MDedge Neurology

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

A COVID-19 outbreak has occurred at one of the most remote places on earth – the Princess Elisabeth Polar Station in Antarctica.

Two-thirds of the 25 workers have tested positive at the station, despite all of them being fully vaccinated and going through several testing stages before being allowed entrance, the Belgium publication Le Soir reported.

So far, all the cases are mild at the station, which is owned by Belgium and operated by a private group: the International Polar Foundation.

The first case was discovered Dec. 14 among a group that arrived a week earlier in Antarctica, Le Soir reported. The first three people to test positive evacuated Dec. 23, Le Soir said, but the virus continued to spread among the remaining workers at the base.

Le Soir, citing a virologist, said the Omicron variant probably caused the outbreak, because the crew made its last stop in South Africa before arriving in Antarctica.

New arrivals to the station have been put on hold until the outbreak is brought under control, and one of the missions planned for the base has been postponed, Le Soir said.

“The situation isn’t dramatic,” Joseph Cheek, a project manager for the International Polar Foundation, told the BBC. “While it has been an inconvenience to have to quarantine certain members of the staff who caught the virus, it hasn’t significantly affected our work at the station overall.”

The BBC said there was another COVID outbreak in Antarctica about a year ago at the Bernardo O’Higgins research station operated by Chile.

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

A COVID-19 outbreak has occurred at one of the most remote places on earth – the Princess Elisabeth Polar Station in Antarctica.

Two-thirds of the 25 workers have tested positive at the station, despite all of them being fully vaccinated and going through several testing stages before being allowed entrance, the Belgium publication Le Soir reported.

So far, all the cases are mild at the station, which is owned by Belgium and operated by a private group: the International Polar Foundation.

The first case was discovered Dec. 14 among a group that arrived a week earlier in Antarctica, Le Soir reported. The first three people to test positive evacuated Dec. 23, Le Soir said, but the virus continued to spread among the remaining workers at the base.

Le Soir, citing a virologist, said the Omicron variant probably caused the outbreak, because the crew made its last stop in South Africa before arriving in Antarctica.

New arrivals to the station have been put on hold until the outbreak is brought under control, and one of the missions planned for the base has been postponed, Le Soir said.

“The situation isn’t dramatic,” Joseph Cheek, a project manager for the International Polar Foundation, told the BBC. “While it has been an inconvenience to have to quarantine certain members of the staff who caught the virus, it hasn’t significantly affected our work at the station overall.”

The BBC said there was another COVID outbreak in Antarctica about a year ago at the Bernardo O’Higgins research station operated by Chile.

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

A COVID-19 outbreak has occurred at one of the most remote places on earth – the Princess Elisabeth Polar Station in Antarctica.

Two-thirds of the 25 workers have tested positive at the station, despite all of them being fully vaccinated and going through several testing stages before being allowed entrance, the Belgium publication Le Soir reported.

So far, all the cases are mild at the station, which is owned by Belgium and operated by a private group: the International Polar Foundation.

The first case was discovered Dec. 14 among a group that arrived a week earlier in Antarctica, Le Soir reported. The first three people to test positive evacuated Dec. 23, Le Soir said, but the virus continued to spread among the remaining workers at the base.

Le Soir, citing a virologist, said the Omicron variant probably caused the outbreak, because the crew made its last stop in South Africa before arriving in Antarctica.

New arrivals to the station have been put on hold until the outbreak is brought under control, and one of the missions planned for the base has been postponed, Le Soir said.

“The situation isn’t dramatic,” Joseph Cheek, a project manager for the International Polar Foundation, told the BBC. “While it has been an inconvenience to have to quarantine certain members of the staff who caught the virus, it hasn’t significantly affected our work at the station overall.”

The BBC said there was another COVID outbreak in Antarctica about a year ago at the Bernardo O’Higgins research station operated by Chile.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

“I am capable and ready to begin.”

Sounds trite, doesn’t it? What slush pile did that come from?

Actually, it was the closing sentence of the 1988 “personal statement” I wrote for my medical school applications. (I applied to something like 25 schools, maybe more.) Come to think of it, I suspect my father came up with that line.

Have you read your personal statement since you became an attending? It’s like a letter from an alternate universe, where you weren’t a doctor, weren’t sure you’d ever be one, and were trying very hard to sound confident in the face of an uncertain future.

Mine began in a melodramatic way, emphasizing what I’d seen as an emergency department volunteer. When I wrote it I thought I’d be an ED doc, and never imagined that years later I’d be doing something entirely different – and loving it.

Having the opportunity to go back and talk to our younger selves is a common trope in movies, but in real life reading something like this is as close as it gets. But it’s still neat. It brings back not who you are, but who you were. Reminds you why you wanted to be a doctor, when you were younger, probably more naive, and felt medicine was a calling, not a job.

Do you still feel that way, after years of paperwork, insurance games, a mortgage, a family, defensive medicine, your own health changes, and all the other things life and the often-jaded medical field bring?

I hope the answer is still yes.

On my first day at Creighton Medical School, our dean – the late William L. Pancoe, PhD – gave us a “go get ‘em!” speech. His main theme was that we should “wear sneakers and hit the ground running” on day 1, because otherwise we’d never catch up. But he also told us to remember and hold on to the feeling we had when we got our first medical school acceptance letter. That feeling of relief, joy, the realization that we’d been given a chance to make our dream come true. He told us that feeling might be all that would get us through the long nights of studying, the occasional failures, the self-doubts, and all the other things in the 4 years to come.

Dean Pancoe, you were absolutely right. Today I’m older than you were when you gave us that speech. My only additions would be:

1. Don’t just hold onto that feeling for medical school, but for life.

2. Always keep one copy of your personal statement (even if in your picture you were wearing hideous 1980s-style glasses, like mine). Keep it in your work desk, not in the bottom of a filing cabinet or scrapbook. Read it at least once a year. It’ll take maybe 2 minutes. You have that much time to spare.

Because it’s not just the young who can learn from the wisdom of the old. The older can learn, and be reminded of, many good things from the young. Even if that younger person is you.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“I am capable and ready to begin.”

Sounds trite, doesn’t it? What slush pile did that come from?

Actually, it was the closing sentence of the 1988 “personal statement” I wrote for my medical school applications. (I applied to something like 25 schools, maybe more.) Come to think of it, I suspect my father came up with that line.

Have you read your personal statement since you became an attending? It’s like a letter from an alternate universe, where you weren’t a doctor, weren’t sure you’d ever be one, and were trying very hard to sound confident in the face of an uncertain future.

Mine began in a melodramatic way, emphasizing what I’d seen as an emergency department volunteer. When I wrote it I thought I’d be an ED doc, and never imagined that years later I’d be doing something entirely different – and loving it.

Having the opportunity to go back and talk to our younger selves is a common trope in movies, but in real life reading something like this is as close as it gets. But it’s still neat. It brings back not who you are, but who you were. Reminds you why you wanted to be a doctor, when you were younger, probably more naive, and felt medicine was a calling, not a job.

Do you still feel that way, after years of paperwork, insurance games, a mortgage, a family, defensive medicine, your own health changes, and all the other things life and the often-jaded medical field bring?

I hope the answer is still yes.

On my first day at Creighton Medical School, our dean – the late William L. Pancoe, PhD – gave us a “go get ‘em!” speech. His main theme was that we should “wear sneakers and hit the ground running” on day 1, because otherwise we’d never catch up. But he also told us to remember and hold on to the feeling we had when we got our first medical school acceptance letter. That feeling of relief, joy, the realization that we’d been given a chance to make our dream come true. He told us that feeling might be all that would get us through the long nights of studying, the occasional failures, the self-doubts, and all the other things in the 4 years to come.

Dean Pancoe, you were absolutely right. Today I’m older than you were when you gave us that speech. My only additions would be:

1. Don’t just hold onto that feeling for medical school, but for life.

2. Always keep one copy of your personal statement (even if in your picture you were wearing hideous 1980s-style glasses, like mine). Keep it in your work desk, not in the bottom of a filing cabinet or scrapbook. Read it at least once a year. It’ll take maybe 2 minutes. You have that much time to spare.

Because it’s not just the young who can learn from the wisdom of the old. The older can learn, and be reminded of, many good things from the young. Even if that younger person is you.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“I am capable and ready to begin.”

Sounds trite, doesn’t it? What slush pile did that come from?

Actually, it was the closing sentence of the 1988 “personal statement” I wrote for my medical school applications. (I applied to something like 25 schools, maybe more.) Come to think of it, I suspect my father came up with that line.

Have you read your personal statement since you became an attending? It’s like a letter from an alternate universe, where you weren’t a doctor, weren’t sure you’d ever be one, and were trying very hard to sound confident in the face of an uncertain future.

Mine began in a melodramatic way, emphasizing what I’d seen as an emergency department volunteer. When I wrote it I thought I’d be an ED doc, and never imagined that years later I’d be doing something entirely different – and loving it.

Having the opportunity to go back and talk to our younger selves is a common trope in movies, but in real life reading something like this is as close as it gets. But it’s still neat. It brings back not who you are, but who you were. Reminds you why you wanted to be a doctor, when you were younger, probably more naive, and felt medicine was a calling, not a job.

Do you still feel that way, after years of paperwork, insurance games, a mortgage, a family, defensive medicine, your own health changes, and all the other things life and the often-jaded medical field bring?

I hope the answer is still yes.

On my first day at Creighton Medical School, our dean – the late William L. Pancoe, PhD – gave us a “go get ‘em!” speech. His main theme was that we should “wear sneakers and hit the ground running” on day 1, because otherwise we’d never catch up. But he also told us to remember and hold on to the feeling we had when we got our first medical school acceptance letter. That feeling of relief, joy, the realization that we’d been given a chance to make our dream come true. He told us that feeling might be all that would get us through the long nights of studying, the occasional failures, the self-doubts, and all the other things in the 4 years to come.

Dean Pancoe, you were absolutely right. Today I’m older than you were when you gave us that speech. My only additions would be:

1. Don’t just hold onto that feeling for medical school, but for life.

2. Always keep one copy of your personal statement (even if in your picture you were wearing hideous 1980s-style glasses, like mine). Keep it in your work desk, not in the bottom of a filing cabinet or scrapbook. Read it at least once a year. It’ll take maybe 2 minutes. You have that much time to spare.

Because it’s not just the young who can learn from the wisdom of the old. The older can learn, and be reminded of, many good things from the young. Even if that younger person is you.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

As the United States enters a third year of the COVID-19 pandemic, case numbers are higher than ever and disrupting businesses, travel plans, and school schedules.

The United States is reporting a 7-day average of more than 386,000 cases after several record-breaking days, according to the data tracker by the New York Times. The United States surpassed 585,000 cases on Dec. 30, setting a new record before the New Year’s holiday.

New York, Washington, D.C., and other states along the East Coast are leading the national surge. New York reported more than 85,000 new cases on the last day of 2021, marking the highest 1-day total in the state since the pandemic began.

“As we fight the winter surge, we need to keep the most vulnerable among us in mind – do what you can to keep others in your community safe from COVID-19,” New York Gov. Kathy Hochul said in a statement on Jan. 1, 2022.

“Wear a mask, wash your hands, and take advantage of the best tool we have at our disposal – the vaccine,” she said.

The 2021 winter surge in the United States peaked around Jan. 12, which may suggest that the country has a week or so before the current wave reaches its height and begins to drop, the newspaper reported.

In the meantime, people are dealing with disruptions as they return from holiday travel and begin the new year. Airlines canceled more than 2,700 flights on Jan. 1 and more than 1,900 flights on Jan. 2, bringing the total since Christmas Eve to more than 14,000 canceled flights.

About half of cancellations were connected to wintry weather at key airline hubs in Chicago and Denver, the newspaper reported, as well as ongoing flight crew shortages caused by the Omicron variant.

More disruptions could continue, the Federal Aviation Administration warned, as an increasing number of its air-traffic control employees test positive for COVID-19.

“To maintain safety, traffic volumes at some facilities could be reduced, which might result in delays during busy periods,” an FAA spokesman told The Wall Street Journal.

The current COVID-19 surge will also affect businesses and schools as the new year begins. A growing number of universities are opting to start the next semester with remote instruction.

American University, Duke University, and Michigan State University announced in recent days that they would delay in-person classes to slow the spread of the coronavirus on campus. They will begin classes online on Jan. 10 and return to campus the following week or later.

“I realize that students prefer to be in person, and so do I. But it is important that we do so in a safe manner,” Samuel Stanley Jr., MD, president of Michigan State University, said in a statement on New Year’s Eve.

K-12 school districts are deciding how to adapt as well. Some districts are bringing back mask requirements, and some are ramping up testing. Others are moving to remote learning – and signaling the need for flexibility as the Omicron variant brings new surprises.

“Change has been the only constant in this fight,” Roger Leon, the superintendent for Newark (N.J.) Public Schools, wrote in a note to parents. He announced on Dec. 30, 2021, that students would learn remotely for at least the first 2 weeks of the new year.

This continues “to be a brutal, relentless, and ruthless virus that rears its ugly head at inopportune times,” he said.

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

As the United States enters a third year of the COVID-19 pandemic, case numbers are higher than ever and disrupting businesses, travel plans, and school schedules.

The United States is reporting a 7-day average of more than 386,000 cases after several record-breaking days, according to the data tracker by the New York Times. The United States surpassed 585,000 cases on Dec. 30, setting a new record before the New Year’s holiday.

New York, Washington, D.C., and other states along the East Coast are leading the national surge. New York reported more than 85,000 new cases on the last day of 2021, marking the highest 1-day total in the state since the pandemic began.

“As we fight the winter surge, we need to keep the most vulnerable among us in mind – do what you can to keep others in your community safe from COVID-19,” New York Gov. Kathy Hochul said in a statement on Jan. 1, 2022.

“Wear a mask, wash your hands, and take advantage of the best tool we have at our disposal – the vaccine,” she said.

The 2021 winter surge in the United States peaked around Jan. 12, which may suggest that the country has a week or so before the current wave reaches its height and begins to drop, the newspaper reported.

In the meantime, people are dealing with disruptions as they return from holiday travel and begin the new year. Airlines canceled more than 2,700 flights on Jan. 1 and more than 1,900 flights on Jan. 2, bringing the total since Christmas Eve to more than 14,000 canceled flights.

About half of cancellations were connected to wintry weather at key airline hubs in Chicago and Denver, the newspaper reported, as well as ongoing flight crew shortages caused by the Omicron variant.

More disruptions could continue, the Federal Aviation Administration warned, as an increasing number of its air-traffic control employees test positive for COVID-19.

“To maintain safety, traffic volumes at some facilities could be reduced, which might result in delays during busy periods,” an FAA spokesman told The Wall Street Journal.

The current COVID-19 surge will also affect businesses and schools as the new year begins. A growing number of universities are opting to start the next semester with remote instruction.

American University, Duke University, and Michigan State University announced in recent days that they would delay in-person classes to slow the spread of the coronavirus on campus. They will begin classes online on Jan. 10 and return to campus the following week or later.

“I realize that students prefer to be in person, and so do I. But it is important that we do so in a safe manner,” Samuel Stanley Jr., MD, president of Michigan State University, said in a statement on New Year’s Eve.

K-12 school districts are deciding how to adapt as well. Some districts are bringing back mask requirements, and some are ramping up testing. Others are moving to remote learning – and signaling the need for flexibility as the Omicron variant brings new surprises.

“Change has been the only constant in this fight,” Roger Leon, the superintendent for Newark (N.J.) Public Schools, wrote in a note to parents. He announced on Dec. 30, 2021, that students would learn remotely for at least the first 2 weeks of the new year.

This continues “to be a brutal, relentless, and ruthless virus that rears its ugly head at inopportune times,” he said.

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

As the United States enters a third year of the COVID-19 pandemic, case numbers are higher than ever and disrupting businesses, travel plans, and school schedules.

The United States is reporting a 7-day average of more than 386,000 cases after several record-breaking days, according to the data tracker by the New York Times. The United States surpassed 585,000 cases on Dec. 30, setting a new record before the New Year’s holiday.

New York, Washington, D.C., and other states along the East Coast are leading the national surge. New York reported more than 85,000 new cases on the last day of 2021, marking the highest 1-day total in the state since the pandemic began.

“As we fight the winter surge, we need to keep the most vulnerable among us in mind – do what you can to keep others in your community safe from COVID-19,” New York Gov. Kathy Hochul said in a statement on Jan. 1, 2022.

“Wear a mask, wash your hands, and take advantage of the best tool we have at our disposal – the vaccine,” she said.

The 2021 winter surge in the United States peaked around Jan. 12, which may suggest that the country has a week or so before the current wave reaches its height and begins to drop, the newspaper reported.

In the meantime, people are dealing with disruptions as they return from holiday travel and begin the new year. Airlines canceled more than 2,700 flights on Jan. 1 and more than 1,900 flights on Jan. 2, bringing the total since Christmas Eve to more than 14,000 canceled flights.

About half of cancellations were connected to wintry weather at key airline hubs in Chicago and Denver, the newspaper reported, as well as ongoing flight crew shortages caused by the Omicron variant.

More disruptions could continue, the Federal Aviation Administration warned, as an increasing number of its air-traffic control employees test positive for COVID-19.

“To maintain safety, traffic volumes at some facilities could be reduced, which might result in delays during busy periods,” an FAA spokesman told The Wall Street Journal.

The current COVID-19 surge will also affect businesses and schools as the new year begins. A growing number of universities are opting to start the next semester with remote instruction.

American University, Duke University, and Michigan State University announced in recent days that they would delay in-person classes to slow the spread of the coronavirus on campus. They will begin classes online on Jan. 10 and return to campus the following week or later.

“I realize that students prefer to be in person, and so do I. But it is important that we do so in a safe manner,” Samuel Stanley Jr., MD, president of Michigan State University, said in a statement on New Year’s Eve.

K-12 school districts are deciding how to adapt as well. Some districts are bringing back mask requirements, and some are ramping up testing. Others are moving to remote learning – and signaling the need for flexibility as the Omicron variant brings new surprises.

“Change has been the only constant in this fight,” Roger Leon, the superintendent for Newark (N.J.) Public Schools, wrote in a note to parents. He announced on Dec. 30, 2021, that students would learn remotely for at least the first 2 weeks of the new year.

This continues “to be a brutal, relentless, and ruthless virus that rears its ugly head at inopportune times,” he said.

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

Federal officials will allow some flexibility in meeting new requirements on covering the costs of clinical trials for people enrolled in Medicaid, seeking to accommodate states where legislatures will not meet in time to make needed changes in rules.

Congress in 2020 ordered U.S. states to have their Medicaid programs cover expenses related to participation in certain clinical trials, a move that was hailed by the American Society of Clinical Oncology (ASCO) and other groups as a boost to trials as well as to patients with serious illness who have lower incomes.

The mandate went into effect on Jan. 1, but the Centers for Medicare & Medicaid Services will allow accommodations in terms of implementation time for states that have not yet been able to make needed legislative changes, Daniel Tsai, deputy administrator and director of the Center for Medicaid and CHIP Services, wrote in a Dec. 7 letter. Mr. Tsai’s letter doesn’t mention specific states. The CMS did not immediately respond to a request seeking information on the states expected to apply for waivers.

Medicaid has in recent years been a rare large U.S. insurance program that does not cover the costs of clinical trials. The Affordable Care Act of 2010 mandated this coverage for people in private insurance plans. The federal government in 2000 decided that Medicare would do so.

‘A hidden opportunity’

A perspective article last May in the New England Journal of Medicine referred to the new Medicaid mandate on clinical trials as a “hidden opportunity,” referring to its genesis as an add-on in a massive federal spending package enacted in December 2020.

In the article, Samuel U. Takvorian, MD, MSHP, of the University of Pennsylvania, Philadelphia, and coauthors noted that rates of participation in clinical trials remain low for racial and ethnic minority groups, due in part to the lack of Medicaid coverage.

“For example, non-Hispanic White patients are nearly twice as likely as Black patients and three times as likely as Hispanic patients to enroll in cancer clinical trials – a gap that has widened over time,” Dr. Takvorian and coauthors wrote. “Inequities in enrollment have also manifested during the COVID-19 pandemic, which has disproportionately affected non-White patients, without their commensurate representation in trials of COVID-19 therapeutics.”

In October, researchers from the Arthur G. James Cancer Hospital and Ohio State University, Columbus, published results of a retrospective study of patients with stage I-IV pancreatic cancer that also found inequities in enrollment. Mariam F. Eskander, MD, MPH, and coauthors reported what they found by examining records for 1,127 patients (0.4%) enrolled in clinical trials and 301,340 (99.6%) who did not enroll. They found that enrollment in trials increased over the study period, but not for Black patients or patients on Medicaid.

In an interview, Dr. Eskander said the new Medicaid policy will remove a major obstacle to participation in clinical trials. An oncologist, Dr. Eskander said she is looking forward to being able to help more of her patients get access to experimental medicines and treatments.

But that may not be enough to draw more people with low incomes into these studies, said Dr. Eskander, who is now at Rutgers Cancer Institute of New Jersey in New Brunswick. She urges greater use of patient navigators to help people on Medicaid understand the resources available to them, as well as broad use of Medicaid’s nonemergency medical transportation (NEMT) benefit.

“Some patients will be offered clinical trial enrollment and some will accept, but I really worry about the challenges low-income people face with things like transportation and getting time off work,” she said.

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

Federal officials will allow some flexibility in meeting new requirements on covering the costs of clinical trials for people enrolled in Medicaid, seeking to accommodate states where legislatures will not meet in time to make needed changes in rules.

Congress in 2020 ordered U.S. states to have their Medicaid programs cover expenses related to participation in certain clinical trials, a move that was hailed by the American Society of Clinical Oncology (ASCO) and other groups as a boost to trials as well as to patients with serious illness who have lower incomes.

The mandate went into effect on Jan. 1, but the Centers for Medicare & Medicaid Services will allow accommodations in terms of implementation time for states that have not yet been able to make needed legislative changes, Daniel Tsai, deputy administrator and director of the Center for Medicaid and CHIP Services, wrote in a Dec. 7 letter. Mr. Tsai’s letter doesn’t mention specific states. The CMS did not immediately respond to a request seeking information on the states expected to apply for waivers.

Medicaid has in recent years been a rare large U.S. insurance program that does not cover the costs of clinical trials. The Affordable Care Act of 2010 mandated this coverage for people in private insurance plans. The federal government in 2000 decided that Medicare would do so.

‘A hidden opportunity’

A perspective article last May in the New England Journal of Medicine referred to the new Medicaid mandate on clinical trials as a “hidden opportunity,” referring to its genesis as an add-on in a massive federal spending package enacted in December 2020.

In the article, Samuel U. Takvorian, MD, MSHP, of the University of Pennsylvania, Philadelphia, and coauthors noted that rates of participation in clinical trials remain low for racial and ethnic minority groups, due in part to the lack of Medicaid coverage.

“For example, non-Hispanic White patients are nearly twice as likely as Black patients and three times as likely as Hispanic patients to enroll in cancer clinical trials – a gap that has widened over time,” Dr. Takvorian and coauthors wrote. “Inequities in enrollment have also manifested during the COVID-19 pandemic, which has disproportionately affected non-White patients, without their commensurate representation in trials of COVID-19 therapeutics.”

In October, researchers from the Arthur G. James Cancer Hospital and Ohio State University, Columbus, published results of a retrospective study of patients with stage I-IV pancreatic cancer that also found inequities in enrollment. Mariam F. Eskander, MD, MPH, and coauthors reported what they found by examining records for 1,127 patients (0.4%) enrolled in clinical trials and 301,340 (99.6%) who did not enroll. They found that enrollment in trials increased over the study period, but not for Black patients or patients on Medicaid.

In an interview, Dr. Eskander said the new Medicaid policy will remove a major obstacle to participation in clinical trials. An oncologist, Dr. Eskander said she is looking forward to being able to help more of her patients get access to experimental medicines and treatments.

But that may not be enough to draw more people with low incomes into these studies, said Dr. Eskander, who is now at Rutgers Cancer Institute of New Jersey in New Brunswick. She urges greater use of patient navigators to help people on Medicaid understand the resources available to them, as well as broad use of Medicaid’s nonemergency medical transportation (NEMT) benefit.

“Some patients will be offered clinical trial enrollment and some will accept, but I really worry about the challenges low-income people face with things like transportation and getting time off work,” she said.

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

Federal officials will allow some flexibility in meeting new requirements on covering the costs of clinical trials for people enrolled in Medicaid, seeking to accommodate states where legislatures will not meet in time to make needed changes in rules.

Congress in 2020 ordered U.S. states to have their Medicaid programs cover expenses related to participation in certain clinical trials, a move that was hailed by the American Society of Clinical Oncology (ASCO) and other groups as a boost to trials as well as to patients with serious illness who have lower incomes.

The mandate went into effect on Jan. 1, but the Centers for Medicare & Medicaid Services will allow accommodations in terms of implementation time for states that have not yet been able to make needed legislative changes, Daniel Tsai, deputy administrator and director of the Center for Medicaid and CHIP Services, wrote in a Dec. 7 letter. Mr. Tsai’s letter doesn’t mention specific states. The CMS did not immediately respond to a request seeking information on the states expected to apply for waivers.

Medicaid has in recent years been a rare large U.S. insurance program that does not cover the costs of clinical trials. The Affordable Care Act of 2010 mandated this coverage for people in private insurance plans. The federal government in 2000 decided that Medicare would do so.

‘A hidden opportunity’

A perspective article last May in the New England Journal of Medicine referred to the new Medicaid mandate on clinical trials as a “hidden opportunity,” referring to its genesis as an add-on in a massive federal spending package enacted in December 2020.

In the article, Samuel U. Takvorian, MD, MSHP, of the University of Pennsylvania, Philadelphia, and coauthors noted that rates of participation in clinical trials remain low for racial and ethnic minority groups, due in part to the lack of Medicaid coverage.

“For example, non-Hispanic White patients are nearly twice as likely as Black patients and three times as likely as Hispanic patients to enroll in cancer clinical trials – a gap that has widened over time,” Dr. Takvorian and coauthors wrote. “Inequities in enrollment have also manifested during the COVID-19 pandemic, which has disproportionately affected non-White patients, without their commensurate representation in trials of COVID-19 therapeutics.”

In October, researchers from the Arthur G. James Cancer Hospital and Ohio State University, Columbus, published results of a retrospective study of patients with stage I-IV pancreatic cancer that also found inequities in enrollment. Mariam F. Eskander, MD, MPH, and coauthors reported what they found by examining records for 1,127 patients (0.4%) enrolled in clinical trials and 301,340 (99.6%) who did not enroll. They found that enrollment in trials increased over the study period, but not for Black patients or patients on Medicaid.

In an interview, Dr. Eskander said the new Medicaid policy will remove a major obstacle to participation in clinical trials. An oncologist, Dr. Eskander said she is looking forward to being able to help more of her patients get access to experimental medicines and treatments.

But that may not be enough to draw more people with low incomes into these studies, said Dr. Eskander, who is now at Rutgers Cancer Institute of New Jersey in New Brunswick. She urges greater use of patient navigators to help people on Medicaid understand the resources available to them, as well as broad use of Medicaid’s nonemergency medical transportation (NEMT) benefit.

“Some patients will be offered clinical trial enrollment and some will accept, but I really worry about the challenges low-income people face with things like transportation and getting time off work,” she said.

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

It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.

The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.

“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).

Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.

Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.

But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope. 

Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed. 

“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”

The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career. 

“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”

For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles. Although the term can have different definitions, a “medical miracle” generally refers to an unexpected recovery despite a dire prognosis. Frequently, the phrase has a religious connotation and is used to describe a supernatural or paranormal healing.

Do physicians believe in medical miracles? The answers are diverse.

“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
 

Disappearing cancer hailed as ‘miracle’

In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.

Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial. 

Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.

Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”

Does Dr. Ribas think the case was a medical miracle?

“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”

The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.

“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.

“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
 

Patient defies odds after 45 minutes without heartbeat

Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.

In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.

“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”

Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.

Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.

“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”

Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.

“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”

Ruby fully recovered, and 3 days later, she went home with her newborn.

While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.

However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.

“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
 

How do ‘medical miracles’ impact physicians?

When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.

“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”

Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.

“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”

In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures. 

“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”

Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.

“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
 

What to do when parents hope for a miracle

In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle. 

“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”

Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.

A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.

“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”

Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions. 

When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief. 

“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”

Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said. 

Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.

“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.

“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”

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

It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.

The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.

“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).

Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.

Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.

But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope. 

Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed. 

“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”

The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career. 

“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”

For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles. Although the term can have different definitions, a “medical miracle” generally refers to an unexpected recovery despite a dire prognosis. Frequently, the phrase has a religious connotation and is used to describe a supernatural or paranormal healing.

Do physicians believe in medical miracles? The answers are diverse.

“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
 

Disappearing cancer hailed as ‘miracle’

In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.

Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial. 

Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.

Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”

Does Dr. Ribas think the case was a medical miracle?

“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”

The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.

“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.

“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
 

Patient defies odds after 45 minutes without heartbeat

Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.

In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.

“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”

Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.

Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.

“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”

Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.

“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”

Ruby fully recovered, and 3 days later, she went home with her newborn.

While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.

However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.

“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
 

How do ‘medical miracles’ impact physicians?

When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.

“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”

Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.

“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”

In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures. 

“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”

Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.

“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
 

What to do when parents hope for a miracle

In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle. 

“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”

Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.

A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.

“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”

Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions. 

When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief. 

“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”

Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said. 

Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.

“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.

“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”

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

It was a freezing December day, and two young brothers were playing outside near a swimming pool when the younger boy, a 3-year-old toddler, fell into the water.

The 7-year-old immediately jumped into the pool to save his brother and was able to pull the toddler to the pool steps where the boy’s head was above water. But the icy temperatures overcame the older brother and he drifted underwater.

“Despite being at the forefront of medicine, what we don’t understand often exceeds what we do understand,” said Harley Rotbart, MD, author of “Miracles We Have Seen” (Health Communications: Deerfield Beach, Fla., 2016).

Paramedics arrived to find both boys unconscious and rushed them to the Children’s Hospital of Philadelphia. The younger boy regained consciousness in the ICU and recovered. The 7-year-old, however, was unresponsive and remained in a coma, said Dr. Rotbart a pediatrician and author based in Denver.

Family members stayed at the boy’s bedside and prayed. But after several weeks, the child’s condition remained unchanged. His parents began to discuss ending life support and organ donation. Then late one night, as Dr. Rotbart sat reading to the unconscious patient, the little boy squeezed his hand. In disbelief, Dr. Rotbart told all of his colleagues about the squeeze the next morning. Everyone attributed the movement to an involuntary muscle spasm, he said. After all, every test and scan showed the boy had no brain function.

But later that day, the child grasped another staff member’s hand. Shortly after that, he squeezed in response to a command. Dr. Rotbart and his staff were stunned, but cautious about feeling too much hope. 

Days later, the child opened his eyes. Then, he smiled. His parents were overjoyed. 

“When he walked out of the hospital more than 2 months after the near-drowning and his heroic rescue of his little brother, we all cheered and cried,” Dr. Rotbart wrote in his book. “We cried many times in the weeks preceding, and I still cry whenever I recall this story.”

The experience, which happened years ago when Dr. Rotbart was a trainee, has stayed with the pediatrician his entire career. 

“His awakening was seemingly impossible – and then it happened,” Dr. Rotbart said. “Despite being at the forefront of medicine and science, what we don’t understand often exceeds what we do understand. And even when we think we understand, we are frequently proven wrong.”

For many, Dr. Rotbart’s experience raises questions about the existence of medical miracles. Although the term can have different definitions, a “medical miracle” generally refers to an unexpected recovery despite a dire prognosis. Frequently, the phrase has a religious connotation and is used to describe a supernatural or paranormal healing.

Do physicians believe in medical miracles? The answers are diverse.

“I have no doubt that extraordinary outcomes happen where patients who are overwhelmingly expected not to survive, do,” says Eric Beam, MD, a hospitalist based in San Diego. “That’s one of the reasons we choose our words very carefully in our conversations with patients and their families and remember that nothing is 0%, and nothing is 100%. But doctors tend to treat situations that are 99.9% as absolute. I don’t think you can practice medicine with the hope or expectation that every case you see has the potential to beat the odds – or be a medical miracle.”
 

Disappearing cancer hailed as ‘miracle’

In 2003, physicians projected that Joseph Rick, 40, had just a few months to live. His mucosal melanoma had spread throughout his body, progressing even after several surgeries, radiation therapy, and a combination of chemotherapy agents, recalled Antoni Ribas, MD, PhD, an oncologist and director of the tumor immunology program at Jonsson Comprehensive Cancer Center in Los Angeles.

Mr. Rick’s melanoma had spread to his intestines with traces on his stomach and bladder. Tumors were present on his liver, lungs, and pancreas. Rick bought a grave and prepared for the worst, he recounted in a Cancer Research Institute video. But his fate took a turn when he enrolled in an experimental drug trial in December 2003. The phase 1 trial was for a new immune modulating antibody, called an anti–CTLA-4 antibody, said Dr. Ribas, who conducted the trial. 

Over the next few weeks and months, all areas of Rick’s melanoma metastases disappeared. By 2009, he was in remission. He has lived the rest of his life with no evidence of melanoma, according to Dr. Ribas.

Mr. Rick’s case has been referenced throughout literature and news stories as a “medical miracle” and a “cancer miracle.”

Does Dr. Ribas think the case was a medical miracle?

“The response in Joseph Rick was what happened in 10%-15% of patients who received anti-CTLA-4 therapy,” Dr. Ribas said. “These were not miracles. These patients responded because their immune system trying to attack the cancer had been stuck at the CTLA-4 checkpoint. Blocking this checkpoint allowed their immune system to proceed to attack and kill cancer cells anywhere in the body.”

The scientific basis of this therapy was work by University of Texas MD Anderson Cancer Center immunologist James Allison, PhD, that had been done 5 years earlier in mouse models, where giving an anti–CTLA-4 antibody to mice allowed them to reject several implanted cancers, Dr. Ribas explained. Dr. Allison received the 2018 Nobel Prize in Physiology or Medicine for this work, subsequently opening the door for what we now call “immune checkpoint blockade therapy for cancer.” Dr. Ribas added.

“We tend to call miracles good things that we do not understand how they happened,” Dr. Ribas said. “From the human observation perspective, there have been plenty of medical miracles. However, each one has a specific biological mechanism that led to improvement in a patient. In cancer treatment, early studies using the immune system resulted in occasional patients having tumor responses and long-term benefits.

“With the increased understanding of how the immune system interacts with cancers, which is based on remarkable progress in understanding how the immune system works generated over the past several decades, these ‘miracles’ become specific mechanisms leading to response to cancer, which can then be replicated in other patients.”
 

Patient defies odds after 45 minutes without heartbeat

Florida ob.gyn. Michael Fleischer, MD, had just performed a routine repeat cesarean birth, delivering a healthy baby girl. His patient, Ruby, had a history of high blood pressure but medication taken during the pregnancy had kept her levels stabilized.

In the waiting room, Dr. Fleischer informed Ruby’s large family of the good news. He was planning to head home early that day when he heard his name being called over the hospital’s loudspeaker. Ruby had stopped breathing.

“The anesthesiologist was with her and had immediately intubated her,” Dr. Fleischer said. “We checked to make sure there was no problems or bleeding from the C-section, but everything was completely fine. However, we couldn’t keep her blood pressure stable.”

Dr. Fleischer suspected the respiratory arrest was caused by either an amniotic fluid embolism or a pulmonary embolism. Intubation continued and physicians gave Ruby medication to stabilize her blood pressure. Then suddenly, Ruby’s heart stopped.

Dr. Fleischer and other doctors began compressions, which they continued for 30 minutes. They shocked Ruby with defibrillator paddles multiple times, but there was no change.

“I was already thinking, this is hopeless, there’s nothing we can do,” he said. “The writing is on the wall. She’s going to die.”

Dr. Fleischer spoke to Ruby’s family and explained the tragic turn of events. Relatives were distraught and tearfully visited Ruby to say their goodbyes. They prayed and cried. Eventually, physicians ceased compressions. Ruby had gone 45 minutes without a pulse. The EKG was still showing some irregularity, FDr. leischer said, but no rhythm. Physicians kept Ruby intubated as they waited for the background electrical activity to fade. As they watched the screen in anguish, there was suddenly a blip on the heart rate monitor. Then another and another. Within seconds, Ruby’s heart went back into sinus rhythm.

“We were in disbelief,” Dr. Fleischer said. “We did some tests and put her in the ICU, and she was fine. Usually, after doing compressions on anyone, you’d have bruising or broken ribs. She had nothing. She just woke up and said: ‘What am I doing here? Let me go see my baby.’ ”

Ruby fully recovered, and 3 days later, she went home with her newborn.

While the recovery was unbelievable, Dr. Fleischer stopped short of calling it a medical miracle. There were scientific contributors to her survival: she was immediately intubated when she stopped breathing and compressions were started as soon as her heart stopped.

However, Dr. Fleischer said the fact that lifesaving measures had ended, and Ruby revived on her own was indeed, miraculous.

“It wasn’t like we were doing compressions and brought her back,” he said. “I can scientifically explain things in my mind, except for that. That when we finally stopped and took our hands off her, that’s when something changed. That’s when she came back.”
 

How do ‘medical miracles’ impact physicians?

When Dr. Rotbart was writing his book, which includes physician essays from across the world, he was struck by how many of the events happened decades earlier.

“This is another testament to the powerful impact these experiences have on those witnessing them,” he said. “In many cases, physicians describing events occurring years ago noted that those early memories served to give them hope as they encountered new, seemingly hopeless cases in subsequent years. Some contributors wrote that the ‘miracle experience’ actually directed them in their choice of specialty and has influenced much of their professional decision-making throughout their careers. Others draw on those miraculous moments at times when they themselves feel hopeless in the face of adversity and tragedy.”

Dr. Fleischer said that, although Ruby’s story has stayed with him, his mindset or practice style didn’t necessarily change after the experience.

“I’m not sure if it’s affected me because I haven’t been in that situation again,” he said. “I’m in the middle. I would never rule out anything, but I’m not going to base how I practice on the hope for a medical miracle.”

In a recent opinion piece for the New York Times, pulmonary and critical care physician, Daniela Lamas, MD, wrote about the sometimes negative effects of miracle cases on physicians. Such experiences for instance, can lead to a greater drive to beat the odds in future cases, which can sometimes lead to false hope, protracted critical care admissions, and futile procedures. 

“After all, in most cases in the ICU, our initial prognoses are correct,” she wrote. “So there’s a risk to standing at the bedside, thinking about that one patient who made it home despite our predictions. We can give that experience too much weight in influencing our decisions and recommendations.”

Dr. Beam said unexpected outcomes – particularly in the age of COVID-19 – can certainly make physicians think differently about life-sustaining measures and when to discuss end-of-life care with family members. In his own practice, Dr. Beam has encountered unexpected COVID recoveries. Now, he generally gives extremely ill COVID patients a little more time to see if their bodies recover.

“It remains true that people who are really sick with COVID, who are on ventilated or who are requiring a lot of up respiratory support, they don’t do well on average,” he said. “But it is [also] true that there are a handful of people who get to that point and do come back to 80% or 90% of where they were. It makes you think twice.”
 

What to do when parents hope for a miracle

In his palliative care practice, Nashville, Tenn., surgeon Myrick Shinall Jr., MD, PhD, regularly encounters families and patients who wish for a medical miracle. 

“It happens pretty often from a palliative care perspective,” he said. “What I have experienced the most is a patient with a severe brain injury who we don’t believe is recoverable. The medical team is discussing with the family that it is probably time to discontinue the ventilator. In those situations, families will often talk about wanting us to continue on [our life-sustaining efforts] in the hopes that a miracle will happen.”

Dr. Shinall and Trevor Bibler, PhD, recently authored two articles about best practices for responding to patients who hope for a miracle. The first one, published in the American Journal of Bioethics, is directed toward bioethicists; the second article, in the Journal of Pain and Symptom Management, targets clinicians.

A primary takeaway from the papers is that health professionals should recognize that hope for a miracle may mean different things to different people, said Dr. Bibler, an ethicist and assistant professor at Baylor College of Medicine, Houston. Some patients may have an innocuous hope for a miracle without a religious connotation, whereas others may have a firm conviction in their idea of God, their spirituality, and a concrete vision of the miracle.

“To hear that a family or patient is hoping for a miracle, one shouldn’t assume they already know what the patient or the family might mean by that,” Dr. Bibler said. “If a patient were to say, ‘I hope for a miracle,’ you might ask: ‘What do you mean by a miracle?’ Health professionals should feel empowered to ask that question.”

Health care professionals should explore a patient’s hope for a miracle, be nonjudgmental, ask clarifying questions, restate what the patient has said, and delve into the patient’s world view on death and dying, according to Dr. Bibler’s analyses. In some cases, it may be helpful to include a chaplain or the presence of a theology outsider in discussions. 

When his patients and their families raise the subject of miracles, Dr. Shinall said he inquires what a miracle would look like in their opinion and tries to gauge how much of the assertion is a general hope compared with a firm belief. 

“I try to work with them to make sure they understand doctors’ decisions and recommendations are based on what we know and can predict from our medical experience,” he said. “And that there’s nothing we’re going to do to prevent a miracle from happening, but that that can’t be our medical plan – to wait for a miracle.”

Despite the many patients and families Dr. Shinall has encountered who hope for a miracle, he has never experienced a case that he would describe as a medical miracle, he said. 

Dr. Rotbart believes all physicians struggle with finding balance in how far to push in hope of a miracle and when to let go.

“Miracles, whether they happen to us, or we hear of them from colleagues or we read about them, should humble us as physicians,” he said. “I have come to believe that what we don’t know or don’t understand about medicine, medical miracles, or life in general, isn‘t necessarily cause for fear, and can even be reason for hope.

“Medicine has come a long way since Hippocrates’ theory of The Four Humors and The Four Temperaments, yet we still have much to learn about the workings of the human body. As physicians, we should take comfort in how much we don’t know because that allows us to share hope with our patients and, occasionally, makes medical miracles possible.”

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

Researchers have identified a risk locus on chromosome 7 containing DNA variations that increase the risk that an individual will attempt suicide, even in the absence of a psychiatric disorder.

This finding suggests the genetic underpinnings of suicide attempts are partially shared and partially distinct from those of related psychiatric disorders, the investigators note.

“This study brings us a step closer to understanding the neurobiology of suicidality, with the ultimate goal of developing new treatments and prevention strategies,” Niamh Mullins, PhD, department of psychiatry, department of genetics and genomic sciences, Icahn School of Medicine at Mount Sinai in New York, said in an interview.

The study was published online in Biological Psychiatry.

Largest study to date

In the largest genetic association study of suicide attempt published to date, the researchers conducted a genome-wide association study (GWAS) of 29,782 suicide attempt cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC).

Two loci reached genome-wide significance for suicide attempt – the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with suicide attempt after conditioning on psychiatric disorders and was replicated in an independent cohort of over 14,000 veterans in the Million Veteran Program.

“This is the first replicated genetic locus that contributes more to suicide attempt than related psychiatric disorders,” Dr. Mullins said.

“The study found overlap in the genetic basis of suicide attempt and that of related psychiatric disorders, particularly major depression, but also with that of nonpsychiatric risk factors such as smoking, pain, risk-taking behavior, sleep disturbances, and poorer general health,” Dr. Mullins said.

“These genetic relationships between suicide attempt and nonpsychiatric risk factors were not a by-product of comorbid psychiatric illness, suggesting that there is some shared biological basis between suicide attempt and nonpsychiatric risk factors,” she added.

Dr. Mullins cautioned that the findings do not have any immediate impact on patient care.

“The ultimate goal of this research is to gain insight into the underlying biological pathways involved in suicide attempts or suicidal thoughts, providing potential avenues to treatments and prevention strategies,” she said.

“The study findings also point to the importance of studying the potential direct causal paths between these risk factors and suicide attempt in patients with and without psychiatric illness,” Douglas Ruderfer, PhD, of Vanderbilt University Medical Center, Nashville, Tenn., cofounder and cochair of the consortium and senior author of the paper, added in a news release.

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

Researchers have identified a risk locus on chromosome 7 containing DNA variations that increase the risk that an individual will attempt suicide, even in the absence of a psychiatric disorder.

This finding suggests the genetic underpinnings of suicide attempts are partially shared and partially distinct from those of related psychiatric disorders, the investigators note.

“This study brings us a step closer to understanding the neurobiology of suicidality, with the ultimate goal of developing new treatments and prevention strategies,” Niamh Mullins, PhD, department of psychiatry, department of genetics and genomic sciences, Icahn School of Medicine at Mount Sinai in New York, said in an interview.

The study was published online in Biological Psychiatry.

Largest study to date

In the largest genetic association study of suicide attempt published to date, the researchers conducted a genome-wide association study (GWAS) of 29,782 suicide attempt cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC).

Two loci reached genome-wide significance for suicide attempt – the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with suicide attempt after conditioning on psychiatric disorders and was replicated in an independent cohort of over 14,000 veterans in the Million Veteran Program.

“This is the first replicated genetic locus that contributes more to suicide attempt than related psychiatric disorders,” Dr. Mullins said.

“The study found overlap in the genetic basis of suicide attempt and that of related psychiatric disorders, particularly major depression, but also with that of nonpsychiatric risk factors such as smoking, pain, risk-taking behavior, sleep disturbances, and poorer general health,” Dr. Mullins said.

“These genetic relationships between suicide attempt and nonpsychiatric risk factors were not a by-product of comorbid psychiatric illness, suggesting that there is some shared biological basis between suicide attempt and nonpsychiatric risk factors,” she added.

Dr. Mullins cautioned that the findings do not have any immediate impact on patient care.

“The ultimate goal of this research is to gain insight into the underlying biological pathways involved in suicide attempts or suicidal thoughts, providing potential avenues to treatments and prevention strategies,” she said.

“The study findings also point to the importance of studying the potential direct causal paths between these risk factors and suicide attempt in patients with and without psychiatric illness,” Douglas Ruderfer, PhD, of Vanderbilt University Medical Center, Nashville, Tenn., cofounder and cochair of the consortium and senior author of the paper, added in a news release.

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

Researchers have identified a risk locus on chromosome 7 containing DNA variations that increase the risk that an individual will attempt suicide, even in the absence of a psychiatric disorder.

This finding suggests the genetic underpinnings of suicide attempts are partially shared and partially distinct from those of related psychiatric disorders, the investigators note.

“This study brings us a step closer to understanding the neurobiology of suicidality, with the ultimate goal of developing new treatments and prevention strategies,” Niamh Mullins, PhD, department of psychiatry, department of genetics and genomic sciences, Icahn School of Medicine at Mount Sinai in New York, said in an interview.

The study was published online in Biological Psychiatry.

Largest study to date

In the largest genetic association study of suicide attempt published to date, the researchers conducted a genome-wide association study (GWAS) of 29,782 suicide attempt cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC).

Two loci reached genome-wide significance for suicide attempt – the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with suicide attempt after conditioning on psychiatric disorders and was replicated in an independent cohort of over 14,000 veterans in the Million Veteran Program.

“This is the first replicated genetic locus that contributes more to suicide attempt than related psychiatric disorders,” Dr. Mullins said.

“The study found overlap in the genetic basis of suicide attempt and that of related psychiatric disorders, particularly major depression, but also with that of nonpsychiatric risk factors such as smoking, pain, risk-taking behavior, sleep disturbances, and poorer general health,” Dr. Mullins said.

“These genetic relationships between suicide attempt and nonpsychiatric risk factors were not a by-product of comorbid psychiatric illness, suggesting that there is some shared biological basis between suicide attempt and nonpsychiatric risk factors,” she added.

Dr. Mullins cautioned that the findings do not have any immediate impact on patient care.

“The ultimate goal of this research is to gain insight into the underlying biological pathways involved in suicide attempts or suicidal thoughts, providing potential avenues to treatments and prevention strategies,” she said.

“The study findings also point to the importance of studying the potential direct causal paths between these risk factors and suicide attempt in patients with and without psychiatric illness,” Douglas Ruderfer, PhD, of Vanderbilt University Medical Center, Nashville, Tenn., cofounder and cochair of the consortium and senior author of the paper, added in a news release.

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