Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: In patients with early multiple sclerosis (MS), depressive symptoms are linked to cognitive multitasking.

Major finding: Depressive symptoms in early MS cohort had a stronger association with cognitive multitasking (R² = 0.125) than with traditional monotasking procedures, including a SPEED composite variable (R² = 0.079; P less than .001).

Study details: RADIEMS was a cohort study on 185 patients with MS diagnosed in less than or equal to 5 years.

Disclosures: The study was funded by the U.S. Department of Health and Human Services, National Institutes of Health, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors declared no conflicts of interest.

Source: Glukhovsky L et al. Mult Scler. 2020 Nov 16. doi: 10.1177/1352458520958359.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

Key clinical point: This meta-analysis found no significant association between multiple sclerosis and vitiligo.

Major finding: No significant association of multiple sclerosis with prevalent vitiligo was found (pooled odds ratio, 1.33; 95% confidence interval, 0.80-2.22).

Study details: A meta-analysis of 6 case-control studies including 12,930 participants.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Shen MH et al. Sci Rep. 2020 Oct 20. doi: 10.1038/s41598-020-74298-0.

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

Like most health care workers at his hospital in Lafayette, Ind., Ramesh Adhikari, MD, FHM, occasionally gets an email noting that a patient he saw later tested positive for COVID-19. He’s reminded to self-monitor for symptoms. But 10 months into the pandemic, it has become increasingly unlikely for contact tracing investigations to result in clinicians quarantining.

The very act of working in the hospital, Dr. Adhikari said, means being likely to see COVID-19 every day, whether in a known patient or an asymptomatic person who tests positive later. If hospitalists had to quarantine after every interaction with a COVID-positive person, there wouldn’t be anyone left to do their jobs.

“It’s really hard to do [contact tracing] in health care workers thoroughly because of the way we work,” Dr. Adhikari said. “It’s impossible to do it absolutely.”

In a recently updated guidance, the Centers for Disease Control and Prevention extended more leeway in contact tracing when community rates of COVID-19 surge, even allowing that contact tracing “may not be possible” in certain situations. And by defining an exposure more narrowly – health care workers are only considered “exposed” if their contact was more than 15 minutes or lacking in some form of PPE – the guidelines suggest that hospitals can rely more on universal PPE and screening protocols, as Dr. Adhikari’s hospital does, and less on extensive contact tracing to curtail viral spread.

Accordingly, while contact tracing has gotten more lax, doctors say, universal precautions – including full PPE and screening of symptoms for patients and health care workers – have become more stringent.

It’s a shift from the beginning of the pandemic. At first, CDC recommended wearing masks only during aerosol-producing procedures. Exposures were frequently reported and health care workers sent home. With more evidence in favor of stricter PPE requirements, hospitals including the one where Shyam Odeti, MD, FHM, works in Johnson City, Tenn., have adopted a universal precaution strategy – requiring masks everywhere and a gown, face shield, gloves, and N95 to enter a COVID-positive patient’s room. Thus, most exposures fall into that low-risk category.

“If I get it and am asymptomatic, I don’t think my colleagues would be exposed by any means because of these stringent policies being enforced,” said Dr. Odeti, a hospitalist who often wears a surgical mask on top of his N95 all day. “And U.S. health care is not in a state that can afford to quarantine health care workers for 14 days.”
 

Can universal PPE precautions supplant contact tracing?

The extent of contact tracing varies by hospital. Larger university and community hospitals often have infection control and occupational health teams that can do their own contact tracing, while smaller institutions can’t always spare staff. And some state health departments get involved with contact tracing of health care workers while others do not.

“I would venture to say that most hospitals are doing something in terms of contact tracing,” said Pam Falk, MPH, CIC, a member of the Association for Professionals in Infection Control and Epidemiology’s COVID-19 task force and an infection control consultant. “It kind of depends on their bandwidth.”

But there’s no longer a norm. Outside of a pandemic, with ample staffing and far fewer instances that need to be investigated, standards for contact tracing are higher, Dr. Falk said: When a patient is found to have an airborne disease such as tuberculosis, measles, mumps, or chickenpox, a hospital’s infection prevention team should investigate, confirm the diagnosis and identify everyone who was exposed. The hospital’s occupational health team assists in deciding who will likely need prophylactic treatment and if employees should be furloughed. The thoroughness of such measures has always depended on a hospital’s bandwidth.

Because PPE seems to be able to contain COVID-19 better than some of the older diseases targeted by contact tracing, universal protections may be a reasonable alternative in current circumstances, doctors said – if PPE is available.

“At the end of the day, universal source control with surgical masks – and ideally eye protection for clinicians as well – should prevent most transmissions,” said Aaron Richterman, MD, from the division of infectious diseases at the Hospital of the University of Pennsylvania, Philadelphia, who coauthored a JAMA commentary on decreased transmission rates in hospitals.

Contact tracing is still useful, though, to identify weaknesses in universal protection measures, he said.

“I don’t think it’s worth abandoning. It’s like a tool in the toolbox. All are imperfect, and none work 100% of the time,” Dr. Richterman said, but using all of them can achieve a fairly high measure of safety. Of the tools, universal masking likely works the best, he contends, so it should be the top pick for hospitals without resources to use all of the tools.

A recent incident at Brigham and Women’s Hospital in Boston is a case study in how contact tracing can work together with universal protections to identify cracks in the system, said Dr. Richterman, who worked at the hospital earlier in the pandemic.

Mass General Brigham adopted a universal masking policy for staff and patients in March 2020. Then, when the system experienced an outbreak in September, the hospital did “a very detailed public evaluation that included contact tracing and universal testing,” Dr. Richterman said. Testing even included genetic analysis of the virus to confirm which cases were hospital acquired. In the end, the hospital identified weaknesses in infection control that could be rectified, such as clinicians eating too close together.

“The approach is not to point fingers, but to say: ‘What’s wrong with the system and how do we improve?’ ” Dr. Richterman said. “To ask, why did that maskless transmission happen? Is there not enough space to eat? Are people working too many hours? It’s useful for systems to understand where transmissions are happening.”

Amith Skandhan, MD, SFHM, a hospitalist in Dothan, Ala., is comfortable without much contact tracing as long as there is universal PPE use. His hospital informs clinicians of exposures, but “basically we’re trained to treat every patient as if they had COVID,” he said, so “I feel more secure in the hospital than in the community.” Masks have become so habitual they’re like part of your regular clothing, he said – you feel incomplete if you don’t have one.

While ad hoc approaches to contact tracing may be useful in the current stage of the pandemic, they are likely to be short-lived: Once a community’s positivity rate falls, the CDC’s guidance suggests how hospitals can return to full contact tracing.

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

Like most health care workers at his hospital in Lafayette, Ind., Ramesh Adhikari, MD, FHM, occasionally gets an email noting that a patient he saw later tested positive for COVID-19. He’s reminded to self-monitor for symptoms. But 10 months into the pandemic, it has become increasingly unlikely for contact tracing investigations to result in clinicians quarantining.

The very act of working in the hospital, Dr. Adhikari said, means being likely to see COVID-19 every day, whether in a known patient or an asymptomatic person who tests positive later. If hospitalists had to quarantine after every interaction with a COVID-positive person, there wouldn’t be anyone left to do their jobs.

“It’s really hard to do [contact tracing] in health care workers thoroughly because of the way we work,” Dr. Adhikari said. “It’s impossible to do it absolutely.”

In a recently updated guidance, the Centers for Disease Control and Prevention extended more leeway in contact tracing when community rates of COVID-19 surge, even allowing that contact tracing “may not be possible” in certain situations. And by defining an exposure more narrowly – health care workers are only considered “exposed” if their contact was more than 15 minutes or lacking in some form of PPE – the guidelines suggest that hospitals can rely more on universal PPE and screening protocols, as Dr. Adhikari’s hospital does, and less on extensive contact tracing to curtail viral spread.

Accordingly, while contact tracing has gotten more lax, doctors say, universal precautions – including full PPE and screening of symptoms for patients and health care workers – have become more stringent.

It’s a shift from the beginning of the pandemic. At first, CDC recommended wearing masks only during aerosol-producing procedures. Exposures were frequently reported and health care workers sent home. With more evidence in favor of stricter PPE requirements, hospitals including the one where Shyam Odeti, MD, FHM, works in Johnson City, Tenn., have adopted a universal precaution strategy – requiring masks everywhere and a gown, face shield, gloves, and N95 to enter a COVID-positive patient’s room. Thus, most exposures fall into that low-risk category.

“If I get it and am asymptomatic, I don’t think my colleagues would be exposed by any means because of these stringent policies being enforced,” said Dr. Odeti, a hospitalist who often wears a surgical mask on top of his N95 all day. “And U.S. health care is not in a state that can afford to quarantine health care workers for 14 days.”
 

Can universal PPE precautions supplant contact tracing?

The extent of contact tracing varies by hospital. Larger university and community hospitals often have infection control and occupational health teams that can do their own contact tracing, while smaller institutions can’t always spare staff. And some state health departments get involved with contact tracing of health care workers while others do not.

“I would venture to say that most hospitals are doing something in terms of contact tracing,” said Pam Falk, MPH, CIC, a member of the Association for Professionals in Infection Control and Epidemiology’s COVID-19 task force and an infection control consultant. “It kind of depends on their bandwidth.”

But there’s no longer a norm. Outside of a pandemic, with ample staffing and far fewer instances that need to be investigated, standards for contact tracing are higher, Dr. Falk said: When a patient is found to have an airborne disease such as tuberculosis, measles, mumps, or chickenpox, a hospital’s infection prevention team should investigate, confirm the diagnosis and identify everyone who was exposed. The hospital’s occupational health team assists in deciding who will likely need prophylactic treatment and if employees should be furloughed. The thoroughness of such measures has always depended on a hospital’s bandwidth.

Because PPE seems to be able to contain COVID-19 better than some of the older diseases targeted by contact tracing, universal protections may be a reasonable alternative in current circumstances, doctors said – if PPE is available.

“At the end of the day, universal source control with surgical masks – and ideally eye protection for clinicians as well – should prevent most transmissions,” said Aaron Richterman, MD, from the division of infectious diseases at the Hospital of the University of Pennsylvania, Philadelphia, who coauthored a JAMA commentary on decreased transmission rates in hospitals.

Contact tracing is still useful, though, to identify weaknesses in universal protection measures, he said.

“I don’t think it’s worth abandoning. It’s like a tool in the toolbox. All are imperfect, and none work 100% of the time,” Dr. Richterman said, but using all of them can achieve a fairly high measure of safety. Of the tools, universal masking likely works the best, he contends, so it should be the top pick for hospitals without resources to use all of the tools.

A recent incident at Brigham and Women’s Hospital in Boston is a case study in how contact tracing can work together with universal protections to identify cracks in the system, said Dr. Richterman, who worked at the hospital earlier in the pandemic.

Mass General Brigham adopted a universal masking policy for staff and patients in March 2020. Then, when the system experienced an outbreak in September, the hospital did “a very detailed public evaluation that included contact tracing and universal testing,” Dr. Richterman said. Testing even included genetic analysis of the virus to confirm which cases were hospital acquired. In the end, the hospital identified weaknesses in infection control that could be rectified, such as clinicians eating too close together.

“The approach is not to point fingers, but to say: ‘What’s wrong with the system and how do we improve?’ ” Dr. Richterman said. “To ask, why did that maskless transmission happen? Is there not enough space to eat? Are people working too many hours? It’s useful for systems to understand where transmissions are happening.”

Amith Skandhan, MD, SFHM, a hospitalist in Dothan, Ala., is comfortable without much contact tracing as long as there is universal PPE use. His hospital informs clinicians of exposures, but “basically we’re trained to treat every patient as if they had COVID,” he said, so “I feel more secure in the hospital than in the community.” Masks have become so habitual they’re like part of your regular clothing, he said – you feel incomplete if you don’t have one.

While ad hoc approaches to contact tracing may be useful in the current stage of the pandemic, they are likely to be short-lived: Once a community’s positivity rate falls, the CDC’s guidance suggests how hospitals can return to full contact tracing.

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

Like most health care workers at his hospital in Lafayette, Ind., Ramesh Adhikari, MD, FHM, occasionally gets an email noting that a patient he saw later tested positive for COVID-19. He’s reminded to self-monitor for symptoms. But 10 months into the pandemic, it has become increasingly unlikely for contact tracing investigations to result in clinicians quarantining.

The very act of working in the hospital, Dr. Adhikari said, means being likely to see COVID-19 every day, whether in a known patient or an asymptomatic person who tests positive later. If hospitalists had to quarantine after every interaction with a COVID-positive person, there wouldn’t be anyone left to do their jobs.

“It’s really hard to do [contact tracing] in health care workers thoroughly because of the way we work,” Dr. Adhikari said. “It’s impossible to do it absolutely.”

In a recently updated guidance, the Centers for Disease Control and Prevention extended more leeway in contact tracing when community rates of COVID-19 surge, even allowing that contact tracing “may not be possible” in certain situations. And by defining an exposure more narrowly – health care workers are only considered “exposed” if their contact was more than 15 minutes or lacking in some form of PPE – the guidelines suggest that hospitals can rely more on universal PPE and screening protocols, as Dr. Adhikari’s hospital does, and less on extensive contact tracing to curtail viral spread.

Accordingly, while contact tracing has gotten more lax, doctors say, universal precautions – including full PPE and screening of symptoms for patients and health care workers – have become more stringent.

It’s a shift from the beginning of the pandemic. At first, CDC recommended wearing masks only during aerosol-producing procedures. Exposures were frequently reported and health care workers sent home. With more evidence in favor of stricter PPE requirements, hospitals including the one where Shyam Odeti, MD, FHM, works in Johnson City, Tenn., have adopted a universal precaution strategy – requiring masks everywhere and a gown, face shield, gloves, and N95 to enter a COVID-positive patient’s room. Thus, most exposures fall into that low-risk category.

“If I get it and am asymptomatic, I don’t think my colleagues would be exposed by any means because of these stringent policies being enforced,” said Dr. Odeti, a hospitalist who often wears a surgical mask on top of his N95 all day. “And U.S. health care is not in a state that can afford to quarantine health care workers for 14 days.”
 

Can universal PPE precautions supplant contact tracing?

The extent of contact tracing varies by hospital. Larger university and community hospitals often have infection control and occupational health teams that can do their own contact tracing, while smaller institutions can’t always spare staff. And some state health departments get involved with contact tracing of health care workers while others do not.

“I would venture to say that most hospitals are doing something in terms of contact tracing,” said Pam Falk, MPH, CIC, a member of the Association for Professionals in Infection Control and Epidemiology’s COVID-19 task force and an infection control consultant. “It kind of depends on their bandwidth.”

But there’s no longer a norm. Outside of a pandemic, with ample staffing and far fewer instances that need to be investigated, standards for contact tracing are higher, Dr. Falk said: When a patient is found to have an airborne disease such as tuberculosis, measles, mumps, or chickenpox, a hospital’s infection prevention team should investigate, confirm the diagnosis and identify everyone who was exposed. The hospital’s occupational health team assists in deciding who will likely need prophylactic treatment and if employees should be furloughed. The thoroughness of such measures has always depended on a hospital’s bandwidth.

Because PPE seems to be able to contain COVID-19 better than some of the older diseases targeted by contact tracing, universal protections may be a reasonable alternative in current circumstances, doctors said – if PPE is available.

“At the end of the day, universal source control with surgical masks – and ideally eye protection for clinicians as well – should prevent most transmissions,” said Aaron Richterman, MD, from the division of infectious diseases at the Hospital of the University of Pennsylvania, Philadelphia, who coauthored a JAMA commentary on decreased transmission rates in hospitals.

Contact tracing is still useful, though, to identify weaknesses in universal protection measures, he said.

“I don’t think it’s worth abandoning. It’s like a tool in the toolbox. All are imperfect, and none work 100% of the time,” Dr. Richterman said, but using all of them can achieve a fairly high measure of safety. Of the tools, universal masking likely works the best, he contends, so it should be the top pick for hospitals without resources to use all of the tools.

A recent incident at Brigham and Women’s Hospital in Boston is a case study in how contact tracing can work together with universal protections to identify cracks in the system, said Dr. Richterman, who worked at the hospital earlier in the pandemic.

Mass General Brigham adopted a universal masking policy for staff and patients in March 2020. Then, when the system experienced an outbreak in September, the hospital did “a very detailed public evaluation that included contact tracing and universal testing,” Dr. Richterman said. Testing even included genetic analysis of the virus to confirm which cases were hospital acquired. In the end, the hospital identified weaknesses in infection control that could be rectified, such as clinicians eating too close together.

“The approach is not to point fingers, but to say: ‘What’s wrong with the system and how do we improve?’ ” Dr. Richterman said. “To ask, why did that maskless transmission happen? Is there not enough space to eat? Are people working too many hours? It’s useful for systems to understand where transmissions are happening.”

Amith Skandhan, MD, SFHM, a hospitalist in Dothan, Ala., is comfortable without much contact tracing as long as there is universal PPE use. His hospital informs clinicians of exposures, but “basically we’re trained to treat every patient as if they had COVID,” he said, so “I feel more secure in the hospital than in the community.” Masks have become so habitual they’re like part of your regular clothing, he said – you feel incomplete if you don’t have one.

While ad hoc approaches to contact tracing may be useful in the current stage of the pandemic, they are likely to be short-lived: Once a community’s positivity rate falls, the CDC’s guidance suggests how hospitals can return to full contact tracing.

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

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

The U.S. Food and Drug Administration has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Roughly 40% of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), which causes inflammation in the kidneys and can lead to end-stage kidney disease.

“Benlysta is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease,” Hal Barron, MD, GlaxoSmithKline’s chief scientific officer and president of research and development, said in a company news release.

Belimumab IV infusion was first approved in the United States in March 2011 for adults with SLE. The FDA approved belimumab IV infusion for use in children as young as age 5 years with SLE in 2019.

Both the IV and subcutaneous formulations are now indicated in the United States for adults with SLE and LN.

Belimumab is a B-lymphocyte stimulator protein inhibitor that is thought to decrease the amount of abnormal B cells; the latter are thought to play a role in lupus.

The expanded indication for belimumab for patients with LN is based on findings from the BLISS-LN phase 3 trial, published in The New England Journal of Medicine in September.

“Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys” represents a “compelling therapeutic approach to lupus nephritis,” the lead investigator of BLISS-LN, Richard Furie, MD, told the online annual Perspectives in Rheumatic Diseases meeting recently.

“In the 4 decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis, and despite all of our efforts, 10%-30% of patients with lupus kidney disease still progress to end-stage kidney disease,” Dr. Furie, who is chief of the division of rheumatology at Northwell Health, notes in the GSK statement.

“The data from the BLISS-LN study show that Benlysta added to standard therapy not only increased response rates over 2 years, but it also prevented worsening of kidney disease in patients with active lupus nephritis, compared to standard therapy alone,” he added.

BLISS-LN study: Belimumab effect seen mostly in those on MMF

BLISS-LN enrolled 448 adults with biopsy-confirmed active LN. Half were randomly allocated to receive IV belimumab (10 mg/kg) plus standard therapy (mycophenolate mofetil for induction and maintenance or cyclophosphamide for induction followed by azathioprine for maintenance, with steroids) and half to receive placebo plus standard therapy.

At 2 years, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval, 1.0- 2.3; P = .03).

This primary endpoint was defined as a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate that was no worse than 20% below the value before the renal flare or ≥60 mL per minute per 1.73 m² of body surface area, without use of rescue therapy.

The risk for a renal-related event or death was also significantly lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; P = .001). The safety profile of belimumab was consistent with that observed in prior studies.

But in a commentary that accompanied the publication of BLISS-LN, editorialists noted that “most of the treatment effect was seen in patients who had received mycophenolate mofetil. No benefit was present in the subgroup of patients who received cyclophosphamide-azathioprine.”

In addition, induction treatment was not randomly assigned, editorialists Michael Ward, MD, MPH, and Maria Tektonidou, MD, PhD, noted.

“If patients with more severe nephritis were preferentially treated with cyclophosphamide, a likely inclination among most physicians, the trial may be telling us that belimumab enhances responses only among less severely affected patients,” observed Dr. Ward, who is with the National Institutes of Health, and Dr. Tektonidou, of the National and Kopodistrian University, in Athens.

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

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

A Food and Drug Administration advisory committee lit a long-standing fuse, recommending that evidence from the controversial TOPCAT trial can be used to support a new indication for spironolactone.

The generic aldosterone blocker is already approved for the treatment of heart failure with reduced ejection fraction (HFrEF). 

Hopes that it could be the first therapy to show improved outcomes in HF with preserved EF (HFpEF) were dashed in 2013 when TOPCAT failed to show a significant benefit over placebo for the primary endpoint of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest.

Regional differences in the data, however, aroused concerns about the findings early on. Patients enrolled in Russia and the Republic of Georgia were younger, less likely to qualify on the basis of elevated natriuretic peptide levels, and had more evidence of ischemic heart disease than those in the Americas.

Event rates were also substantially lower in Russia/Georgia than in the Americas and in previous HFpEF trials, suggesting that many of these patients may not have had heart failure, the trialists argued.

In the Americas, results for the primary endpoint favor spironolactone over placebo (10.4 vs. 12.6 events per 100 patient-years; P = .026), whereas the rate in Russia/Georgia was much lower than in the Americas and slightly favors placebo (2.5 vs. 2.3 events/100 patient-years).

Medication noncompliance also may have been more common in Russia/Georgia based on pharmacodynamic studies and a 2017 analysis showing undetectable levels of canrenone, an active metabolite of spironolactone, in 30% of Russian versus 3% of North American patients who reported using the drug at 1 year.

TOPCAT investigator Marc Pfeffer, MD, PhD, from Brigham and Women’s Hospital and Harvard Medical School, Boston, said no trial is without flaws but that the observations represent serious misconduct. “Really we’re talking about a cancer, a cancer that has clear margins. The margins are Russia, Georgia that warrant censoring their data.”

The FDA’s own review of the National Institutes of Health–sponsored study, however, showed no significant interaction between treatment and region (P = .12) and “insufficient evidence to conclude the two regions are different enough such that overall results should not be considered,” said FDA statistician Ququan Liu, MD, MS.

She cautioned against removing data from a whole region that constituted almost half the study population and said it would set a precedent on what is considered substantial evidence for approval.

Several advisors concurred but, ultimately, the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 4, with 1 abstention, that TOPCAT provides “sufficient evidence to support any indication.”

The same committee voted yesterday in support of an expanded role for sacubitril/valsartan (Entresto, Novartis) in select patients with HFpEF. In casting a “no” vote, panelist Steven E. Nissen, MD, from the Cleveland Clinic, said that decisions made by the panel set precedent.

Catherine Hackett

“If the pharmaceutical industry came to us with a study like this and said the P value was .14 but we think a bunch of our sites weren’t very good and so we’re going to throw those data out and just look at the sites we like, the FDA would not have even brought that before us,” he said. “I cannot hold other sponsors, including our own government, to a different standard.”

Dr. Nissen argued that the primary endpoint failed by a significant margin (P = .138), the study was marginally powered, there was a troubling amount of missing data in the two regions, and spironolactone is also not without side effects. “Poor study conduct cannot be an excuse for a result we don’t like.”

Panel chair Julia B. Lewis, MD, from Vanderbilt University Medical Center in Nashville, Tenn., said she would love to support a cheap, generic drug to keep HF patients out of the hospital but was troubled by the egregious conduct of the trial and concerns about cherry-picking results. “My heart says this would be a great place for us to go but I can’t say that my head thinks this is an acceptable body of data.”

Several panelists, however, highlighted the benefits with spironolactone over placebo in the Americas including an 18% reduction in hospitalization for HF (21% vs. 25%; hazard ratio, 0.82; P = .04) and a 25% reduction in cumulative HF hospitalizations (361 vs. 438 events; incidence rate ratio, 0.75; P = .024).

There was also a reduction in CV mortality with spironolactone (11% vs. 14%; HR, 0.74; P = .027) – something, it was noted, not observed during the prior day’s proceeding on sacubitril/valsartan.

Panelist Christopher M. O’Connor, MD, from Inova Heart and Vascular Institute in Falls Church, Va., and Duke University, Durham, N.C., said he voted “yes” because of the totality of the information and that the investigators provided “compelling evidence” with or without the Russia/Georgia cohort on the efficacy on HF hospitalization reduction. “I think this is the augmented sweet spot of this data set.”

C. Michael Gibson, MD, said his decision to vote yes was not based on analyses that excluded half the patients but rather on the totality of the evidence, particularly the benefit on cumulative HF hospitalizations and in those with an EF lower than 56%.

Several panelists and members of the public cited for treatments among patients with HFpEF. Edward K. Kasper, MD, from Johns Hopkins University, Baltimore, said he found both sides of the argument persuasive but that he already uses spironolactone in this setting. “Somehow I’ve become convinced that this drug worked, so I voted yes.”

Dr. Kasper said the FDA may ultimately find there isn’t an indication for spironolactone in HFpEF but that it will likely move from a IIb to IIa recommendation in the next iteration of the American College of Cardiology guidelines.

Paul Ridker, MD, MPH, from Brigham and Women’s Hospital and Harvard Medical School, said he shared concerns about the precedent of dropping half the data, “even though, in this case, I believe half the data is wrong.”

Dr. Ridker noted that he would have been comfortable using the secondary endpoint of HF reduction as an indication in patients with mildly reduced EF but abstained because that data was not presented today, although it may be available from TOPCAT and the RALES trial.

The panel took up other nonvoting questions, including what additional data would be needed to augment support for approval. Suggestions ranged from additional analyses to a new trial, with TOPCAT serving as “pilot data,” but no recommendation was made.

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

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

aotto@mdedge.com

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Fellowship is a time of great growth for pediatric hospital medicine fellows as clinicians, educators, scholars, and as leaders. Leadership is a crucial skill for hospitalists that is cultivated throughout fellowship. As fellows, we step into the role of clinical team leader for the first time and it is our responsibility to create a clinical and educational environment that is safe, inviting and engaging.

For possibly the first time in our careers, pediatric hospital medicine fellows are expected to make final decisions, big and small. We are faced with high-pressure situations almost daily, whether it is a rapid response on a patient, tough diagnostic and therapeutic decisions, difficult conversations with families, or dealing with challenging team members.

Soon after starting fellowship I was faced with a such a situation. The patient was a 6-month-old infant with trisomy 21 who was admitted because of feeding difficulties. They were working on oral feeds but required nasogastric (NG) feeds to meet caloric needs. On my first day on service, the residents indicated that the medical team desired the patient to have a gastrostomy tube (G-tube) placed. I was hoping to send the patient home for a few weeks with the NG tube to see if they were making progress on their oral feeds before deciding on the need for a G-tube. However, the patient’s parents pulled me aside in the hallway and said they were considering a third possibility.

The parents felt strongly about a trial period of a few weeks without the NG tube to see if the patient was able to maintain adequate weight gain with just oral feeds. The bedside nurse reiterated that the family felt their concerns had not been considered up until this point. As the fellow and team leader, it was my job to navigate between my resident team, myself, and the family in order to make a final decision. Through a bedside meeting and shared decision making, we were able to compromise and negotiate a decision, allowing the patient to go home on just oral feeds with close follow-up with their pediatrician. Afterwards, I found myself searching for strategies to be a better leader in these situations.

I found a potential answer in a recent article from the Harvard Business Review titled “What Aircraft Crews Know About Managing High-Pressure Situations.”¹ The article discusses crew resource management (CRM), which was developed in the 1980s and is used in civil and military aviation worldwide. CRM is based on two principles to improve crisis management: The hierarchy on the flight deck must be flattened, and crew members must be actively integrated into the flight’s work flows and decision-making processes.

The authors of the article conducted two different studies to further understand CRM and its effects. The first study included observing 11 flight crews in emergency simulations. In the study, the flight crew had to react to an emergency, and then conduct a landing of the aircraft. What the authors found was that the captain’s style of communication had a major impact on crew performance in two major ways: Crews performed consistently better under times of pressure when the copilot was included in the decision-making process, and captains who asked open-ended questions (“How do you assess the situation”) came up with better solutions than captains who asked “yes or no” questions.

The authors conclude that “involving colleagues as equal decision partners by asking them questions…aids constructive, factual information exchange.” The second study consisted of conducting 61 interviews with flight crew members to better understand crisis management. In the interviews, the same theme occurred, that open-ended questions are vital in all decision-making processes and may be preventative against dangerous or imperfect outcomes. As fellows and team leaders we can learn from CRM and these studies. We need to flatten the hierarchy and ask open-ended questions.

To flatten the hierarchy, we should value the thoughts and opinions of all our team members. Now more than ever in this current COVID-19 pandemic with many hospitals instituting telehealth/telerounding for some or all team members, it is essential to utilize our entire “flight crew” (physicians, nurses, therapists, subspecialists, social worker, case managers, etc.) during routine decisions and high-stake decisions. We should make sure our flight crew, especially the bedside nurse is part of the decision-making process.² This means we need to ensure they are present and given a voice on clinical rounds. To flatten the hierarchy, we must take pride in eliciting other team member’s opinions. We must realize that we alone do not have all the answers, and other team members may have different frameworks in which they process a decision.

Finally, in medicine, our patients and families are included in our flight crew. They too must have a voice in the decision-making process. Previous studies have shown that patients and families desire to be included in the decision-making process, and opportunities exist to improve shared decision-making in pediatrics.^3-5 Lastly, we should commit to asking open-ended questions from our team and our patients. We should value their input and use their answers and frameworks to make the best decision for our patients.

I wasn’t aware at the time, but I was using some of the principles of CRM while navigating my high-pressure situation. A bedside meeting with all team members and the patient’s family helped to flatten the hierarchy by understanding and valuing each team member’s input. Asking open-ended questions of the different team members led to a more inviting and engaging clinical and learning environment. These strategies helped to lead our team into a clinical decision that wasn’t entirely clear at first but ended up being the best decision for the patient, as they are now thriving without ever requiring supplemental nutrition after discharge.

As physicians, we have learned a lot from the airline industry about wellness and the effect of fatigue on performance. It is clear now that we can also learn from them about clinical decision-making and leadership strategies. When adopted for health care, CRM principles have been shown to result in a culture of safety and long-term behavioral change.^6,7 If we can model ourselves after the airline industry by following the principles of CRM, then we will be better clinicians, educators, and leaders.

Dr. Palmer is a second-year pediatric hospital medicine fellow at Children’s Hospital Los Angeles and is working toward a masters in academic medicine at the University of Southern California, Los Angeles, with a focus on curriculum development and educational scholarship production.

References

1. Hagan J et al. What Aircraft Crews Know About Managing High-Pressure Situations. Harvard Business Review. 2019 Dec. https://hbr.org/2019/12/what-aircraft-crews-know-about-managing-high-pressure-situations

2. Erickson J. Bedside nurse involvement in end-of-life decision-making: A brief review of the literature. Dimens Crit Care Nurs. 2013;32(2):65-8.

3. Richards CA et al. Physicians perceptions of shared decision-making in neonatal and pediatric critical care. Am J Hosp Palliat Care. 2018;35(4):669-76.

4. Boland L et al. Barriers and facilitators of pediatric shared decision-making: A systematic review. Implement Sci. 2019 Jan 18. doi: 10.1186/s13012-018-0851-5.

5. Blankenburg R et al. Shared decision-making during inpatient rounds: Opportunities for improvement in patient engagement and communication. J Hosp Med. 2018;13(7):453-61.

6. Kemper PF et al. Crew resource management training in the intensive care unit. A multisite controlled before-after study. BMJ Qual Saf. 2016;25(8):577-87.

7. Sax HC et al. Can aviation-based team training elicit sustainable behavioral change? Arch Surg. 2009;144(12):1133-7.

Fellowship is a time of great growth for pediatric hospital medicine fellows as clinicians, educators, scholars, and as leaders. Leadership is a crucial skill for hospitalists that is cultivated throughout fellowship. As fellows, we step into the role of clinical team leader for the first time and it is our responsibility to create a clinical and educational environment that is safe, inviting and engaging.

For possibly the first time in our careers, pediatric hospital medicine fellows are expected to make final decisions, big and small. We are faced with high-pressure situations almost daily, whether it is a rapid response on a patient, tough diagnostic and therapeutic decisions, difficult conversations with families, or dealing with challenging team members.

Soon after starting fellowship I was faced with a such a situation. The patient was a 6-month-old infant with trisomy 21 who was admitted because of feeding difficulties. They were working on oral feeds but required nasogastric (NG) feeds to meet caloric needs. On my first day on service, the residents indicated that the medical team desired the patient to have a gastrostomy tube (G-tube) placed. I was hoping to send the patient home for a few weeks with the NG tube to see if they were making progress on their oral feeds before deciding on the need for a G-tube. However, the patient’s parents pulled me aside in the hallway and said they were considering a third possibility.

The parents felt strongly about a trial period of a few weeks without the NG tube to see if the patient was able to maintain adequate weight gain with just oral feeds. The bedside nurse reiterated that the family felt their concerns had not been considered up until this point. As the fellow and team leader, it was my job to navigate between my resident team, myself, and the family in order to make a final decision. Through a bedside meeting and shared decision making, we were able to compromise and negotiate a decision, allowing the patient to go home on just oral feeds with close follow-up with their pediatrician. Afterwards, I found myself searching for strategies to be a better leader in these situations.

I found a potential answer in a recent article from the Harvard Business Review titled “What Aircraft Crews Know About Managing High-Pressure Situations.”¹ The article discusses crew resource management (CRM), which was developed in the 1980s and is used in civil and military aviation worldwide. CRM is based on two principles to improve crisis management: The hierarchy on the flight deck must be flattened, and crew members must be actively integrated into the flight’s work flows and decision-making processes.

The authors of the article conducted two different studies to further understand CRM and its effects. The first study included observing 11 flight crews in emergency simulations. In the study, the flight crew had to react to an emergency, and then conduct a landing of the aircraft. What the authors found was that the captain’s style of communication had a major impact on crew performance in two major ways: Crews performed consistently better under times of pressure when the copilot was included in the decision-making process, and captains who asked open-ended questions (“How do you assess the situation”) came up with better solutions than captains who asked “yes or no” questions.

The authors conclude that “involving colleagues as equal decision partners by asking them questions…aids constructive, factual information exchange.” The second study consisted of conducting 61 interviews with flight crew members to better understand crisis management. In the interviews, the same theme occurred, that open-ended questions are vital in all decision-making processes and may be preventative against dangerous or imperfect outcomes. As fellows and team leaders we can learn from CRM and these studies. We need to flatten the hierarchy and ask open-ended questions.

To flatten the hierarchy, we should value the thoughts and opinions of all our team members. Now more than ever in this current COVID-19 pandemic with many hospitals instituting telehealth/telerounding for some or all team members, it is essential to utilize our entire “flight crew” (physicians, nurses, therapists, subspecialists, social worker, case managers, etc.) during routine decisions and high-stake decisions. We should make sure our flight crew, especially the bedside nurse is part of the decision-making process.² This means we need to ensure they are present and given a voice on clinical rounds. To flatten the hierarchy, we must take pride in eliciting other team member’s opinions. We must realize that we alone do not have all the answers, and other team members may have different frameworks in which they process a decision.

Finally, in medicine, our patients and families are included in our flight crew. They too must have a voice in the decision-making process. Previous studies have shown that patients and families desire to be included in the decision-making process, and opportunities exist to improve shared decision-making in pediatrics.^3-5 Lastly, we should commit to asking open-ended questions from our team and our patients. We should value their input and use their answers and frameworks to make the best decision for our patients.

I wasn’t aware at the time, but I was using some of the principles of CRM while navigating my high-pressure situation. A bedside meeting with all team members and the patient’s family helped to flatten the hierarchy by understanding and valuing each team member’s input. Asking open-ended questions of the different team members led to a more inviting and engaging clinical and learning environment. These strategies helped to lead our team into a clinical decision that wasn’t entirely clear at first but ended up being the best decision for the patient, as they are now thriving without ever requiring supplemental nutrition after discharge.

As physicians, we have learned a lot from the airline industry about wellness and the effect of fatigue on performance. It is clear now that we can also learn from them about clinical decision-making and leadership strategies. When adopted for health care, CRM principles have been shown to result in a culture of safety and long-term behavioral change.^6,7 If we can model ourselves after the airline industry by following the principles of CRM, then we will be better clinicians, educators, and leaders.

Dr. Palmer is a second-year pediatric hospital medicine fellow at Children’s Hospital Los Angeles and is working toward a masters in academic medicine at the University of Southern California, Los Angeles, with a focus on curriculum development and educational scholarship production.

References

1. Hagan J et al. What Aircraft Crews Know About Managing High-Pressure Situations. Harvard Business Review. 2019 Dec. https://hbr.org/2019/12/what-aircraft-crews-know-about-managing-high-pressure-situations

2. Erickson J. Bedside nurse involvement in end-of-life decision-making: A brief review of the literature. Dimens Crit Care Nurs. 2013;32(2):65-8.

3. Richards CA et al. Physicians perceptions of shared decision-making in neonatal and pediatric critical care. Am J Hosp Palliat Care. 2018;35(4):669-76.

4. Boland L et al. Barriers and facilitators of pediatric shared decision-making: A systematic review. Implement Sci. 2019 Jan 18. doi: 10.1186/s13012-018-0851-5.

5. Blankenburg R et al. Shared decision-making during inpatient rounds: Opportunities for improvement in patient engagement and communication. J Hosp Med. 2018;13(7):453-61.

6. Kemper PF et al. Crew resource management training in the intensive care unit. A multisite controlled before-after study. BMJ Qual Saf. 2016;25(8):577-87.

7. Sax HC et al. Can aviation-based team training elicit sustainable behavioral change? Arch Surg. 2009;144(12):1133-7.

Fellowship is a time of great growth for pediatric hospital medicine fellows as clinicians, educators, scholars, and as leaders. Leadership is a crucial skill for hospitalists that is cultivated throughout fellowship. As fellows, we step into the role of clinical team leader for the first time and it is our responsibility to create a clinical and educational environment that is safe, inviting and engaging.

For possibly the first time in our careers, pediatric hospital medicine fellows are expected to make final decisions, big and small. We are faced with high-pressure situations almost daily, whether it is a rapid response on a patient, tough diagnostic and therapeutic decisions, difficult conversations with families, or dealing with challenging team members.

Soon after starting fellowship I was faced with a such a situation. The patient was a 6-month-old infant with trisomy 21 who was admitted because of feeding difficulties. They were working on oral feeds but required nasogastric (NG) feeds to meet caloric needs. On my first day on service, the residents indicated that the medical team desired the patient to have a gastrostomy tube (G-tube) placed. I was hoping to send the patient home for a few weeks with the NG tube to see if they were making progress on their oral feeds before deciding on the need for a G-tube. However, the patient’s parents pulled me aside in the hallway and said they were considering a third possibility.

The parents felt strongly about a trial period of a few weeks without the NG tube to see if the patient was able to maintain adequate weight gain with just oral feeds. The bedside nurse reiterated that the family felt their concerns had not been considered up until this point. As the fellow and team leader, it was my job to navigate between my resident team, myself, and the family in order to make a final decision. Through a bedside meeting and shared decision making, we were able to compromise and negotiate a decision, allowing the patient to go home on just oral feeds with close follow-up with their pediatrician. Afterwards, I found myself searching for strategies to be a better leader in these situations.

I found a potential answer in a recent article from the Harvard Business Review titled “What Aircraft Crews Know About Managing High-Pressure Situations.”¹ The article discusses crew resource management (CRM), which was developed in the 1980s and is used in civil and military aviation worldwide. CRM is based on two principles to improve crisis management: The hierarchy on the flight deck must be flattened, and crew members must be actively integrated into the flight’s work flows and decision-making processes.

The authors of the article conducted two different studies to further understand CRM and its effects. The first study included observing 11 flight crews in emergency simulations. In the study, the flight crew had to react to an emergency, and then conduct a landing of the aircraft. What the authors found was that the captain’s style of communication had a major impact on crew performance in two major ways: Crews performed consistently better under times of pressure when the copilot was included in the decision-making process, and captains who asked open-ended questions (“How do you assess the situation”) came up with better solutions than captains who asked “yes or no” questions.

The authors conclude that “involving colleagues as equal decision partners by asking them questions…aids constructive, factual information exchange.” The second study consisted of conducting 61 interviews with flight crew members to better understand crisis management. In the interviews, the same theme occurred, that open-ended questions are vital in all decision-making processes and may be preventative against dangerous or imperfect outcomes. As fellows and team leaders we can learn from CRM and these studies. We need to flatten the hierarchy and ask open-ended questions.

To flatten the hierarchy, we should value the thoughts and opinions of all our team members. Now more than ever in this current COVID-19 pandemic with many hospitals instituting telehealth/telerounding for some or all team members, it is essential to utilize our entire “flight crew” (physicians, nurses, therapists, subspecialists, social worker, case managers, etc.) during routine decisions and high-stake decisions. We should make sure our flight crew, especially the bedside nurse is part of the decision-making process.² This means we need to ensure they are present and given a voice on clinical rounds. To flatten the hierarchy, we must take pride in eliciting other team member’s opinions. We must realize that we alone do not have all the answers, and other team members may have different frameworks in which they process a decision.

Finally, in medicine, our patients and families are included in our flight crew. They too must have a voice in the decision-making process. Previous studies have shown that patients and families desire to be included in the decision-making process, and opportunities exist to improve shared decision-making in pediatrics.^3-5 Lastly, we should commit to asking open-ended questions from our team and our patients. We should value their input and use their answers and frameworks to make the best decision for our patients.

I wasn’t aware at the time, but I was using some of the principles of CRM while navigating my high-pressure situation. A bedside meeting with all team members and the patient’s family helped to flatten the hierarchy by understanding and valuing each team member’s input. Asking open-ended questions of the different team members led to a more inviting and engaging clinical and learning environment. These strategies helped to lead our team into a clinical decision that wasn’t entirely clear at first but ended up being the best decision for the patient, as they are now thriving without ever requiring supplemental nutrition after discharge.

As physicians, we have learned a lot from the airline industry about wellness and the effect of fatigue on performance. It is clear now that we can also learn from them about clinical decision-making and leadership strategies. When adopted for health care, CRM principles have been shown to result in a culture of safety and long-term behavioral change.^6,7 If we can model ourselves after the airline industry by following the principles of CRM, then we will be better clinicians, educators, and leaders.

Dr. Palmer is a second-year pediatric hospital medicine fellow at Children’s Hospital Los Angeles and is working toward a masters in academic medicine at the University of Southern California, Los Angeles, with a focus on curriculum development and educational scholarship production.

References

1. Hagan J et al. What Aircraft Crews Know About Managing High-Pressure Situations. Harvard Business Review. 2019 Dec. https://hbr.org/2019/12/what-aircraft-crews-know-about-managing-high-pressure-situations

2. Erickson J. Bedside nurse involvement in end-of-life decision-making: A brief review of the literature. Dimens Crit Care Nurs. 2013;32(2):65-8.

3. Richards CA et al. Physicians perceptions of shared decision-making in neonatal and pediatric critical care. Am J Hosp Palliat Care. 2018;35(4):669-76.

4. Boland L et al. Barriers and facilitators of pediatric shared decision-making: A systematic review. Implement Sci. 2019 Jan 18. doi: 10.1186/s13012-018-0851-5.

5. Blankenburg R et al. Shared decision-making during inpatient rounds: Opportunities for improvement in patient engagement and communication. J Hosp Med. 2018;13(7):453-61.

6. Kemper PF et al. Crew resource management training in the intensive care unit. A multisite controlled before-after study. BMJ Qual Saf. 2016;25(8):577-87.

7. Sax HC et al. Can aviation-based team training elicit sustainable behavioral change? Arch Surg. 2009;144(12):1133-7.

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The 16 million–plus people in the United States, and 72 million worldwide, who have been infected with COVID-19 – and survived – are likely asking themselves the same questions: Am I immune now? Is it over or do I have to brace myself for the possibility of a reinfection? Moreover, could the second time potentially be worse than the first?

I was diagnosed with COVID in March of this year. After spending 10 days in the hospital, and one night in the ICU, it took another 2 months for the air-hunger, headaches, and fatigue to completely resolve. Compared with many other unfortunate victims, I did all right – and I am very grateful for the care I received.

Now, as the surge in cases takes new life, I will be on the front lines taking care of patients. Having had an eventful personal encounter with the virus, I now have a unique vantage point and remain fully committed to paying my fortunate circumstances forward. Although I can’t help but have the same question faced by millions of others: Am I safe now?

It is no surprise that studies have shown health care workers comprising 6% of COVID hospital admissions, with one-third of these admissions being nurses. Recently, we heard that over 900 health care workers at Mayo Clinic had acquired the infection in the first 2 weeks of the ongoing second COVID surge. Are these frontline workers protected? Can they return to work with no fear of a rerun? Or, for that matter, anyone who has been afflicted by COVID – are they now forever immune?

There are no clear answers here. But to understand this a little, let’s quickly revisit some basic principles of immunity.
 

Innate and adaptive immunity

Simply put, there are two forms of immunity: innate and adaptive. Innate immunity encompasses our body’s natural protective mechanisms that come into play almost immediately. This enables recognition of the virus and activates an immediate antiviral defense and attempt at removal of the infective agent. This, however, does not always do the job. Accordingly, a couple weeks after the initial exposure to the pathogen, adaptive immunity is invoked. Circulating white blood cells within our body recognize the virus and set off an immune response, involving the activation of T and B cells that actively attack the infective agent. It is this T- and B-cell–mediated immunity that should protect one against a second infection with the same agent.

What about herd immunity?

Herd immunity is defined as essentially yielding to the virus and letting it spread naturally in order to develop community-wide immunity. By consequence of a large proportion of the population becoming immune after exposure to the disease, person-to-person spread can potentially be mitigated. This does not confer immunity to the virus at the individual level; rather, it reduces the risk of vulnerable people coming in contact with the pathogen.

Unfortunately, depending on herd immunity as a way to deal with COVID-19 has not worked well, even in well-contained countries like Sweden, where a disproportionate number of their most vulnerable populations have died. It is self-evident that containment strategies with vaccination may be our best way forward to achieve herd immunity. Not surrendering to the virus.
 

Am I safe from reinfection?

In all honesty, we’re not entirely sure. But it is important to recognize a few points when considering your relative safety.

• The immune system is far from perfect. Not everyone has a robust immune response. And in those who do, the immune response can wane over time, potentially allowing for reinfection. While rare, there have already been some clearly documented reinfections, four that have been confirmed and published; two patients (in Nevada and Ecuador) actually fared worse the second time around.
• The virus can mutate and escape detection by the immune system. One could still be susceptible to reinfection from a different strain. (At least, this remains the case with the influenza virus.) There is some evidence that SARS-CoV-2 does not mutate rapidly, and hence this may not be a problem. But we don’t know for certain, at least as of yet.
• Even a vigorous immune response can be overwhelmed by the virus. It is unclear whether the relative length of time and the amount of virus exposure could undermine a previously primed immune system.

A prior infection and a consequent healthy immunity may help you combat a reinfection but it does not prevent you from harboring or carrying the virus. You may be asymptomatic, but you can still be a carrier and spread the infection. I am a strong advocate for limiting your exposure to others no matter your previous exposure status, in order to limit the spread of the virus.
 

So, what should I do?

I guess the answer is that you can’t be too careful. Not everyone has had their antibody levels tested, and even if positive, it is unclear how well that affords protection. It is best to presume that you are vulnerable for a reinfection and that you can still carry and spread the virus. This may be the safest approach until we actually achieve herd immunity through vaccination.

Even then, for a period of time, there will remain a sense of uncertainty. So, containment strategies inclusive of distancing and masking will and should remain a way of life at least until mid-2021, when we will be in a better position to reassess the landscape.

The surge is back. As I repay my debt and get back to the front line, I will continue to mask up and practice distancing. I am taking no chances of getting reinfected or being an asymptomatic carrier.

I had COVID, I also have antibodies, and I will be taking the vaccine. I implore you all to do the same.

Jag Singh is a physician, scientist, and professor at Harvard. He is passionate about social issues, leadership, digital health, and medical innovations. You can follow him on Twitter @JagSinghMD.

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

The acute rash with minute pustules and associated leukocytosis with neutrophilia and eosinophilia led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), which may have been triggered by azithromycin—the patient’s only recent medication. AGEP is a severe cutaneous eruption that may be associated with systemic involvement. Medications are usually implicated, and patients often seek urgent evaluation.

AGEP typically begins as an acute eruption in the intertriginous sites of the axilla, groin, and neck, but often becomes more generalized. The diagnosis is strongly suggested by the condition’s key features: fever (97% of cases) and leukocytosis (87%) with neutrophilia (91%) and eosinophilia (30%). Leukocytosis peaks 4 days after pustulosis occurs and lasts for about 12 days. Although common, fever is not always documented in patients with AGEP. (This patient was a case in point.)

In approximately 90% of AGEP cases, medications such as antibiotics and calcium channel blockers are implicated; however, the lack of such an association does not preclude the diagnosis. In cases of drug reactions, the eruption typically develops 1 to 2 days after a medication is begun, and the pustules typically resolve in fewer than 15 days. In 17% of patients, systemic involvement can occur and can include the liver, kidneys, bone marrow, and lungs. A physical exam, review of systems, and a laboratory evaluation can help rule out systemic involvement and guide additional testing.

AGEP has an incidence of 1 to 5 cases per million people per year, affecting women slightly more frequently than men. While the pathophysiology is not well understood, AGEP and its differential diagnoses are categorized as T cell-related inflammatory responses.

There are at least 4 severe cutaneous eruptions that might be confused with AGEP, all of which may be associated with fever. They include a drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and pustular psoriasis. The clinical features that may help differentiate these conditions from AGEP include timeline, mucocutaneous features, organ system involvement, and histopathologic findings.

Patients who have AGEP, including those with systemic involvement, generally improve after the offending drug is discontinued and treatment with topical corticosteroids is initiated. A brief course of systemic corticosteroids can also be considered for patients with severe skin involvement or systemic involvement.

This patient was prescribed topical corticosteroid wet dressing treatments twice daily for 2 weeks. At the 2-week follow-up visit, the rash had completely cleared and only minimal residual erythema was noted. The patient was instructed to avoid azithromycin.

This case was adapted from: Tolkachjov SN, Wetter DA, Sandefur BJ. Generalized pustular eruption. J Fam Pract. 2018;67:309-310,312.

The acute rash with minute pustules and associated leukocytosis with neutrophilia and eosinophilia led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), which may have been triggered by azithromycin—the patient’s only recent medication. AGEP is a severe cutaneous eruption that may be associated with systemic involvement. Medications are usually implicated, and patients often seek urgent evaluation.

AGEP typically begins as an acute eruption in the intertriginous sites of the axilla, groin, and neck, but often becomes more generalized. The diagnosis is strongly suggested by the condition’s key features: fever (97% of cases) and leukocytosis (87%) with neutrophilia (91%) and eosinophilia (30%). Leukocytosis peaks 4 days after pustulosis occurs and lasts for about 12 days. Although common, fever is not always documented in patients with AGEP. (This patient was a case in point.)

In approximately 90% of AGEP cases, medications such as antibiotics and calcium channel blockers are implicated; however, the lack of such an association does not preclude the diagnosis. In cases of drug reactions, the eruption typically develops 1 to 2 days after a medication is begun, and the pustules typically resolve in fewer than 15 days. In 17% of patients, systemic involvement can occur and can include the liver, kidneys, bone marrow, and lungs. A physical exam, review of systems, and a laboratory evaluation can help rule out systemic involvement and guide additional testing.

AGEP has an incidence of 1 to 5 cases per million people per year, affecting women slightly more frequently than men. While the pathophysiology is not well understood, AGEP and its differential diagnoses are categorized as T cell-related inflammatory responses.

There are at least 4 severe cutaneous eruptions that might be confused with AGEP, all of which may be associated with fever. They include a drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and pustular psoriasis. The clinical features that may help differentiate these conditions from AGEP include timeline, mucocutaneous features, organ system involvement, and histopathologic findings.

Patients who have AGEP, including those with systemic involvement, generally improve after the offending drug is discontinued and treatment with topical corticosteroids is initiated. A brief course of systemic corticosteroids can also be considered for patients with severe skin involvement or systemic involvement.

This patient was prescribed topical corticosteroid wet dressing treatments twice daily for 2 weeks. At the 2-week follow-up visit, the rash had completely cleared and only minimal residual erythema was noted. The patient was instructed to avoid azithromycin.

This case was adapted from: Tolkachjov SN, Wetter DA, Sandefur BJ. Generalized pustular eruption. J Fam Pract. 2018;67:309-310,312.

The acute rash with minute pustules and associated leukocytosis with neutrophilia and eosinophilia led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), which may have been triggered by azithromycin—the patient’s only recent medication. AGEP is a severe cutaneous eruption that may be associated with systemic involvement. Medications are usually implicated, and patients often seek urgent evaluation.

AGEP typically begins as an acute eruption in the intertriginous sites of the axilla, groin, and neck, but often becomes more generalized. The diagnosis is strongly suggested by the condition’s key features: fever (97% of cases) and leukocytosis (87%) with neutrophilia (91%) and eosinophilia (30%). Leukocytosis peaks 4 days after pustulosis occurs and lasts for about 12 days. Although common, fever is not always documented in patients with AGEP. (This patient was a case in point.)

In approximately 90% of AGEP cases, medications such as antibiotics and calcium channel blockers are implicated; however, the lack of such an association does not preclude the diagnosis. In cases of drug reactions, the eruption typically develops 1 to 2 days after a medication is begun, and the pustules typically resolve in fewer than 15 days. In 17% of patients, systemic involvement can occur and can include the liver, kidneys, bone marrow, and lungs. A physical exam, review of systems, and a laboratory evaluation can help rule out systemic involvement and guide additional testing.

AGEP has an incidence of 1 to 5 cases per million people per year, affecting women slightly more frequently than men. While the pathophysiology is not well understood, AGEP and its differential diagnoses are categorized as T cell-related inflammatory responses.

There are at least 4 severe cutaneous eruptions that might be confused with AGEP, all of which may be associated with fever. They include a drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and pustular psoriasis. The clinical features that may help differentiate these conditions from AGEP include timeline, mucocutaneous features, organ system involvement, and histopathologic findings.

Patients who have AGEP, including those with systemic involvement, generally improve after the offending drug is discontinued and treatment with topical corticosteroids is initiated. A brief course of systemic corticosteroids can also be considered for patients with severe skin involvement or systemic involvement.

This patient was prescribed topical corticosteroid wet dressing treatments twice daily for 2 weeks. At the 2-week follow-up visit, the rash had completely cleared and only minimal residual erythema was noted. The patient was instructed to avoid azithromycin.

This case was adapted from: Tolkachjov SN, Wetter DA, Sandefur BJ. Generalized pustular eruption. J Fam Pract. 2018;67:309-310,312.