visits and hospital admissions. A secondary aim included collection of additional qualitative data via a random sample chart review.

Virtual clinics were established January 22, 2020, and data were analyzed over the next 3 months. Data were retrieved and analyzed from the EHR, and codes were used to categorize the VRUCs.

Results

A total of 445 unique patients used these clinics during this period. Unique patients were defined as individual patients (some may have used a clinic more than once but were counted only once). Of this group, 82% were male, and 48% served in the Gulf War era (1990 to present). A total of 51% of patients received a COVID-19 test (clinics began before wide testing availability), and 10% tested positive. Of all patients using the clinics, approximately 5% were admitted to the hospital, and 18% had at least 1 subsequent ED visit (Table).

A secondary aim included review of a random sample of 99 patient charts to gain additional information regarding whether the patient was given appropriate isolation precautions, was in a high-exposure occupation (eg, could expose a large number of people), and whether there was appropriate documentation of goals of care, health care proxy or referral to social work to discuss advance directives. In addition, we calculated the average length of time between patients’ initial contact with the health care system call center and the return call by the PCP (wait time).Of charts reviewed, the majority (71%) had documentation of appropriate isolation precautions. Although 25% of patients had documentation of a high-risk profession with potential to expose many people, more than half of the patients had no documentation of occupation. Most patients (86%) had no updated documentation regarding goals of care, health care proxy, or advance directives in their urgent care VC visit. The average time between the patient initiating contact with the health care system call center and a return call to the patient from a PCP was 104 minutes (excluding calls received after 3:30 pm).

Discussion

This analysis adds to the growing literature on use of VC during the COVID-19 pandemic. Specifically, we describe the population of patients who used VRUCs within a large health care system in a RTVC. This analysis was limited by lack of available testing during the initial phase of the pandemic, which contributed to the lower than expected rates of testing and test positivity in patients managed via VRUCs. In addition, chart review data are limited as the data includes only what was documented during the visit and not the entire discussion during the encounter.

Several important outcomes from this analysis can be applied to interventions in the future, which may have large public health implications: Several hundred patients who reported respiratory symptoms were expeditiously evaluated by a PCP using VC. The average wait time to full clinical assessment was about 1.5 hours. This short duration between contact and evaluation permitted early education about isolation precautions, which may have minimized spread. In addition, this innovation kept patients out of the medical center, eliminating chains of transmission to other vulnerable patients and health care workers.

Our retrospective chart review also revealed that more than half the patients were not queried about their occupation, but of those that were asked, a significant number were in high-risk professions potentially exposing large numbers of people. This would be an important aspect to add to future templated notes to minimize work-related exposures. Also, we identified that few HCPs discussed goals of care with patients. Given the nature of COVID-19 and potential for rapid decompensation especially in vulnerable patients, this also would be important to include in the future.

Conclusions

VC urgent care clinics to address possible COVID-19 symptoms facilitated expeditious PCP assessment while keeping potentially contagious patients outside of high-risk health care environments. Streamlining and optimizing clinical VC assessments will be imperative to future management of COVID-19 and potentially to other future infectious pandemics. This includes development of templated notes incorporating counseling regarding appropriate isolation, questions about high-contact occupations, and goals of care discussions.

Acknowledgment

The authors thank Robert F. Walsh, MHA.

Virtual care (VC) has emerged as an effective mode of health care delivery especially in settings where significant barriers to traditional in-person visits exist; a large systematic review supports feasibility of telemedicine in primary care and suggests that telemedicine is at least as effective as traditional care.¹ Nevertheless, broad adoption of VC into practice has lagged, impeded by government and private insurance reimbursement requirements as well as the persistent belief that care can best be delivered in person.^2-4 Before the COVID-19 pandemic, states that enacted parity legislation that required private insurance companies to provide reimbursement coverage for telehealth services saw a significant increase in the number of outpatient telehealth visits (about ≥ 30% odds compared with nonparity states).³

With the onset of the COVID-19 pandemic, in-person medical appointments were converted to VC visits to reduce increased exposure risks to patients and health care workers.⁵ Prior government and private sector policies were suspended, and payment restrictions lifted, enabling adoption of VC modalities to rapidly accommodate the emergent need and Centers for Disease Control and Prevention (CDC) recommendations for virtual care.^6-11

The CDC guidelines on managing operations during the COVID-19 pandemic highlighted the need to provide care in the safest way for patients and health care personnel and emphasized the importance of optimizing telehealth services. The federal government facilitated telehealth during the COVID-19 pandemic via temporary measures under the COVID-19 public health emergency declaration. This included Health Insurance Portability and Accountability Act flexibility to use everyday technology for VC visits, regulatory changes to deliver services to Medicare and Medicaid patients, permission of telehealth services across state lines, and prescribing of controlled substances via telehealth without an in-person medical evaluation.⁷

In response, health care providers (HCPs) and health care organizations created or expanded on existing telehealth infrastructure, developing virtual urgent care centers and telephone-based programs to evaluate patients remotely via screening questions that triaged them to a correct level of response, with possible subsequent virtual physician evaluation if indicated.^12,13

The Veterans Health Administration (VHA) also shifted to a VC model in response to COVID-19 guided by a unique perspective from a well-developed prior VC experience.^14-16 As a federally funded system, the VHA depends on workload documentation for budgeting. Since 2015, the VHA has provided workload credit and incentivized HCPs (via pay for performance) for the use of VC, including telephone visits, video visits, and secure messaging. These incentives resulted in higher rates of telehealth utilization before the COVID-19 pandemic compared with the private sector (with 4.2% and 0.7% of visits within the VHA being telephone and video visits, respectively, compared with telehealth utilization rates of 1.0% for Medicare recipients and 1.1% in an all-payer database).¹⁶

Historically, VHA care has successfully transitioned from in-person care models to exclusively virtual modalities to prevent suspension of medical services during natural disasters. Studies performed during these periods, specifically during the 2017 hurricane season (during which multiple VHA hospitals were closed or had limited in-person service available), supported telehealth as an efficient health care delivery method, and even recommended expanding telehealth services within non-VHA environments to accommodate needs of the general public during crises and postdisaster health care delivery.¹⁷

Armed with both a well-established telehealth infrastructure and prior knowledge gained from successful systemwide implementation of virtual care during times of disaster, US Department of Veterans Affairs (VA) Connecticut Healthcare System (VACHS) primary care quickly transitioned to a VC model in response to COVID-19.¹⁶ Early in the pandemic, a rapid transition to virtual care (RTVC) model was developed, including implementation of virtual respiratory urgent clinics (VRUCs), defined as virtual respiratory symptom triage clinics, staffed by primary care providers (PCPs) aimed at minimizing patient and health care worker exposure risk.

Methods

VACHS consists of 8 primary care sites, including a major tertiary care center, a smaller medical center with full ambulatory services, and 6 community-based outpatient clinics with only primary care and mental health. There are 80 individual PCPs delivering care to 58,058 veterans. VRUCs were established during the COVID-19 pandemic to cover patients across the entire health care system, using a rotational schedule of VA PCPs.

COVID-19 Urgent Clinics Program

Within the first few weeks of the pandemic, VACHS primary care established VRUCS to provide expeditious virtual assessment of respiratory or flu-like symptoms. Using the established telehealth system, the intervention aimed to provide emergent screening, testing, and care to those with potential COVID-19 infections. The model also was designed to minimize exposures to the health care workforce and patients.

Retrospective analysis was performed using information obtained from the electronic health record (EHR) database to describe the characteristics of patients who received care through the VRUCs, such as demographics, era of military service, COVID-19 testing rates and results, as well as subsequent emergency department (ED) visits and hospital admissions. A secondary aim included collection of additional qualitative data via a random sample chart review.

Virtual clinics were established January 22, 2020, and data were analyzed over the next 3 months. Data were retrieved and analyzed from the EHR, and codes were used to categorize the VRUCs.

Results

A total of 445 unique patients used these clinics during this period. Unique patients were defined as individual patients (some may have used a clinic more than once but were counted only once). Of this group, 82% were male, and 48% served in the Gulf War era (1990 to present). A total of 51% of patients received a COVID-19 test (clinics began before wide testing availability), and 10% tested positive. Of all patients using the clinics, approximately 5% were admitted to the hospital, and 18% had at least 1 subsequent ED visit (Table).

A secondary aim included review of a random sample of 99 patient charts to gain additional information regarding whether the patient was given appropriate isolation precautions, was in a high-exposure occupation (eg, could expose a large number of people), and whether there was appropriate documentation of goals of care, health care proxy or referral to social work to discuss advance directives. In addition, we calculated the average length of time between patients’ initial contact with the health care system call center and the return call by the PCP (wait time).Of charts reviewed, the majority (71%) had documentation of appropriate isolation precautions. Although 25% of patients had documentation of a high-risk profession with potential to expose many people, more than half of the patients had no documentation of occupation. Most patients (86%) had no updated documentation regarding goals of care, health care proxy, or advance directives in their urgent care VC visit. The average time between the patient initiating contact with the health care system call center and a return call to the patient from a PCP was 104 minutes (excluding calls received after 3:30 pm).

Discussion

This analysis adds to the growing literature on use of VC during the COVID-19 pandemic. Specifically, we describe the population of patients who used VRUCs within a large health care system in a RTVC. This analysis was limited by lack of available testing during the initial phase of the pandemic, which contributed to the lower than expected rates of testing and test positivity in patients managed via VRUCs. In addition, chart review data are limited as the data includes only what was documented during the visit and not the entire discussion during the encounter.

Several important outcomes from this analysis can be applied to interventions in the future, which may have large public health implications: Several hundred patients who reported respiratory symptoms were expeditiously evaluated by a PCP using VC. The average wait time to full clinical assessment was about 1.5 hours. This short duration between contact and evaluation permitted early education about isolation precautions, which may have minimized spread. In addition, this innovation kept patients out of the medical center, eliminating chains of transmission to other vulnerable patients and health care workers.

Our retrospective chart review also revealed that more than half the patients were not queried about their occupation, but of those that were asked, a significant number were in high-risk professions potentially exposing large numbers of people. This would be an important aspect to add to future templated notes to minimize work-related exposures. Also, we identified that few HCPs discussed goals of care with patients. Given the nature of COVID-19 and potential for rapid decompensation especially in vulnerable patients, this also would be important to include in the future.

Conclusions

VC urgent care clinics to address possible COVID-19 symptoms facilitated expeditious PCP assessment while keeping potentially contagious patients outside of high-risk health care environments. Streamlining and optimizing clinical VC assessments will be imperative to future management of COVID-19 and potentially to other future infectious pandemics. This includes development of templated notes incorporating counseling regarding appropriate isolation, questions about high-contact occupations, and goals of care discussions.

Acknowledgment

The authors thank Robert F. Walsh, MHA.

The Veterans Health Administration (VHA) clinical practice recommendations endorse a power mobility device (PMD) for individuals with adequate judgment, cognitive ability, and vision who are unable to propel a manual wheelchair or walk community distances despite standard medical and rehabilitative interventions.¹ VHA supports the use of a PMD in order to access medical care and accomplish activities of daily living, both at home and in the community for veterans with mobility limitations secondary to cardiovascular disease, neurologic disorders, pulmonary disease, or musculoskeletal disorders. The goal of a PMD use is increased participation in community and social life, improved health maintenance via enhanced access to medical facilities, and an overall enhanced quality of life. However, there is a common concern among health care providers that prescribing a PMD may decrease physical activity, in turn, leading to obesity and increasing morbidity. ²

The prevalence of obesity is increasing in the United States. In the past decade 35.0% of men and 36.8% of women were classified as obese (body mass index [BMI], ≥ 30).³ Recent figures from the Centers for Disease Control and Prevention estimate that the overall prevalence of obesity in Americans is closer to 42.4%.⁴ The veteran population is not immune to this; a 2014 study of nearly 5 million veterans reported that the prevalence of obesity in this population was 41%.^5,6 In addition to obesity being implicated in exacerbating many medical problems, such as osteoarthritis, insulin resistance, and heart disease, obesity also is associated with a significant decrease in lifespan.⁷ Almost half of adults who report ambulatory dysfunction are obese.⁸ Given the increased morbidity and mortality as a result of obesity, interventions that may promote weight gain need to be appropriately identified and minimized.

Methods

The institutional review board at Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia, reviewed and approved this study. A waiver of participant consent was approved due to the nature of the research (medical records of patients, some of whom were deceased) and the type of data collected (retrospective data). In addition, each individual was assigned a sequential code to de-identify any personal information. Prosthetics department medical records of consecutive veterans who received PMDs for the first time between January 1, 2011 and June 30, 2012, were reviewed.

Data extracted from the electronic health record (EHR) included demographics, indication for power mobility, weight at time of PMD prescription, weight at 2-years postprescription, and height. Weight readings were considered valid if weight was taken within 3 months of initial prescription and then again within 3 months at the 2-year interval. Individuals without weights recorded in these time frames were excluded. In addition, we excluded medical conditions that might significantly affect body weight, including amyotrophic lateral sclerosis (ALS), amputation during the study period, or history of weight loss surgery. Cancer diagnoses were excluded as they were not an indication for power mobility in the VHA. ALS, though variable in its disease course, was specifically excluded given the likelihood of these patients dying of the natural progression of the disease before the 2-year follow-up period: Median survival times in patients diagnosed with ALS aged > 60 years was < 15 months. ^10-12

The EHRs of 399 individuals who received a PMD during the period were reviewed, and 185 veterans met criteria for data analysis. Subject exclusions in the weight and BMI analysis included death during the follow-up period (89), missing data (68), prior PMD users who came in for replacements (53), and ALS (4) (Figure 1). Patients were not excluded based on the presence or absence of intentional weight loss efforts as this information was not readily available through chart review.

Statistical Analysis

The primary outcome measure was the change in BMI and body weight from time 1 (date of PMD prescription) to time 2 (2 years later). Analyses were performed using IBM SPSS Statistics, Version 21. BMI was calculated using the weight (lb) x 703/ (height [inches]).² Dichotomization of BMI was performed using the conventional cut scores: < 30.0, not obese; and ≥ 30.0, obese. Paired t tests and SPSS general linear model (repeated measures) were used to examine change of BMI from time 1 to time 2. The exact McNemar test was used to examine change in obesity classification across time 1 and time 2. Correlating with Yang’s retrospective observational study, data were analyzed separately for aged < 65 years and aged≥ 65 years.²

Results

Of the 185 veterans, 181 were male (98%); mean age was 67.3 years (range, 26-90); and 55% were aged ≥ 65 years. Musculoskeletal disorders (41.6%) were the most common primary indication for a PMD, followed by pulmonary disorders (25.4%) and cardiovascular disorders (23.8%) (Table 1).

There was a significant decrease in BMI in the first 2 years after receiving a PMD prescription for the first time (estimated marginal means: 31.5 to 30.9 , P = .02). However, age moderated the relationship between BMI and time F[1, 183] = 12.14, P = .001, partial η² = .06 (Table 2). The 101 subjects aged > 65 years experienced a significant decrease in BMI (estimated marginal means: 30.3 to 29.1, P < .001), whereas the 84 patients aged < 65 years experienced a slight and nonsignificant increase in BMI (estimated marginal means: 32.9 to 33.1, P = .45). BMI was significantly higher for subjects aged < 65 years at Time 1 (F[1, 183] = 4.32, P = .04, partial η² = .02) and at Time 2 (F[1, 183] = 11.04, P = .001, partial η² = .06).

Discussion

This study demonstrated a significant decrease in both weight and BMI at 2 years after the initiation of a PMD in patients aged < 65 years. No significant change was found for obesity rates. However, veterans who met criteria for obesity at the time of PMD prescription saw a significant decrease in their weight at 2 years compared with those who were nonobese.

VHA supports power mobility when there is a clear functional need that cannot be met by rehabilitation, surgical, or medical interventions to enhance veterans’ abilities to access medical care, accomplish necessary tasks of daily living, and to have greater access to their communities. Though limited by strength of association, studies involving PMD users generally found improvement in reported functional outcomes and overall satisfaction with PMD use based on a systematic review.¹³ Nonetheless, there is an implicit concern among providers that a PMD prescription, by limiting physical activity, may exacerbate obesity trends in potentially high-risk individuals.

However, a controversy exists about whether increasing physical activity alone leads to weight loss. A 2007 study followed 102 sedentary men and 100 women over 1 year randomized to moderately intensive exercise for 60 minutes, 6 days a week vs no intervention.¹⁴ The men lost an average of 4 pounds, and women lost an average of 3 pounds after 1 year. The Women’s Health Study divided 39,876 women into high, medium, and low levels of exercise groups. After 10 years, the intense exercise group did not have any significant weight loss.¹⁵

Our study was consistent with existing literature in that a PMD prescription did not correlate with weight gain.^2,9 In our veteran population aged ≥ 65 years, we observed an opposite trend of weight loss after PMD prescription. Of note, studies have shown that peak body weight occurs in the sixth decade, remains stable until about aged 70 years, and then slowly decreases thereafter, at a rate of 0.1 to 0.2 kg per year.¹⁶ This likely explains some of the weight loss trend we observed in our study of veterans aged ≥ 65 years. Possible additional explanations include improved access to health care and to more nutritional foods that promote general health and well-being.

Limitations

The data were gathered from a predominantly male veteran population, potentially limiting generalizability. The health of any individual is determined by the interaction of factors of which body weight is just a single, isolated component. As such, the effect of powered mobility on body weight is not a direct reflection on the effect on overall health. Additionally, there are many factors that may affect an individual’s body weight, such as optimal management of medical comorbidities, which could not be controlled for in this study. Also, while these values can be compared with other veteran populations, this study had no true control group.

Conclusions

Based on the findings of this study with aforementioned limitations, PMD use does not seem to be associated with significant weight changes. Further studies using control groups and assessing comorbidities are needed.

The Veterans Health Administration (VHA) clinical practice recommendations endorse a power mobility device (PMD) for individuals with adequate judgment, cognitive ability, and vision who are unable to propel a manual wheelchair or walk community distances despite standard medical and rehabilitative interventions.¹ VHA supports the use of a PMD in order to access medical care and accomplish activities of daily living, both at home and in the community for veterans with mobility limitations secondary to cardiovascular disease, neurologic disorders, pulmonary disease, or musculoskeletal disorders. The goal of a PMD use is increased participation in community and social life, improved health maintenance via enhanced access to medical facilities, and an overall enhanced quality of life. However, there is a common concern among health care providers that prescribing a PMD may decrease physical activity, in turn, leading to obesity and increasing morbidity. ²

The prevalence of obesity is increasing in the United States. In the past decade 35.0% of men and 36.8% of women were classified as obese (body mass index [BMI], ≥ 30).³ Recent figures from the Centers for Disease Control and Prevention estimate that the overall prevalence of obesity in Americans is closer to 42.4%.⁴ The veteran population is not immune to this; a 2014 study of nearly 5 million veterans reported that the prevalence of obesity in this population was 41%.^5,6 In addition to obesity being implicated in exacerbating many medical problems, such as osteoarthritis, insulin resistance, and heart disease, obesity also is associated with a significant decrease in lifespan.⁷ Almost half of adults who report ambulatory dysfunction are obese.⁸ Given the increased morbidity and mortality as a result of obesity, interventions that may promote weight gain need to be appropriately identified and minimized.

Methods

The institutional review board at Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia, reviewed and approved this study. A waiver of participant consent was approved due to the nature of the research (medical records of patients, some of whom were deceased) and the type of data collected (retrospective data). In addition, each individual was assigned a sequential code to de-identify any personal information. Prosthetics department medical records of consecutive veterans who received PMDs for the first time between January 1, 2011 and June 30, 2012, were reviewed.

Data extracted from the electronic health record (EHR) included demographics, indication for power mobility, weight at time of PMD prescription, weight at 2-years postprescription, and height. Weight readings were considered valid if weight was taken within 3 months of initial prescription and then again within 3 months at the 2-year interval. Individuals without weights recorded in these time frames were excluded. In addition, we excluded medical conditions that might significantly affect body weight, including amyotrophic lateral sclerosis (ALS), amputation during the study period, or history of weight loss surgery. Cancer diagnoses were excluded as they were not an indication for power mobility in the VHA. ALS, though variable in its disease course, was specifically excluded given the likelihood of these patients dying of the natural progression of the disease before the 2-year follow-up period: Median survival times in patients diagnosed with ALS aged > 60 years was < 15 months. ^10-12

The EHRs of 399 individuals who received a PMD during the period were reviewed, and 185 veterans met criteria for data analysis. Subject exclusions in the weight and BMI analysis included death during the follow-up period (89), missing data (68), prior PMD users who came in for replacements (53), and ALS (4) (Figure 1). Patients were not excluded based on the presence or absence of intentional weight loss efforts as this information was not readily available through chart review.

Statistical Analysis

The primary outcome measure was the change in BMI and body weight from time 1 (date of PMD prescription) to time 2 (2 years later). Analyses were performed using IBM SPSS Statistics, Version 21. BMI was calculated using the weight (lb) x 703/ (height [inches]).² Dichotomization of BMI was performed using the conventional cut scores: < 30.0, not obese; and ≥ 30.0, obese. Paired t tests and SPSS general linear model (repeated measures) were used to examine change of BMI from time 1 to time 2. The exact McNemar test was used to examine change in obesity classification across time 1 and time 2. Correlating with Yang’s retrospective observational study, data were analyzed separately for aged < 65 years and aged≥ 65 years.²

Results

Of the 185 veterans, 181 were male (98%); mean age was 67.3 years (range, 26-90); and 55% were aged ≥ 65 years. Musculoskeletal disorders (41.6%) were the most common primary indication for a PMD, followed by pulmonary disorders (25.4%) and cardiovascular disorders (23.8%) (Table 1).

There was a significant decrease in BMI in the first 2 years after receiving a PMD prescription for the first time (estimated marginal means: 31.5 to 30.9 , P = .02). However, age moderated the relationship between BMI and time F[1, 183] = 12.14, P = .001, partial η² = .06 (Table 2). The 101 subjects aged > 65 years experienced a significant decrease in BMI (estimated marginal means: 30.3 to 29.1, P < .001), whereas the 84 patients aged < 65 years experienced a slight and nonsignificant increase in BMI (estimated marginal means: 32.9 to 33.1, P = .45). BMI was significantly higher for subjects aged < 65 years at Time 1 (F[1, 183] = 4.32, P = .04, partial η² = .02) and at Time 2 (F[1, 183] = 11.04, P = .001, partial η² = .06).

Discussion

This study demonstrated a significant decrease in both weight and BMI at 2 years after the initiation of a PMD in patients aged < 65 years. No significant change was found for obesity rates. However, veterans who met criteria for obesity at the time of PMD prescription saw a significant decrease in their weight at 2 years compared with those who were nonobese.

VHA supports power mobility when there is a clear functional need that cannot be met by rehabilitation, surgical, or medical interventions to enhance veterans’ abilities to access medical care, accomplish necessary tasks of daily living, and to have greater access to their communities. Though limited by strength of association, studies involving PMD users generally found improvement in reported functional outcomes and overall satisfaction with PMD use based on a systematic review.¹³ Nonetheless, there is an implicit concern among providers that a PMD prescription, by limiting physical activity, may exacerbate obesity trends in potentially high-risk individuals.

However, a controversy exists about whether increasing physical activity alone leads to weight loss. A 2007 study followed 102 sedentary men and 100 women over 1 year randomized to moderately intensive exercise for 60 minutes, 6 days a week vs no intervention.¹⁴ The men lost an average of 4 pounds, and women lost an average of 3 pounds after 1 year. The Women’s Health Study divided 39,876 women into high, medium, and low levels of exercise groups. After 10 years, the intense exercise group did not have any significant weight loss.¹⁵

Our study was consistent with existing literature in that a PMD prescription did not correlate with weight gain.^2,9 In our veteran population aged ≥ 65 years, we observed an opposite trend of weight loss after PMD prescription. Of note, studies have shown that peak body weight occurs in the sixth decade, remains stable until about aged 70 years, and then slowly decreases thereafter, at a rate of 0.1 to 0.2 kg per year.¹⁶ This likely explains some of the weight loss trend we observed in our study of veterans aged ≥ 65 years. Possible additional explanations include improved access to health care and to more nutritional foods that promote general health and well-being.

Limitations

The data were gathered from a predominantly male veteran population, potentially limiting generalizability. The health of any individual is determined by the interaction of factors of which body weight is just a single, isolated component. As such, the effect of powered mobility on body weight is not a direct reflection on the effect on overall health. Additionally, there are many factors that may affect an individual’s body weight, such as optimal management of medical comorbidities, which could not be controlled for in this study. Also, while these values can be compared with other veteran populations, this study had no true control group.

Conclusions

Based on the findings of this study with aforementioned limitations, PMD use does not seem to be associated with significant weight changes. Further studies using control groups and assessing comorbidities are needed.

The Veterans Health Administration (VHA) clinical practice recommendations endorse a power mobility device (PMD) for individuals with adequate judgment, cognitive ability, and vision who are unable to propel a manual wheelchair or walk community distances despite standard medical and rehabilitative interventions.¹ VHA supports the use of a PMD in order to access medical care and accomplish activities of daily living, both at home and in the community for veterans with mobility limitations secondary to cardiovascular disease, neurologic disorders, pulmonary disease, or musculoskeletal disorders. The goal of a PMD use is increased participation in community and social life, improved health maintenance via enhanced access to medical facilities, and an overall enhanced quality of life. However, there is a common concern among health care providers that prescribing a PMD may decrease physical activity, in turn, leading to obesity and increasing morbidity. ²

The prevalence of obesity is increasing in the United States. In the past decade 35.0% of men and 36.8% of women were classified as obese (body mass index [BMI], ≥ 30).³ Recent figures from the Centers for Disease Control and Prevention estimate that the overall prevalence of obesity in Americans is closer to 42.4%.⁴ The veteran population is not immune to this; a 2014 study of nearly 5 million veterans reported that the prevalence of obesity in this population was 41%.^5,6 In addition to obesity being implicated in exacerbating many medical problems, such as osteoarthritis, insulin resistance, and heart disease, obesity also is associated with a significant decrease in lifespan.⁷ Almost half of adults who report ambulatory dysfunction are obese.⁸ Given the increased morbidity and mortality as a result of obesity, interventions that may promote weight gain need to be appropriately identified and minimized.

Methods

The institutional review board at Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia, reviewed and approved this study. A waiver of participant consent was approved due to the nature of the research (medical records of patients, some of whom were deceased) and the type of data collected (retrospective data). In addition, each individual was assigned a sequential code to de-identify any personal information. Prosthetics department medical records of consecutive veterans who received PMDs for the first time between January 1, 2011 and June 30, 2012, were reviewed.

Data extracted from the electronic health record (EHR) included demographics, indication for power mobility, weight at time of PMD prescription, weight at 2-years postprescription, and height. Weight readings were considered valid if weight was taken within 3 months of initial prescription and then again within 3 months at the 2-year interval. Individuals without weights recorded in these time frames were excluded. In addition, we excluded medical conditions that might significantly affect body weight, including amyotrophic lateral sclerosis (ALS), amputation during the study period, or history of weight loss surgery. Cancer diagnoses were excluded as they were not an indication for power mobility in the VHA. ALS, though variable in its disease course, was specifically excluded given the likelihood of these patients dying of the natural progression of the disease before the 2-year follow-up period: Median survival times in patients diagnosed with ALS aged > 60 years was < 15 months. ^10-12

The EHRs of 399 individuals who received a PMD during the period were reviewed, and 185 veterans met criteria for data analysis. Subject exclusions in the weight and BMI analysis included death during the follow-up period (89), missing data (68), prior PMD users who came in for replacements (53), and ALS (4) (Figure 1). Patients were not excluded based on the presence or absence of intentional weight loss efforts as this information was not readily available through chart review.

Statistical Analysis

The primary outcome measure was the change in BMI and body weight from time 1 (date of PMD prescription) to time 2 (2 years later). Analyses were performed using IBM SPSS Statistics, Version 21. BMI was calculated using the weight (lb) x 703/ (height [inches]).² Dichotomization of BMI was performed using the conventional cut scores: < 30.0, not obese; and ≥ 30.0, obese. Paired t tests and SPSS general linear model (repeated measures) were used to examine change of BMI from time 1 to time 2. The exact McNemar test was used to examine change in obesity classification across time 1 and time 2. Correlating with Yang’s retrospective observational study, data were analyzed separately for aged < 65 years and aged≥ 65 years.²

Results

Of the 185 veterans, 181 were male (98%); mean age was 67.3 years (range, 26-90); and 55% were aged ≥ 65 years. Musculoskeletal disorders (41.6%) were the most common primary indication for a PMD, followed by pulmonary disorders (25.4%) and cardiovascular disorders (23.8%) (Table 1).

There was a significant decrease in BMI in the first 2 years after receiving a PMD prescription for the first time (estimated marginal means: 31.5 to 30.9 , P = .02). However, age moderated the relationship between BMI and time F[1, 183] = 12.14, P = .001, partial η² = .06 (Table 2). The 101 subjects aged > 65 years experienced a significant decrease in BMI (estimated marginal means: 30.3 to 29.1, P < .001), whereas the 84 patients aged < 65 years experienced a slight and nonsignificant increase in BMI (estimated marginal means: 32.9 to 33.1, P = .45). BMI was significantly higher for subjects aged < 65 years at Time 1 (F[1, 183] = 4.32, P = .04, partial η² = .02) and at Time 2 (F[1, 183] = 11.04, P = .001, partial η² = .06).

Discussion

This study demonstrated a significant decrease in both weight and BMI at 2 years after the initiation of a PMD in patients aged < 65 years. No significant change was found for obesity rates. However, veterans who met criteria for obesity at the time of PMD prescription saw a significant decrease in their weight at 2 years compared with those who were nonobese.

VHA supports power mobility when there is a clear functional need that cannot be met by rehabilitation, surgical, or medical interventions to enhance veterans’ abilities to access medical care, accomplish necessary tasks of daily living, and to have greater access to their communities. Though limited by strength of association, studies involving PMD users generally found improvement in reported functional outcomes and overall satisfaction with PMD use based on a systematic review.¹³ Nonetheless, there is an implicit concern among providers that a PMD prescription, by limiting physical activity, may exacerbate obesity trends in potentially high-risk individuals.

However, a controversy exists about whether increasing physical activity alone leads to weight loss. A 2007 study followed 102 sedentary men and 100 women over 1 year randomized to moderately intensive exercise for 60 minutes, 6 days a week vs no intervention.¹⁴ The men lost an average of 4 pounds, and women lost an average of 3 pounds after 1 year. The Women’s Health Study divided 39,876 women into high, medium, and low levels of exercise groups. After 10 years, the intense exercise group did not have any significant weight loss.¹⁵

Our study was consistent with existing literature in that a PMD prescription did not correlate with weight gain.^2,9 In our veteran population aged ≥ 65 years, we observed an opposite trend of weight loss after PMD prescription. Of note, studies have shown that peak body weight occurs in the sixth decade, remains stable until about aged 70 years, and then slowly decreases thereafter, at a rate of 0.1 to 0.2 kg per year.¹⁶ This likely explains some of the weight loss trend we observed in our study of veterans aged ≥ 65 years. Possible additional explanations include improved access to health care and to more nutritional foods that promote general health and well-being.

Limitations

The data were gathered from a predominantly male veteran population, potentially limiting generalizability. The health of any individual is determined by the interaction of factors of which body weight is just a single, isolated component. As such, the effect of powered mobility on body weight is not a direct reflection on the effect on overall health. Additionally, there are many factors that may affect an individual’s body weight, such as optimal management of medical comorbidities, which could not be controlled for in this study. Also, while these values can be compared with other veteran populations, this study had no true control group.

Conclusions

Based on the findings of this study with aforementioned limitations, PMD use does not seem to be associated with significant weight changes. Further studies using control groups and assessing comorbidities are needed.

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

Allergies to β-lactam antibiotics are among the most documented drug allergies, and approximately 10% of the US population reports an allergy specifically to penicillin.^1,2 Many allergic reactions are mediated via the antibody immunoglobulin E (IgE), producing an immediate hypersensitivity response, such as hives or anaphylaxis, which can be life threatening. Reactions also may be mediated by T cells of the immune system, which target various cell lines and can cause a drug reaction with eosinophilia and systemic symptoms or Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).³Although β-lactam and penicillin allergies are frequently reported, < 5% manifest as either an IgE or T-cell–mediated response.⁴Furthermore, for the small proportion of patients who once had a true IgE-mediated reaction, including anaphylaxis, 80% experience a decrease in IgE antibodies over time, resulting in a loss of allergic response after about 10 years.² Due to this decline in IgE response and the initial mislabeling of mild non-IgE penicillin reactions, 95% of patients who are labeled as penicillin-allergic can eventually tolerate a penicillin.²

When a patient’s β-lactam allergy is never reevaluated, negative consequences can ensue. This allergy in a patient’s medical record can lead to the inappropriate avoidance of the entire β-lactam antibiotic class, which includes all penicillins, cephalosporins, and carbapenems. Withholding these antibiotics in certain situations can lead to negative patient outcomes.^5-7 For example, the drugs of choice for the infections syphilis and methicillin-susceptible Staphylococcus aureus (S aureus) are a penicillin or cephalosporin, and patients labeled as penicillin-allergic are more likely to experience treatment failure from using second-line therapies.⁸ Additionally, receiving non-β-lactam antibiotics puts patients at risk of multidrug-resistant pathogens like methicillin-resistant S aureus and vancomycin-resistant Enterococcus (VRE) as well as adverse effects, such as Clostridioides difficile infection.⁹ Using alternative, and likely broad-spectrum, antibiotics also can be financially detrimental: These medications often are more costly than their β-lactam alternatives, and the inappropriate use of therapies can result in longer hospital courses.^9-11

Penicillin allergies can complicate the antibiotic treatment strategy. The Memphis Veterans Affairs Medical Center (MVAMC) in Tennessee recently examined the negative sequelae of β-lactam allergies and found that more than half the patients received inappropriate antibiotics based on guideline recommendations, allergy history, and culture and sensitivity data.¹² To mitigate the problems for patients with β-lactam allergies, the 2016 guidelines from the Infectious Diseases Society of America (IDSA) on the Implementation of Antimicrobial Stewardship Programs (ASP) recommend that these patients undergo allergy assessment and penicillin skin testing.¹³In November 2017, MVAMC implemented such a process. The purpose of this study was to describe our pharmacist-run β-lactam allergy assessment (BLAA) protocol and penicillin allergy clinic (PAC) and evaluate their overall outcomes: the proportion of patients who have been cleared to receive an alternative β-lactam antibiotic or who have had their allergy removed altogether.

Methods

We conducted a retrospective, observational study with approval from the institutional review board at MVAMC. This institution is an academic teaching center with 240 acute care beds and a variety of outpatient clinics available at the main campus, serving veterans in Memphis and the Mid-South area, including west Tennessee, northern Mississippi, and northeastern Arkansas. Patients were consecutively evaluated from November 2017 through February 2020. All MVAMC patients with a documented β-lactam allergy were eligible for inclusion; there were no exclusion criteria. Electronic health record data were assessed and included basic patient demographics, allergy history, and the outcome of the BLAA and PAC. Descriptive statistics were used for data analysis.

The purpose of the BLAA process is to evaluate, clarify, and potentially clear patients of their β-lactam allergies. Started in November 2017, the process includes appropriate patient screening with documentation of the β-lactam allergy. When patients with a β-lactam allergy are admitted to the hospital, they are interviewed by an inpatient CPS. This pharmacist then enters an assessment into the patient’s chart, which includes details of the allergen, reaction, and timing of the event. Based on this information, the CPS provides recommendations: clearance for alternative β-lactams, avoidance of all β-lactams, or removal of the allergy.

In January 2019, the pharmacist-driven penicillin allergy clinic (PAC) was started. Eligible patients receive a skin test to confirm or rule out their allergy after hospital discharge. To facilitate patient identification and screening, the ASP/infectious diseases (ID) clinical pharmacist runs a daily report of hospitalized patients with documented β-lactam allergies. All inpatient CPSs had access to this report and could easily identify and interview patients. Following the interview, the pharmacist enters a note in the patient’s chart, using the BLAA template (eFigures 1 and 2). On completion, a note is viewable in the Notes section adjacent to the patient’s allergies. The pharmacist then can enter a PAC consult for eligible patients. Although most patients qualify for PAC, exclusion criteria include non–IgE-mediated allergies (ie, SJS/TEN), allergies to β-lactams other than penicillins, or recent reactions (ie, within the past 5 years). Each inpatient CPS is trained on this BLAA process, which includes patient screening, chart review, patient interviewing, and the BLAA template and note completion. Pharmacists must demonstrate competency in completing 5 BLAA notes with review from the ASP/ID pharmacist. Once training is completed, this process is integrated into the pharmacist’s everyday workflow.

Results

We evaluated 278 patients, using the BLAA protocol. In this veteran population, patients were generally older males and evenly split between African American and White patients (Table 2). Most patients reported an allergy to penicillin, with a rash being the most common reaction (Table 3).

Of the 278 assessed, 246 patients were evaluated via our BLAA alone and were not seen in PAC. We were able to remove 25% of these patients’ allergies by performing a thorough assessment. Of the 184 patients whose allergies could not be removed via the BLAA alone, 147 (80%) were still eligible for PAC but are awaiting scheduling. Patients ineligible for PAC included those with a cephalosporin allergy or a severe and non–IgE-mediated reaction. Other ineligible patients who were not eligible included those with diseases where risk of testing outweighed the benefits.

Of the 32 patients who were seen in PAC, 75% of allergies were removed through direct testing. No differences between race or gender were observed. Of the 8 patients (25%) whose allergies were not removed, 5 had confirmed penicillin allergies with a positive reaction; 4 of these patients have since tolerated an alternative β-lactam (either a cephalosporin or carbapenem). Three patients had inconclusive tests, most often because their positive control was nonreactive during the percutaneous portion of the skin test; these allergies could neither be confirmed nor removed. Two of these patients have since tolerated alternative β-lactams (both cephalosporins). Although these 8 patients should not be rechallenged with a penicillin antibiotic, they could still be considered for alternative β-lactams, based on the nature and histories of their allergies.

Discussion

We have implemented a unique and efficient way to evaluate, clarify, and clear β-lactam allergies. Our BLAA protocol allows for a smooth process by distributing the workload of evaluating and clarifying patients’ allergies over many inpatient CPS. Furthermore, the BLAA is readily accessible to health care providers (HCPs), allowing for optimal clinical decision making. HCPs can quickly gather further information on the β-lactam allergy, while seeing actionable recommendations, along with documentation of the PAC visit and subsequent events, if the patient has been seen.

This study demonstrated the promotion of alternative β-lactam use for nearly all patients: 99% of our patient population were deemed candidates for a β-lactam type antibiotic. This percentage included patients whose allergies have been fully cleared, both through BLAA alone and in PAC. Also included are patients who have been cleared for an alternative β-lactam and not necessarily a penicillin.

In our PAC, 8 patients were not cleared for penicillins: 5 had penicillin allergies confirmed, and 3 had inconclusive results. Based on the nature of their reactions and previous tolerance of alternative β-lactams, those 5 patients are still eligible for alternative β-lactams. Additionally, the 3 patients with inconclusive results are also eligible for alternative β-lactams for the same reasons. The patients for whom β-lactam antibiotic avoidance was recommended (4 patients, 1%) have not been seen in PAC, as their reactions disqualify them from penicillin skin testing. Two of these patients had anaphylaxis < 5 years ago and will be eligible for PAC if they do not experience anaphylaxis within the 5-year period.

Limitations

Although our study demonstrates many benefits of implementation of a BLAA protocol and PAC, it has several limitations. This analysis was a retrospective review of the limited number of patients who had assessments completed. Additionally, many patients were waiting to be seen in PAC. This delay is largely due to the length of time to establish our pharmacist-run PAC, the limited number of pharmacists trained and available for skin testing, the time constraints of our staff, and COVID-19 pandemic. Additionally, only pharmacists administer the BLAA questionnaire, but this process could be expanded to other professionals such as nursing staff. Also, this study was not set up as a before-and-after analysis that examined outcomes associated with individual patients. Future directions include assessing the clinical impact of this protocol, such as evaluating provider utilization of β-lactam antibiotics for patients with penicillin allergies and determining associated cost savings.

Conclusions

This study demonstrated that implementation of a pharmacist-driven BLAA protocol and PAC can effectively remove inaccurate penicillin allergy labels and clear patients for alternative β-lactam antibiotic use. The BLAA process in conjunction with PAC will continue to be used to better evaluate, clarify, and clear patient allergies to optimize their care.

Allergies to β-lactam antibiotics are among the most documented drug allergies, and approximately 10% of the US population reports an allergy specifically to penicillin.^1,2 Many allergic reactions are mediated via the antibody immunoglobulin E (IgE), producing an immediate hypersensitivity response, such as hives or anaphylaxis, which can be life threatening. Reactions also may be mediated by T cells of the immune system, which target various cell lines and can cause a drug reaction with eosinophilia and systemic symptoms or Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).³Although β-lactam and penicillin allergies are frequently reported, < 5% manifest as either an IgE or T-cell–mediated response.⁴Furthermore, for the small proportion of patients who once had a true IgE-mediated reaction, including anaphylaxis, 80% experience a decrease in IgE antibodies over time, resulting in a loss of allergic response after about 10 years.² Due to this decline in IgE response and the initial mislabeling of mild non-IgE penicillin reactions, 95% of patients who are labeled as penicillin-allergic can eventually tolerate a penicillin.²

When a patient’s β-lactam allergy is never reevaluated, negative consequences can ensue. This allergy in a patient’s medical record can lead to the inappropriate avoidance of the entire β-lactam antibiotic class, which includes all penicillins, cephalosporins, and carbapenems. Withholding these antibiotics in certain situations can lead to negative patient outcomes.^5-7 For example, the drugs of choice for the infections syphilis and methicillin-susceptible Staphylococcus aureus (S aureus) are a penicillin or cephalosporin, and patients labeled as penicillin-allergic are more likely to experience treatment failure from using second-line therapies.⁸ Additionally, receiving non-β-lactam antibiotics puts patients at risk of multidrug-resistant pathogens like methicillin-resistant S aureus and vancomycin-resistant Enterococcus (VRE) as well as adverse effects, such as Clostridioides difficile infection.⁹ Using alternative, and likely broad-spectrum, antibiotics also can be financially detrimental: These medications often are more costly than their β-lactam alternatives, and the inappropriate use of therapies can result in longer hospital courses.^9-11

Penicillin allergies can complicate the antibiotic treatment strategy. The Memphis Veterans Affairs Medical Center (MVAMC) in Tennessee recently examined the negative sequelae of β-lactam allergies and found that more than half the patients received inappropriate antibiotics based on guideline recommendations, allergy history, and culture and sensitivity data.¹² To mitigate the problems for patients with β-lactam allergies, the 2016 guidelines from the Infectious Diseases Society of America (IDSA) on the Implementation of Antimicrobial Stewardship Programs (ASP) recommend that these patients undergo allergy assessment and penicillin skin testing.¹³In November 2017, MVAMC implemented such a process. The purpose of this study was to describe our pharmacist-run β-lactam allergy assessment (BLAA) protocol and penicillin allergy clinic (PAC) and evaluate their overall outcomes: the proportion of patients who have been cleared to receive an alternative β-lactam antibiotic or who have had their allergy removed altogether.

Methods

We conducted a retrospective, observational study with approval from the institutional review board at MVAMC. This institution is an academic teaching center with 240 acute care beds and a variety of outpatient clinics available at the main campus, serving veterans in Memphis and the Mid-South area, including west Tennessee, northern Mississippi, and northeastern Arkansas. Patients were consecutively evaluated from November 2017 through February 2020. All MVAMC patients with a documented β-lactam allergy were eligible for inclusion; there were no exclusion criteria. Electronic health record data were assessed and included basic patient demographics, allergy history, and the outcome of the BLAA and PAC. Descriptive statistics were used for data analysis.

The purpose of the BLAA process is to evaluate, clarify, and potentially clear patients of their β-lactam allergies. Started in November 2017, the process includes appropriate patient screening with documentation of the β-lactam allergy. When patients with a β-lactam allergy are admitted to the hospital, they are interviewed by an inpatient CPS. This pharmacist then enters an assessment into the patient’s chart, which includes details of the allergen, reaction, and timing of the event. Based on this information, the CPS provides recommendations: clearance for alternative β-lactams, avoidance of all β-lactams, or removal of the allergy.

In January 2019, the pharmacist-driven penicillin allergy clinic (PAC) was started. Eligible patients receive a skin test to confirm or rule out their allergy after hospital discharge. To facilitate patient identification and screening, the ASP/infectious diseases (ID) clinical pharmacist runs a daily report of hospitalized patients with documented β-lactam allergies. All inpatient CPSs had access to this report and could easily identify and interview patients. Following the interview, the pharmacist enters a note in the patient’s chart, using the BLAA template (eFigures 1 and 2). On completion, a note is viewable in the Notes section adjacent to the patient’s allergies. The pharmacist then can enter a PAC consult for eligible patients. Although most patients qualify for PAC, exclusion criteria include non–IgE-mediated allergies (ie, SJS/TEN), allergies to β-lactams other than penicillins, or recent reactions (ie, within the past 5 years). Each inpatient CPS is trained on this BLAA process, which includes patient screening, chart review, patient interviewing, and the BLAA template and note completion. Pharmacists must demonstrate competency in completing 5 BLAA notes with review from the ASP/ID pharmacist. Once training is completed, this process is integrated into the pharmacist’s everyday workflow.

Results

We evaluated 278 patients, using the BLAA protocol. In this veteran population, patients were generally older males and evenly split between African American and White patients (Table 2). Most patients reported an allergy to penicillin, with a rash being the most common reaction (Table 3).

Of the 278 assessed, 246 patients were evaluated via our BLAA alone and were not seen in PAC. We were able to remove 25% of these patients’ allergies by performing a thorough assessment. Of the 184 patients whose allergies could not be removed via the BLAA alone, 147 (80%) were still eligible for PAC but are awaiting scheduling. Patients ineligible for PAC included those with a cephalosporin allergy or a severe and non–IgE-mediated reaction. Other ineligible patients who were not eligible included those with diseases where risk of testing outweighed the benefits.

Of the 32 patients who were seen in PAC, 75% of allergies were removed through direct testing. No differences between race or gender were observed. Of the 8 patients (25%) whose allergies were not removed, 5 had confirmed penicillin allergies with a positive reaction; 4 of these patients have since tolerated an alternative β-lactam (either a cephalosporin or carbapenem). Three patients had inconclusive tests, most often because their positive control was nonreactive during the percutaneous portion of the skin test; these allergies could neither be confirmed nor removed. Two of these patients have since tolerated alternative β-lactams (both cephalosporins). Although these 8 patients should not be rechallenged with a penicillin antibiotic, they could still be considered for alternative β-lactams, based on the nature and histories of their allergies.

Discussion

We have implemented a unique and efficient way to evaluate, clarify, and clear β-lactam allergies. Our BLAA protocol allows for a smooth process by distributing the workload of evaluating and clarifying patients’ allergies over many inpatient CPS. Furthermore, the BLAA is readily accessible to health care providers (HCPs), allowing for optimal clinical decision making. HCPs can quickly gather further information on the β-lactam allergy, while seeing actionable recommendations, along with documentation of the PAC visit and subsequent events, if the patient has been seen.

This study demonstrated the promotion of alternative β-lactam use for nearly all patients: 99% of our patient population were deemed candidates for a β-lactam type antibiotic. This percentage included patients whose allergies have been fully cleared, both through BLAA alone and in PAC. Also included are patients who have been cleared for an alternative β-lactam and not necessarily a penicillin.

In our PAC, 8 patients were not cleared for penicillins: 5 had penicillin allergies confirmed, and 3 had inconclusive results. Based on the nature of their reactions and previous tolerance of alternative β-lactams, those 5 patients are still eligible for alternative β-lactams. Additionally, the 3 patients with inconclusive results are also eligible for alternative β-lactams for the same reasons. The patients for whom β-lactam antibiotic avoidance was recommended (4 patients, 1%) have not been seen in PAC, as their reactions disqualify them from penicillin skin testing. Two of these patients had anaphylaxis < 5 years ago and will be eligible for PAC if they do not experience anaphylaxis within the 5-year period.

Limitations

Although our study demonstrates many benefits of implementation of a BLAA protocol and PAC, it has several limitations. This analysis was a retrospective review of the limited number of patients who had assessments completed. Additionally, many patients were waiting to be seen in PAC. This delay is largely due to the length of time to establish our pharmacist-run PAC, the limited number of pharmacists trained and available for skin testing, the time constraints of our staff, and COVID-19 pandemic. Additionally, only pharmacists administer the BLAA questionnaire, but this process could be expanded to other professionals such as nursing staff. Also, this study was not set up as a before-and-after analysis that examined outcomes associated with individual patients. Future directions include assessing the clinical impact of this protocol, such as evaluating provider utilization of β-lactam antibiotics for patients with penicillin allergies and determining associated cost savings.

Conclusions

This study demonstrated that implementation of a pharmacist-driven BLAA protocol and PAC can effectively remove inaccurate penicillin allergy labels and clear patients for alternative β-lactam antibiotic use. The BLAA process in conjunction with PAC will continue to be used to better evaluate, clarify, and clear patient allergies to optimize their care.

Allergies to β-lactam antibiotics are among the most documented drug allergies, and approximately 10% of the US population reports an allergy specifically to penicillin.^1,2 Many allergic reactions are mediated via the antibody immunoglobulin E (IgE), producing an immediate hypersensitivity response, such as hives or anaphylaxis, which can be life threatening. Reactions also may be mediated by T cells of the immune system, which target various cell lines and can cause a drug reaction with eosinophilia and systemic symptoms or Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).³Although β-lactam and penicillin allergies are frequently reported, < 5% manifest as either an IgE or T-cell–mediated response.⁴Furthermore, for the small proportion of patients who once had a true IgE-mediated reaction, including anaphylaxis, 80% experience a decrease in IgE antibodies over time, resulting in a loss of allergic response after about 10 years.² Due to this decline in IgE response and the initial mislabeling of mild non-IgE penicillin reactions, 95% of patients who are labeled as penicillin-allergic can eventually tolerate a penicillin.²

When a patient’s β-lactam allergy is never reevaluated, negative consequences can ensue. This allergy in a patient’s medical record can lead to the inappropriate avoidance of the entire β-lactam antibiotic class, which includes all penicillins, cephalosporins, and carbapenems. Withholding these antibiotics in certain situations can lead to negative patient outcomes.^5-7 For example, the drugs of choice for the infections syphilis and methicillin-susceptible Staphylococcus aureus (S aureus) are a penicillin or cephalosporin, and patients labeled as penicillin-allergic are more likely to experience treatment failure from using second-line therapies.⁸ Additionally, receiving non-β-lactam antibiotics puts patients at risk of multidrug-resistant pathogens like methicillin-resistant S aureus and vancomycin-resistant Enterococcus (VRE) as well as adverse effects, such as Clostridioides difficile infection.⁹ Using alternative, and likely broad-spectrum, antibiotics also can be financially detrimental: These medications often are more costly than their β-lactam alternatives, and the inappropriate use of therapies can result in longer hospital courses.^9-11

Penicillin allergies can complicate the antibiotic treatment strategy. The Memphis Veterans Affairs Medical Center (MVAMC) in Tennessee recently examined the negative sequelae of β-lactam allergies and found that more than half the patients received inappropriate antibiotics based on guideline recommendations, allergy history, and culture and sensitivity data.¹² To mitigate the problems for patients with β-lactam allergies, the 2016 guidelines from the Infectious Diseases Society of America (IDSA) on the Implementation of Antimicrobial Stewardship Programs (ASP) recommend that these patients undergo allergy assessment and penicillin skin testing.¹³In November 2017, MVAMC implemented such a process. The purpose of this study was to describe our pharmacist-run β-lactam allergy assessment (BLAA) protocol and penicillin allergy clinic (PAC) and evaluate their overall outcomes: the proportion of patients who have been cleared to receive an alternative β-lactam antibiotic or who have had their allergy removed altogether.

Methods

We conducted a retrospective, observational study with approval from the institutional review board at MVAMC. This institution is an academic teaching center with 240 acute care beds and a variety of outpatient clinics available at the main campus, serving veterans in Memphis and the Mid-South area, including west Tennessee, northern Mississippi, and northeastern Arkansas. Patients were consecutively evaluated from November 2017 through February 2020. All MVAMC patients with a documented β-lactam allergy were eligible for inclusion; there were no exclusion criteria. Electronic health record data were assessed and included basic patient demographics, allergy history, and the outcome of the BLAA and PAC. Descriptive statistics were used for data analysis.

The purpose of the BLAA process is to evaluate, clarify, and potentially clear patients of their β-lactam allergies. Started in November 2017, the process includes appropriate patient screening with documentation of the β-lactam allergy. When patients with a β-lactam allergy are admitted to the hospital, they are interviewed by an inpatient CPS. This pharmacist then enters an assessment into the patient’s chart, which includes details of the allergen, reaction, and timing of the event. Based on this information, the CPS provides recommendations: clearance for alternative β-lactams, avoidance of all β-lactams, or removal of the allergy.

In January 2019, the pharmacist-driven penicillin allergy clinic (PAC) was started. Eligible patients receive a skin test to confirm or rule out their allergy after hospital discharge. To facilitate patient identification and screening, the ASP/infectious diseases (ID) clinical pharmacist runs a daily report of hospitalized patients with documented β-lactam allergies. All inpatient CPSs had access to this report and could easily identify and interview patients. Following the interview, the pharmacist enters a note in the patient’s chart, using the BLAA template (eFigures 1 and 2). On completion, a note is viewable in the Notes section adjacent to the patient’s allergies. The pharmacist then can enter a PAC consult for eligible patients. Although most patients qualify for PAC, exclusion criteria include non–IgE-mediated allergies (ie, SJS/TEN), allergies to β-lactams other than penicillins, or recent reactions (ie, within the past 5 years). Each inpatient CPS is trained on this BLAA process, which includes patient screening, chart review, patient interviewing, and the BLAA template and note completion. Pharmacists must demonstrate competency in completing 5 BLAA notes with review from the ASP/ID pharmacist. Once training is completed, this process is integrated into the pharmacist’s everyday workflow.

Results

We evaluated 278 patients, using the BLAA protocol. In this veteran population, patients were generally older males and evenly split between African American and White patients (Table 2). Most patients reported an allergy to penicillin, with a rash being the most common reaction (Table 3).

Of the 278 assessed, 246 patients were evaluated via our BLAA alone and were not seen in PAC. We were able to remove 25% of these patients’ allergies by performing a thorough assessment. Of the 184 patients whose allergies could not be removed via the BLAA alone, 147 (80%) were still eligible for PAC but are awaiting scheduling. Patients ineligible for PAC included those with a cephalosporin allergy or a severe and non–IgE-mediated reaction. Other ineligible patients who were not eligible included those with diseases where risk of testing outweighed the benefits.

Of the 32 patients who were seen in PAC, 75% of allergies were removed through direct testing. No differences between race or gender were observed. Of the 8 patients (25%) whose allergies were not removed, 5 had confirmed penicillin allergies with a positive reaction; 4 of these patients have since tolerated an alternative β-lactam (either a cephalosporin or carbapenem). Three patients had inconclusive tests, most often because their positive control was nonreactive during the percutaneous portion of the skin test; these allergies could neither be confirmed nor removed. Two of these patients have since tolerated alternative β-lactams (both cephalosporins). Although these 8 patients should not be rechallenged with a penicillin antibiotic, they could still be considered for alternative β-lactams, based on the nature and histories of their allergies.

Discussion

We have implemented a unique and efficient way to evaluate, clarify, and clear β-lactam allergies. Our BLAA protocol allows for a smooth process by distributing the workload of evaluating and clarifying patients’ allergies over many inpatient CPS. Furthermore, the BLAA is readily accessible to health care providers (HCPs), allowing for optimal clinical decision making. HCPs can quickly gather further information on the β-lactam allergy, while seeing actionable recommendations, along with documentation of the PAC visit and subsequent events, if the patient has been seen.

This study demonstrated the promotion of alternative β-lactam use for nearly all patients: 99% of our patient population were deemed candidates for a β-lactam type antibiotic. This percentage included patients whose allergies have been fully cleared, both through BLAA alone and in PAC. Also included are patients who have been cleared for an alternative β-lactam and not necessarily a penicillin.

In our PAC, 8 patients were not cleared for penicillins: 5 had penicillin allergies confirmed, and 3 had inconclusive results. Based on the nature of their reactions and previous tolerance of alternative β-lactams, those 5 patients are still eligible for alternative β-lactams. Additionally, the 3 patients with inconclusive results are also eligible for alternative β-lactams for the same reasons. The patients for whom β-lactam antibiotic avoidance was recommended (4 patients, 1%) have not been seen in PAC, as their reactions disqualify them from penicillin skin testing. Two of these patients had anaphylaxis < 5 years ago and will be eligible for PAC if they do not experience anaphylaxis within the 5-year period.

Limitations

Although our study demonstrates many benefits of implementation of a BLAA protocol and PAC, it has several limitations. This analysis was a retrospective review of the limited number of patients who had assessments completed. Additionally, many patients were waiting to be seen in PAC. This delay is largely due to the length of time to establish our pharmacist-run PAC, the limited number of pharmacists trained and available for skin testing, the time constraints of our staff, and COVID-19 pandemic. Additionally, only pharmacists administer the BLAA questionnaire, but this process could be expanded to other professionals such as nursing staff. Also, this study was not set up as a before-and-after analysis that examined outcomes associated with individual patients. Future directions include assessing the clinical impact of this protocol, such as evaluating provider utilization of β-lactam antibiotics for patients with penicillin allergies and determining associated cost savings.

Conclusions

This study demonstrated that implementation of a pharmacist-driven BLAA protocol and PAC can effectively remove inaccurate penicillin allergy labels and clear patients for alternative β-lactam antibiotic use. The BLAA process in conjunction with PAC will continue to be used to better evaluate, clarify, and clear patient allergies to optimize their care.

Several weeks ago, I received a call from my brother who, though not a health care professional, wanted me to know he thought the public was being too critical of scientists and physicians who “are giving us the best advice they can about COVID. People think they should have all the answers. But this virus is complicated, and they don’t always know what is going to happen next.” What makes his charitable read of the public health situation remarkable is that he is a COVID-19 survivor of one of the first reported cases of Guillain-Barre syndrome, which several expert neurologists believe is the result of COVID-19. Like so many other COVID-19 long-haul patients, he is left with lingering symptoms and residual deficits.¹

I use this personal story as the overture to this piece on why I am changing my opinion regarding a COVID-19 mandate for federal practitioners. In June I raised ethical concerns about compelling vaccination especially for service members of color based on a current and historical climate of mistrust and discrimination in health care that compulsory vaccination could exacerbate.² Instead, I followed the lead of Secretary of Defense J. Lloyd Austin III and advocated continued education and encouragement for vaccine-hesitant troops.³ So in 2 months what has so radically changed to lead Secretary Austin and US Department of Veterans Affairs (VA) Secretary Denis R. McDonough to mandate vaccination for their workforce?^4,5

I am calling the change the Delta Factor. This is not to be confused with the spy-thrillers that ironically involved rescuing a scientist! The Delta Factor is a catch-all phrase to cover the protean public health impacts of the devastating COVID-19 Delta variant now ravaging the country. Depending on the area of the country as of mid-August, the Centers for Disease Control and Prevention (CDC) estimated that 80% to > 90% of new cases were the Delta variant.⁶ An increasing number of these cases sadly are in children.⁷

According to the CDC, the Delta variant is more than twice as contagious as index or subsequent strains: making it about as contagious as chicken pox. The unvaccinated are the most susceptible to Delta and may develop more serious illness and risk of death than with other strains. Those who are fully vaccinated can still contract the virus although usually with milder cases. More worrisome is that individuals with these breakthrough infections have the same viral load as those without vaccinations, rendering them vectors of transmission, although for a shorter time than unvaccinated persons.⁸

The VA first mandated vaccination among its health care employees in July and then expanded it to all staff in August.⁹ The US Department of Defense (DoD) mandatory vaccination was announced prior to US Food and Drug Administration’s (FDA) full approval of the Pfizer-BioNTech vaccine.¹⁰ Secretary Austin asked President Biden to grant a waiver to permit mandatory vaccination even without full FDA approval, and Biden has indicated his support, but the full approval expedited the time line for implementation.¹¹

Both agencies directly referenced Delta as a primary reason for their vaccination mandates. The VA argued that the mandate was necessary to protect the safety of veterans, while the DoD noted that vaccination was essential to ensure the health of the fighting force. In his initial announcement, Secretary McDonough explicitly mentioned the Delta variant as a primary reason for his decision. noting “it’s the best way to keep veterans safe, especially as the Delta variant spreads across the country.”⁴ Similarly, Secretary Austin declared, “We will also be keeping a close eye on infection rates, which are on the rise now due to the Delta variant and the impact these rates might have on our readiness.”⁵

VA and DoD leadership emphasized the safety and effectiveness of the vaccine and urged employees to voluntarily obtain the vaccine or obtain a religious or medical exemption. Those without such an exemption must adhere to masking, testing, and other restrictions.⁵ As anticipated in the earlier editorial, there has been opposition to the mandate from the workforce of the 2 agencies and their political supporters some of whom view vaccine mandates as violations of personal liberty and bodily integrity and for whom rampant disinformation has amplified entrenched distrust of the government.¹²

The decision to shift from voluntary to mandatory vaccination of federal employees responsible for the health care of veterans and the defense of citizens, which may seem draconian to some, is grounded in core public health ethical and legal principles. The first is the doctrine of the least restrictive alternative, which dictates that implemented public health policies should have the least infringement on individual liberties as possible.¹³ A corollary is that less coercive methods should be reasonably attempted before moving to more restrictive policies. Both agencies have struggled somewhat unsuccessfully to vaccinate employees even with extensive education, persuasion, and incentives. In July, the active-duty vaccination rates ranged from 58 to 77%; among VA employees it ranged from 59 to 85%, depending on the facility.¹⁴

Finally and most important, for a vaccine or other public health intervention to be ethically mandated it must have a high probability of attaining a serious purpose: here preventing the harms of sickness and death especially in the most vulnerable. In July, the White House COVID-19 Response Team reported that “preliminary data from several states over the last few months suggest that 99.5% of deaths from COVID-19 in the United States were in unvaccinated people” and were preventable.¹⁵ Ethically, even as mandates are implemented across the federal workforce, efforts to educate, encourage, and empower vaccination especially among disenfranchised cohorts must continue. But as a recently leaked CDC internal document acknowledged about the Delta Factor, “the war has changed” and so has my opinion about mandating vaccination among those upon whose service depends the life and security of us all.¹⁶

Several weeks ago, I received a call from my brother who, though not a health care professional, wanted me to know he thought the public was being too critical of scientists and physicians who “are giving us the best advice they can about COVID. People think they should have all the answers. But this virus is complicated, and they don’t always know what is going to happen next.” What makes his charitable read of the public health situation remarkable is that he is a COVID-19 survivor of one of the first reported cases of Guillain-Barre syndrome, which several expert neurologists believe is the result of COVID-19. Like so many other COVID-19 long-haul patients, he is left with lingering symptoms and residual deficits.¹

I use this personal story as the overture to this piece on why I am changing my opinion regarding a COVID-19 mandate for federal practitioners. In June I raised ethical concerns about compelling vaccination especially for service members of color based on a current and historical climate of mistrust and discrimination in health care that compulsory vaccination could exacerbate.² Instead, I followed the lead of Secretary of Defense J. Lloyd Austin III and advocated continued education and encouragement for vaccine-hesitant troops.³ So in 2 months what has so radically changed to lead Secretary Austin and US Department of Veterans Affairs (VA) Secretary Denis R. McDonough to mandate vaccination for their workforce?^4,5

I am calling the change the Delta Factor. This is not to be confused with the spy-thrillers that ironically involved rescuing a scientist! The Delta Factor is a catch-all phrase to cover the protean public health impacts of the devastating COVID-19 Delta variant now ravaging the country. Depending on the area of the country as of mid-August, the Centers for Disease Control and Prevention (CDC) estimated that 80% to > 90% of new cases were the Delta variant.⁶ An increasing number of these cases sadly are in children.⁷

According to the CDC, the Delta variant is more than twice as contagious as index or subsequent strains: making it about as contagious as chicken pox. The unvaccinated are the most susceptible to Delta and may develop more serious illness and risk of death than with other strains. Those who are fully vaccinated can still contract the virus although usually with milder cases. More worrisome is that individuals with these breakthrough infections have the same viral load as those without vaccinations, rendering them vectors of transmission, although for a shorter time than unvaccinated persons.⁸

The VA first mandated vaccination among its health care employees in July and then expanded it to all staff in August.⁹ The US Department of Defense (DoD) mandatory vaccination was announced prior to US Food and Drug Administration’s (FDA) full approval of the Pfizer-BioNTech vaccine.¹⁰ Secretary Austin asked President Biden to grant a waiver to permit mandatory vaccination even without full FDA approval, and Biden has indicated his support, but the full approval expedited the time line for implementation.¹¹

Both agencies directly referenced Delta as a primary reason for their vaccination mandates. The VA argued that the mandate was necessary to protect the safety of veterans, while the DoD noted that vaccination was essential to ensure the health of the fighting force. In his initial announcement, Secretary McDonough explicitly mentioned the Delta variant as a primary reason for his decision. noting “it’s the best way to keep veterans safe, especially as the Delta variant spreads across the country.”⁴ Similarly, Secretary Austin declared, “We will also be keeping a close eye on infection rates, which are on the rise now due to the Delta variant and the impact these rates might have on our readiness.”⁵

VA and DoD leadership emphasized the safety and effectiveness of the vaccine and urged employees to voluntarily obtain the vaccine or obtain a religious or medical exemption. Those without such an exemption must adhere to masking, testing, and other restrictions.⁵ As anticipated in the earlier editorial, there has been opposition to the mandate from the workforce of the 2 agencies and their political supporters some of whom view vaccine mandates as violations of personal liberty and bodily integrity and for whom rampant disinformation has amplified entrenched distrust of the government.¹²

The decision to shift from voluntary to mandatory vaccination of federal employees responsible for the health care of veterans and the defense of citizens, which may seem draconian to some, is grounded in core public health ethical and legal principles. The first is the doctrine of the least restrictive alternative, which dictates that implemented public health policies should have the least infringement on individual liberties as possible.¹³ A corollary is that less coercive methods should be reasonably attempted before moving to more restrictive policies. Both agencies have struggled somewhat unsuccessfully to vaccinate employees even with extensive education, persuasion, and incentives. In July, the active-duty vaccination rates ranged from 58 to 77%; among VA employees it ranged from 59 to 85%, depending on the facility.¹⁴

Finally and most important, for a vaccine or other public health intervention to be ethically mandated it must have a high probability of attaining a serious purpose: here preventing the harms of sickness and death especially in the most vulnerable. In July, the White House COVID-19 Response Team reported that “preliminary data from several states over the last few months suggest that 99.5% of deaths from COVID-19 in the United States were in unvaccinated people” and were preventable.¹⁵ Ethically, even as mandates are implemented across the federal workforce, efforts to educate, encourage, and empower vaccination especially among disenfranchised cohorts must continue. But as a recently leaked CDC internal document acknowledged about the Delta Factor, “the war has changed” and so has my opinion about mandating vaccination among those upon whose service depends the life and security of us all.¹⁶

Several weeks ago, I received a call from my brother who, though not a health care professional, wanted me to know he thought the public was being too critical of scientists and physicians who “are giving us the best advice they can about COVID. People think they should have all the answers. But this virus is complicated, and they don’t always know what is going to happen next.” What makes his charitable read of the public health situation remarkable is that he is a COVID-19 survivor of one of the first reported cases of Guillain-Barre syndrome, which several expert neurologists believe is the result of COVID-19. Like so many other COVID-19 long-haul patients, he is left with lingering symptoms and residual deficits.¹

I use this personal story as the overture to this piece on why I am changing my opinion regarding a COVID-19 mandate for federal practitioners. In June I raised ethical concerns about compelling vaccination especially for service members of color based on a current and historical climate of mistrust and discrimination in health care that compulsory vaccination could exacerbate.² Instead, I followed the lead of Secretary of Defense J. Lloyd Austin III and advocated continued education and encouragement for vaccine-hesitant troops.³ So in 2 months what has so radically changed to lead Secretary Austin and US Department of Veterans Affairs (VA) Secretary Denis R. McDonough to mandate vaccination for their workforce?^4,5

I am calling the change the Delta Factor. This is not to be confused with the spy-thrillers that ironically involved rescuing a scientist! The Delta Factor is a catch-all phrase to cover the protean public health impacts of the devastating COVID-19 Delta variant now ravaging the country. Depending on the area of the country as of mid-August, the Centers for Disease Control and Prevention (CDC) estimated that 80% to > 90% of new cases were the Delta variant.⁶ An increasing number of these cases sadly are in children.⁷

According to the CDC, the Delta variant is more than twice as contagious as index or subsequent strains: making it about as contagious as chicken pox. The unvaccinated are the most susceptible to Delta and may develop more serious illness and risk of death than with other strains. Those who are fully vaccinated can still contract the virus although usually with milder cases. More worrisome is that individuals with these breakthrough infections have the same viral load as those without vaccinations, rendering them vectors of transmission, although for a shorter time than unvaccinated persons.⁸

The VA first mandated vaccination among its health care employees in July and then expanded it to all staff in August.⁹ The US Department of Defense (DoD) mandatory vaccination was announced prior to US Food and Drug Administration’s (FDA) full approval of the Pfizer-BioNTech vaccine.¹⁰ Secretary Austin asked President Biden to grant a waiver to permit mandatory vaccination even without full FDA approval, and Biden has indicated his support, but the full approval expedited the time line for implementation.¹¹

Both agencies directly referenced Delta as a primary reason for their vaccination mandates. The VA argued that the mandate was necessary to protect the safety of veterans, while the DoD noted that vaccination was essential to ensure the health of the fighting force. In his initial announcement, Secretary McDonough explicitly mentioned the Delta variant as a primary reason for his decision. noting “it’s the best way to keep veterans safe, especially as the Delta variant spreads across the country.”⁴ Similarly, Secretary Austin declared, “We will also be keeping a close eye on infection rates, which are on the rise now due to the Delta variant and the impact these rates might have on our readiness.”⁵

VA and DoD leadership emphasized the safety and effectiveness of the vaccine and urged employees to voluntarily obtain the vaccine or obtain a religious or medical exemption. Those without such an exemption must adhere to masking, testing, and other restrictions.⁵ As anticipated in the earlier editorial, there has been opposition to the mandate from the workforce of the 2 agencies and their political supporters some of whom view vaccine mandates as violations of personal liberty and bodily integrity and for whom rampant disinformation has amplified entrenched distrust of the government.¹²

The decision to shift from voluntary to mandatory vaccination of federal employees responsible for the health care of veterans and the defense of citizens, which may seem draconian to some, is grounded in core public health ethical and legal principles. The first is the doctrine of the least restrictive alternative, which dictates that implemented public health policies should have the least infringement on individual liberties as possible.¹³ A corollary is that less coercive methods should be reasonably attempted before moving to more restrictive policies. Both agencies have struggled somewhat unsuccessfully to vaccinate employees even with extensive education, persuasion, and incentives. In July, the active-duty vaccination rates ranged from 58 to 77%; among VA employees it ranged from 59 to 85%, depending on the facility.¹⁴

Finally and most important, for a vaccine or other public health intervention to be ethically mandated it must have a high probability of attaining a serious purpose: here preventing the harms of sickness and death especially in the most vulnerable. In July, the White House COVID-19 Response Team reported that “preliminary data from several states over the last few months suggest that 99.5% of deaths from COVID-19 in the United States were in unvaccinated people” and were preventable.¹⁵ Ethically, even as mandates are implemented across the federal workforce, efforts to educate, encourage, and empower vaccination especially among disenfranchised cohorts must continue. But as a recently leaked CDC internal document acknowledged about the Delta Factor, “the war has changed” and so has my opinion about mandating vaccination among those upon whose service depends the life and security of us all.¹⁶