Mixed Topics

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?

Continue to the answer...

Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)

What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?

Continue to the answer...

Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)

What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?

Continue to the answer...

Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

Peter Schwartz, MD, was chair of the department of obstetrics and gynecology at a hospital in Reading, Pa., in the mid-1990s when a young physician sought him out. The doctor, whom Dr. Schwartz regarded as talented and empathetic, was visibly shaken. The expectant mother they were caring for had just lost her unborn child.

“The doctor came into my office within an hour of the event and asked me to look at the case,” Dr. Schwartz recalled. “I could see that they had failed to recognize ominous changes in the fetal heart rate, and I faced the pain of having to tell them, ‘I think this could have been handled much better.’” Dr. Schwartz delivered the news as compassionately as he could, but a subsequent review confirmed his suspicion: The doctor had made a serious error.

“The doctor was devastated,” he said. “She got counseling and took time off, but in the end, she quit practicing medicine. She said, ‘If I keep practicing, something like that could happen again, and I don’t think I could handle it.’”

To err may be human, but in a health care setting, the harm can be catastrophic. While patients and their families are the ones who suffer most, doctors can be so traumatized by their medical mistakes that their feelings of guilt, shame, and self-doubt can lead to depression, anxiety, post-traumatic stress disorder, and even suicidal ideation. The trauma can be so profound that, in a now famous 2000 editorial in the British Medical Journal, Albert Wu, MD, gave the phenomenon a name: “second victim syndrome.”

Today, as quality improvement organizations and health systems work to address medical errors in a just and transparent way, they’re realizing that finding ways to help traumatized clinicians is integral to their efforts.
 

Are doctors really ‘second victims?’

Although the medical field is moving away from the term “second victim,” which patient advocates argue lacks a ring of accountability, the emotional trauma doctors and other clinicians endure is garnering increased attention. In the 2 decades since Dr. Wu wrote his editorial, research has shown that many types of adverse health care events can evoke traumatic responses. In fact, studies indicate that from 10.4% to 43.3% of health care workers may experience negative symptoms following an adverse event.

But for doctors – who have sworn an oath to do no harm – the emotional toll of having committed a serious medical error can be particularly burdensome and lingering. In a Dutch study involving more than 4,300 doctors and nurses, respondents who were involved in a patient safety incident that resulted in harm were nine times more likely to have negative symptoms lasting longer than 6 months than those who were involved in a near-miss experience.

“There’s a feeling of wanting to erase yourself,” says Danielle Ofri, MD, a New York internist and author of “When We Do Harm: A Doctor Confronts Medical Error.”

That emotional response can have a profound impact on the way medical errors are disclosed, investigated, and ultimately resolved, said Thomas Gallagher, MD, an internist and executive director of the Collaborative for Accountability and Improvement, a patient safety program at the University of Washington.

“When something goes wrong, as physicians, we don’t know what to do,” Dr. Gallagher says. “We feel awful, and often our human reflexes lead us astray. The doctor’s own emotions become barriers to addressing the situation.” For example, guilt and shame may lead doctors to try to hide or diminish their mistakes. Some doctors might try to shift blame, while others may feel so guilty they assume they were responsible for an outcome that was beyond their control.

Recognizing that clinicians’ responses to medical errors are inextricably tangled with how those events are addressed, a growing number of health systems are making clinician support a key element when dealing with medical errors.
 

Emotional first aid

Although it’s typical for physicians to feel isolated in the wake of errors, these experiences are far from unique. Research conducted by University of Missouri Health Care nurse scientist Susan Scott, RN, PhD, shows that just as most individuals experiencing grief pass through several distinct emotional stages, health care professionals who make errors go through emotional stages that may occur sequentially or concurrently.

An initial period of chaos is often followed by intrusive reflections, haunting re-enactments, and feelings of inadequacy. The doctor’s thinking moves from “How did that happen?” to “What did I miss?” to “What will people think about me?” As the error comes under scrutiny by quality improvement organizations, licensing boards, and/or lawyers, the doctor feels besieged. The doctor may want to reach out but is afraid to. According to Dr. Scott, only 15% of care providers ask for help.

Recognizing that physicians and other care providers rarely ask for support – or may not realize they need it – a growing number of health systems are implementing Communication and Resolution Programs (CRPs). Rather than respond to medical errors with a deny-and-defend mentality, CRPs emphasize transparency and accountability.

This approach, which the Agency for Healthcare Research and Quality has embraced and codified with its Communication and Optimal Resolution (CANDOR) toolkit, focuses on prompt incident reporting; communication with and support for patients, family members, and caregivers affected by the event; event analysis; quality improvement; and just resolution of the event, including apologies and financial compensation where appropriate.

The CANDOR toolkit, which includes a module entitled Care for the Caregiver, directs health systems to identify individuals and establish teams, led by representatives from patient safety and/or risk management, who can respond promptly to an event. After ensuring the patient is clinically stable and safe, the CANDOR process provides for immediate and ongoing emotional support to the patient, the family, and the caregiver.

“A lot of what CRPs are about is creating structures and processes that normalize an open and compassionate response to harm events in medicine,” says Dr. Gallagher, who estimates that between 400 and 500 health systems now have CRPs in place.
 

Wisdom through adversity

While clinicians experience many difficult and negative emotions in the wake of medical errors, how they move forward after the event varies markedly. Some, unable to come to terms with the trauma, may move to another institution or leave medicine entirely. Others, while occasionally reliving the trauma, learn to cope. For the most fortunate, enduring the trauma of a medical error can lead to growth, insight, and wisdom.

In an article published in the journal Academic Medicine, researchers asked 61 physicians who had made serious medical errors, “What helped you to cope positively?” Some of the most common responses – talking about their feelings with a peer, disclosing and apologizing for a mistake, and developing system changes to prevent additional errors – are baked into some health systems’ CRP programs. Other respondents said they dedicated themselves to learning from the mistake, becoming experts in a given field, or sharing what they learned from the experience through teaching.

Dr. Ofri said that after she made an error decades ago while managing a patient with diabetic ketoacidosis, her senior resident publicly berated her for it. The incident taught her a clinical lesson: Never remove an insulin drip without administering long-acting insulin. More importantly, the resident’s verbal thumping taught her about the corrosive effects of shame. Today, Dr. Ofri, who works in a teaching hospital, says that when meeting a new medical team, she begins by recounting her five biggest medical errors.

“I want them to come to me if they make a mistake,” she says. “I want to first make sure the patient is okay. But then I want to make sure the doctor is okay. I also want to know: What was it about the system that contributed to the error, and what can we do to prevent similar errors in the future?”
 

Acceptance and compassion

Time, experience, supportive peers, an understanding partner or spouse: all of these can help a doctor recover from the trauma of a mistake. “But they’re not an eraser,” Dr. Schwartz said.

Sometimes, doctors say, the path forward starts with acceptance.

Jan Bonhoeffer, MD, author of “Dare to Care: How to Survive and Thrive in Today’s Medical World,” tells a story about a mistake that transformed his life. In 2004, he was working in a busy London emergency department when an adolescent girl arrived complaining of breathing trouble. Dr. Bonhoeffer diagnosed her with asthma and discharged her with an inhaler. The next day, the girl was back in the hospital – this time in the ICU, intubated, and on a ventilator. Because he had failed to take an x-ray, Dr. Bonhoeffer missed the tumor growing in the girl’s chest.

Dr. Bonhoeffer was shattered by his error. “After that experience, I knew I wanted to make learning from my mistakes part of my daily practice,” he says. Now, at the end of each workday, Dr. Bonhoeffer takes an inventory of the day and reflects on all his actions, large and small, clinical and not. “I take a few minutes and think about everything I did and what I should have done differently,” he said. The daily practice can be humbling because it forces him to confront his errors, but it is also empowering, he said, “because the next day I get to make a different choice.”

Dr. Bonhoeffer added, “Doctors are fallible, and you have to be compassionate with yourself. Compassion isn’t sweet. It’s not motherhood and honey pies. It’s coming to terms with reality. It’s not a cure, but it’s healing.”

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

The recommended vaccination schedule for people in the United States aged 19 years and older has been released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC).

The Clinical Guideline on the “Recommended Adult Immunization Schedule, United States, 2022” appears online Feb. 17 in Annals of Internal Medicine and in the CDC’s Morbidity and Mortality Weekly Report.

The document features changes to the zoster, pneumococcal, and hepatitis B vaccines. COVID-19 vaccinations are now included in the notes section of the schedule and can be co-administered with other vaccines, according to ACIP.

The 2022 schedule is particularly important because the pandemic has caused many adults to fall behind in routine vaccinations, according to lead author Neil Murthy, MD, MPH, MSJ, of the CDC’s immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.  

“Providers should administer all due and overdue vaccines according to the routine immunization schedule during the same visit,” the group wrote. “In addition, providers should implement strategies to catch up all patients on any overdue vaccines.”

Among other changes appearing in the 2022 recommendations:

• A new step 4 in the form of an appendix lists all the contraindications and precautions for each vaccine.
• The zoster vaccine now is recommended for use in everyone aged 19 years and older who are or will be immunodeficient or immunosuppressed through disease or therapy. The new purple color bar reflects ACIP’s new two-dose series regimen for immunocompromised adults aged 19 to 49.
• The simplified pneumococcal recommendation includes guidance on using the new PCV15 and PCV20 vaccines.
• The hepatitis B recommendation has been made more inclusive, with vaccination recommended for all adults aged 19 to 59. The Special Situations section in the Notes outlines the risk-based recommendations for the hepatitis B vaccine in adults aged 60 and older. The schedule has been harmonized with the 2022 Child and Adolescent Immunization Schedule.

A welcome change

Sandra A. Fryhofer, MD, a member of the ACIP Combined Immunization Work Group, said the new pneumococcal recommendation is a particularly welcome change.

“The old recommendation was complicated and confusing. The new one is much more straightforward,” Dr. Fryhofer, an internist in Atlanta, said in an interview. Now there are only two options: a two-vaccine series of PCV15 (Vaxneuvance), in combination with the already familiar PPSV23 polysaccharide vaccine (Pneumovax 23), and a single dose of the new PCV20, Prevnar 20.

“Some work group members favored a universal age-based recommendation starting at 50 instead of 65,” Fryhofer said. “This would provide more opportunities to vaccinate adults but could lead to waning immunity later in life when risk of disease is higher.”

Although none of the updates is likely to stir controversy, discussion among ACIP members was particularly lively around hepatitis B vaccination, Dr. Fryhofer said. This vaccine has historically been recommended based on risk and has had poor uptake, while age-based vaccine recommendations generally have greater uptake.

“ACIP approved hepatitis B vaccine universally for those up to age 60, but for those 60 and older, the recommendation remains risk-based with a loophole: Anyone 60 and older who wants it can get it,” she told this news organization. “Some of the risk indications for hepatitis B vaccination may be uncomfortable or embarrassing to disclose, especially for older patients. The loophole takes care of that, but patients may have to ask for the vaccine.”

As usual, the graphics have been fine-tuned for greater accuracy and readability. “You can print a color copy to have in the exam room or at your workspace or give it a bookmark and check it online,” Dr. Fryhofer said. “It’s a great resource to have at your fingertips.”

Dr. Fryhofer has made a series of videos explaining ACIP’s approval process, the use of the schedule, and changes to vaccines including influenza. These can be accessed on the American College of Physicians website.

The authors of the recommendations stress that physicians should pay careful attention to the notes section for each vaccine, as these details clarify who needs what vaccine, when, and at what dose.

Co-author Henry Bernstein, DO, reported that he is the editor of Current Opinion in Pediatrics Office Pediatrics Series and received a presentation honorarium from the Florida chapter of the American Academy of Pediatrics. Co-author Kevin Ault, MD, reported having received a grant from the National Cancer Institute, consulting fees from PathoVax, and payments supporting attending meetings and/or travel from the American College of Obstetricians and Gynecologists.

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

While the representation of women in radiation oncology and medical oncology academic faculties has increased over time, racial and ethnic minorities are still vastly underrepresented in these fields, according to a cross-sectional study of data from the Association of American Medical Colleges.

“Creating and maintaining a diverse health care workforce is a priority to help combat societal inequities and health disparities, particularly in light of the evolving demographic characteristics of the general U.S. population,” wrote authors who were led by Sophia C. Kamran, MD, a radiation oncologist with Massachusetts General Hospital, Boston.

The study, which was published Dec. 9 in JAMA Oncology, surveyed full-time U.S.-based faculty in radiation and medical oncology departments from 1970 through 2019.

Improved patient satisfaction, compliance, and outcomes have been documented when a health care workforce better reflects the demographic traits of those whom it serves, Dr. Kamran and associates wrote.

They point to recent increases in the number and urgency of calls for improved diversity in the health care workforce, citing also higher incidence and mortality of new cancer cases among Black, indigenous, and Hispanic populations, compared with their non-Hispanic White counterparts. Prior calls for health care work force diversity have led to some creation of opportunities and pathways for increased representation of women and racial and ethnic minority groups in medicine, and the overall diversity of medical school faculty has been increasing by race and ethnicity and sex.

The change, however, is of lesser magnitude than what has been seen among medical school applicants, students, and graduates, and the gains in medical school faculty diversity have not kept pace with increasing diversity of the U.S. population. It has remained unclear whether corresponding progress has occurred in the composition of radiation oncology and medical oncology departments during the last 5 decades.
 

Despite lack of diversity, total faculty numbers have increased

Dr. Kamran and associates’ analysis revealed that total faculty numbers increased over time in both radiation oncology and medical oncology, with faculty representation of underrepresented-in-medicine (URM) women proportionally increased by 0.1% per decade in both radiation oncology (95% confidence interval, 0.005%-0.110%; P < . 001 for trend) and medical oncology (95% CI, −0.03% to 0.16%; P = .06 for trend), compared with non–URM women faculty, which increased by 0.4% (95% CI, 0.25%-0.80%) per decade in radiation oncology and 0.7% (95% CI, 0.47%-0.87%) per decade in medical oncology (P < .001 for trend for both). Faculty representation of URM men did not significantly change for radiation oncology (0.03% per decade [95% CI, −0.008% to 0.065%]; P = .09 for trend) or for medical oncology (0.003% per decade [95% CI, −0.13% to 0.14%]; P = .94 for trend).

In both 2009 and 2019, representation of both women and URM individuals for both specialties was less than their representation in the U.S. population. Radiation oncology faculty had the lowest URM representation in 2019 at 5.1%. The number of total URM faculty represented among both medical oncology and radiation oncology remained low for every rank in 2019 (Medical oncology: instructor, 2 of 44 [5%]; assistant professor, 18 of 274 [7%]; associate professor, 13 of 177 [7%]; full professor, 13 of 276 [5%]. Radiation oncology: instructor, 9 of 147 [6%]; assistant professor, 57 of 927 [6%]; associate professor, 20 of 510 [4%]; full professor, 18 of 452 [4%]).

“Our results highlight significant diversity differences along the career ladder in both specialties, with women having lower academic rank than men throughout the study period, and underrepresented [racial and ethnic groups] at every rank,” the authors wrote.

And, although Black, Hispanic, and indigenous people make up about 31% of the U.S. population, their inclusion in the health care workforce trails at all stages in the pipeline, the investigators found.

Diversity among radiation and medical oncologists lags behind that of medical school diversity in general, which has grown through efforts by the Association of American Medical Colleges.

Despite some improvements, the authors suggest the need for more initiatives to retain racial and ethnic minorities in an effort to reflect the diversity of the U.S. cancer population.

“This is a multifactorial issue, with focus not only on increasing diversity of the upstream pipeline but maintaining diversity throughout the entire pipeline, requiring difficult but necessary conversations about racial and ethnic systemic bias, lack of exposure and opportunities, and financial toxicities and pressures, to name a few. Until these factors are further delineated and better addressed, focused and targeted mentorship is key,” the authors wrote.
 

Small steps can have a collective impact

In a commentary published with the study, Frederick Lansigan, MD, and Charles R. Thomas Jr, MD, both of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., called for a systemic change in hiring practices.

“Any small steps of change that contribute to supporting the issues highlighted by the Kamran et al. study can have a collective positive impact. A holistic evaluation of [underrepresented] applicants at all stages of education and training is paramount, and joining selection committees is necessary to ensure fair processes. Mentoring programs, leadership courses, and addressing microaggressions and mistreatment may improve retention of [underrepresented] medical school matriculants and trainees in oncology. Cancer centers can build and lead visible and tangible diversity, equity, inclusion, justice, and belonging efforts as we are doing at our institution,” the physicians wrote.

But above all, Dr. Lansigan and Dr. Thomas said that the oncology community needs to agree that intentionally increasing the number of underrepresented physicians in the U.S. workforce is necessary to better address health care inequities.

“We need all hands on deck to reduce structural barriers in early education. We need STEM programs that start in elementary school and offer support through college. Oncologists can mentor these early learners to highlight the positive aspects of a career in oncology, the importance of [underrepresented] physicians in oncology, and the resilience required in caring for those with serious illness, many of whom will come from underserved populations. “Physicians and public health experts themselves who are interested in tackling the discrepancy between [underrepresented] and [non-underrepresented] medical school [students] and oncology trainees need to seek and be elected into positions that can start to balance this equation. If more are willing to acknowledge the structural inequities that exist in the oncology workforce pipeline, we can start to solve the complex equation of structural inequities.”

Dr Lansigan reported being the Interim Associate Dean of Diversity, Equity, and Inclusion at the Geisel School of Medicine and the Principal of Diversity, Equity, and Inclusion for the department of medicine at Dartmouth-Hitchcock Medical Center. No other disclosures were reported.

While the representation of women in radiation oncology and medical oncology academic faculties has increased over time, racial and ethnic minorities are still vastly underrepresented in these fields, according to a cross-sectional study of data from the Association of American Medical Colleges.

“Creating and maintaining a diverse health care workforce is a priority to help combat societal inequities and health disparities, particularly in light of the evolving demographic characteristics of the general U.S. population,” wrote authors who were led by Sophia C. Kamran, MD, a radiation oncologist with Massachusetts General Hospital, Boston.

The study, which was published Dec. 9 in JAMA Oncology, surveyed full-time U.S.-based faculty in radiation and medical oncology departments from 1970 through 2019.

Improved patient satisfaction, compliance, and outcomes have been documented when a health care workforce better reflects the demographic traits of those whom it serves, Dr. Kamran and associates wrote.

They point to recent increases in the number and urgency of calls for improved diversity in the health care workforce, citing also higher incidence and mortality of new cancer cases among Black, indigenous, and Hispanic populations, compared with their non-Hispanic White counterparts. Prior calls for health care work force diversity have led to some creation of opportunities and pathways for increased representation of women and racial and ethnic minority groups in medicine, and the overall diversity of medical school faculty has been increasing by race and ethnicity and sex.

The change, however, is of lesser magnitude than what has been seen among medical school applicants, students, and graduates, and the gains in medical school faculty diversity have not kept pace with increasing diversity of the U.S. population. It has remained unclear whether corresponding progress has occurred in the composition of radiation oncology and medical oncology departments during the last 5 decades.
 

Despite lack of diversity, total faculty numbers have increased

Dr. Kamran and associates’ analysis revealed that total faculty numbers increased over time in both radiation oncology and medical oncology, with faculty representation of underrepresented-in-medicine (URM) women proportionally increased by 0.1% per decade in both radiation oncology (95% confidence interval, 0.005%-0.110%; P < . 001 for trend) and medical oncology (95% CI, −0.03% to 0.16%; P = .06 for trend), compared with non–URM women faculty, which increased by 0.4% (95% CI, 0.25%-0.80%) per decade in radiation oncology and 0.7% (95% CI, 0.47%-0.87%) per decade in medical oncology (P < .001 for trend for both). Faculty representation of URM men did not significantly change for radiation oncology (0.03% per decade [95% CI, −0.008% to 0.065%]; P = .09 for trend) or for medical oncology (0.003% per decade [95% CI, −0.13% to 0.14%]; P = .94 for trend).

In both 2009 and 2019, representation of both women and URM individuals for both specialties was less than their representation in the U.S. population. Radiation oncology faculty had the lowest URM representation in 2019 at 5.1%. The number of total URM faculty represented among both medical oncology and radiation oncology remained low for every rank in 2019 (Medical oncology: instructor, 2 of 44 [5%]; assistant professor, 18 of 274 [7%]; associate professor, 13 of 177 [7%]; full professor, 13 of 276 [5%]. Radiation oncology: instructor, 9 of 147 [6%]; assistant professor, 57 of 927 [6%]; associate professor, 20 of 510 [4%]; full professor, 18 of 452 [4%]).

“Our results highlight significant diversity differences along the career ladder in both specialties, with women having lower academic rank than men throughout the study period, and underrepresented [racial and ethnic groups] at every rank,” the authors wrote.

And, although Black, Hispanic, and indigenous people make up about 31% of the U.S. population, their inclusion in the health care workforce trails at all stages in the pipeline, the investigators found.

Diversity among radiation and medical oncologists lags behind that of medical school diversity in general, which has grown through efforts by the Association of American Medical Colleges.

Despite some improvements, the authors suggest the need for more initiatives to retain racial and ethnic minorities in an effort to reflect the diversity of the U.S. cancer population.

“This is a multifactorial issue, with focus not only on increasing diversity of the upstream pipeline but maintaining diversity throughout the entire pipeline, requiring difficult but necessary conversations about racial and ethnic systemic bias, lack of exposure and opportunities, and financial toxicities and pressures, to name a few. Until these factors are further delineated and better addressed, focused and targeted mentorship is key,” the authors wrote.
 

Small steps can have a collective impact

In a commentary published with the study, Frederick Lansigan, MD, and Charles R. Thomas Jr, MD, both of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., called for a systemic change in hiring practices.

“Any small steps of change that contribute to supporting the issues highlighted by the Kamran et al. study can have a collective positive impact. A holistic evaluation of [underrepresented] applicants at all stages of education and training is paramount, and joining selection committees is necessary to ensure fair processes. Mentoring programs, leadership courses, and addressing microaggressions and mistreatment may improve retention of [underrepresented] medical school matriculants and trainees in oncology. Cancer centers can build and lead visible and tangible diversity, equity, inclusion, justice, and belonging efforts as we are doing at our institution,” the physicians wrote.

But above all, Dr. Lansigan and Dr. Thomas said that the oncology community needs to agree that intentionally increasing the number of underrepresented physicians in the U.S. workforce is necessary to better address health care inequities.

“We need all hands on deck to reduce structural barriers in early education. We need STEM programs that start in elementary school and offer support through college. Oncologists can mentor these early learners to highlight the positive aspects of a career in oncology, the importance of [underrepresented] physicians in oncology, and the resilience required in caring for those with serious illness, many of whom will come from underserved populations. “Physicians and public health experts themselves who are interested in tackling the discrepancy between [underrepresented] and [non-underrepresented] medical school [students] and oncology trainees need to seek and be elected into positions that can start to balance this equation. If more are willing to acknowledge the structural inequities that exist in the oncology workforce pipeline, we can start to solve the complex equation of structural inequities.”

Dr Lansigan reported being the Interim Associate Dean of Diversity, Equity, and Inclusion at the Geisel School of Medicine and the Principal of Diversity, Equity, and Inclusion for the department of medicine at Dartmouth-Hitchcock Medical Center. No other disclosures were reported.

While the representation of women in radiation oncology and medical oncology academic faculties has increased over time, racial and ethnic minorities are still vastly underrepresented in these fields, according to a cross-sectional study of data from the Association of American Medical Colleges.

“Creating and maintaining a diverse health care workforce is a priority to help combat societal inequities and health disparities, particularly in light of the evolving demographic characteristics of the general U.S. population,” wrote authors who were led by Sophia C. Kamran, MD, a radiation oncologist with Massachusetts General Hospital, Boston.

The study, which was published Dec. 9 in JAMA Oncology, surveyed full-time U.S.-based faculty in radiation and medical oncology departments from 1970 through 2019.

Improved patient satisfaction, compliance, and outcomes have been documented when a health care workforce better reflects the demographic traits of those whom it serves, Dr. Kamran and associates wrote.

They point to recent increases in the number and urgency of calls for improved diversity in the health care workforce, citing also higher incidence and mortality of new cancer cases among Black, indigenous, and Hispanic populations, compared with their non-Hispanic White counterparts. Prior calls for health care work force diversity have led to some creation of opportunities and pathways for increased representation of women and racial and ethnic minority groups in medicine, and the overall diversity of medical school faculty has been increasing by race and ethnicity and sex.

The change, however, is of lesser magnitude than what has been seen among medical school applicants, students, and graduates, and the gains in medical school faculty diversity have not kept pace with increasing diversity of the U.S. population. It has remained unclear whether corresponding progress has occurred in the composition of radiation oncology and medical oncology departments during the last 5 decades.
 

Despite lack of diversity, total faculty numbers have increased

Dr. Kamran and associates’ analysis revealed that total faculty numbers increased over time in both radiation oncology and medical oncology, with faculty representation of underrepresented-in-medicine (URM) women proportionally increased by 0.1% per decade in both radiation oncology (95% confidence interval, 0.005%-0.110%; P < . 001 for trend) and medical oncology (95% CI, −0.03% to 0.16%; P = .06 for trend), compared with non–URM women faculty, which increased by 0.4% (95% CI, 0.25%-0.80%) per decade in radiation oncology and 0.7% (95% CI, 0.47%-0.87%) per decade in medical oncology (P < .001 for trend for both). Faculty representation of URM men did not significantly change for radiation oncology (0.03% per decade [95% CI, −0.008% to 0.065%]; P = .09 for trend) or for medical oncology (0.003% per decade [95% CI, −0.13% to 0.14%]; P = .94 for trend).

In both 2009 and 2019, representation of both women and URM individuals for both specialties was less than their representation in the U.S. population. Radiation oncology faculty had the lowest URM representation in 2019 at 5.1%. The number of total URM faculty represented among both medical oncology and radiation oncology remained low for every rank in 2019 (Medical oncology: instructor, 2 of 44 [5%]; assistant professor, 18 of 274 [7%]; associate professor, 13 of 177 [7%]; full professor, 13 of 276 [5%]. Radiation oncology: instructor, 9 of 147 [6%]; assistant professor, 57 of 927 [6%]; associate professor, 20 of 510 [4%]; full professor, 18 of 452 [4%]).

“Our results highlight significant diversity differences along the career ladder in both specialties, with women having lower academic rank than men throughout the study period, and underrepresented [racial and ethnic groups] at every rank,” the authors wrote.

And, although Black, Hispanic, and indigenous people make up about 31% of the U.S. population, their inclusion in the health care workforce trails at all stages in the pipeline, the investigators found.

Diversity among radiation and medical oncologists lags behind that of medical school diversity in general, which has grown through efforts by the Association of American Medical Colleges.

Despite some improvements, the authors suggest the need for more initiatives to retain racial and ethnic minorities in an effort to reflect the diversity of the U.S. cancer population.

“This is a multifactorial issue, with focus not only on increasing diversity of the upstream pipeline but maintaining diversity throughout the entire pipeline, requiring difficult but necessary conversations about racial and ethnic systemic bias, lack of exposure and opportunities, and financial toxicities and pressures, to name a few. Until these factors are further delineated and better addressed, focused and targeted mentorship is key,” the authors wrote.
 

Small steps can have a collective impact

In a commentary published with the study, Frederick Lansigan, MD, and Charles R. Thomas Jr, MD, both of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., called for a systemic change in hiring practices.

“Any small steps of change that contribute to supporting the issues highlighted by the Kamran et al. study can have a collective positive impact. A holistic evaluation of [underrepresented] applicants at all stages of education and training is paramount, and joining selection committees is necessary to ensure fair processes. Mentoring programs, leadership courses, and addressing microaggressions and mistreatment may improve retention of [underrepresented] medical school matriculants and trainees in oncology. Cancer centers can build and lead visible and tangible diversity, equity, inclusion, justice, and belonging efforts as we are doing at our institution,” the physicians wrote.

But above all, Dr. Lansigan and Dr. Thomas said that the oncology community needs to agree that intentionally increasing the number of underrepresented physicians in the U.S. workforce is necessary to better address health care inequities.

“We need all hands on deck to reduce structural barriers in early education. We need STEM programs that start in elementary school and offer support through college. Oncologists can mentor these early learners to highlight the positive aspects of a career in oncology, the importance of [underrepresented] physicians in oncology, and the resilience required in caring for those with serious illness, many of whom will come from underserved populations. “Physicians and public health experts themselves who are interested in tackling the discrepancy between [underrepresented] and [non-underrepresented] medical school [students] and oncology trainees need to seek and be elected into positions that can start to balance this equation. If more are willing to acknowledge the structural inequities that exist in the oncology workforce pipeline, we can start to solve the complex equation of structural inequities.”

Dr Lansigan reported being the Interim Associate Dean of Diversity, Equity, and Inclusion at the Geisel School of Medicine and the Principal of Diversity, Equity, and Inclusion for the department of medicine at Dartmouth-Hitchcock Medical Center. No other disclosures were reported.

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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

On Feb. 15, Robert Califf, MD, narrowly won Senate confirmation to once again serve as the commissioner of the Food and Drug Administration, overcoming protest votes from lawmakers about abortion and opioid issues.

FDA photo by Michael J. Ermarth

The Senate voted 50-46 in favor of Dr. Califf’s nomination. A cardiologist long affiliated with Duke University and a noted expert on clinical trials, Dr. Califf also led the FDA from February 2016 through January 2017.

In 2016, the Senate confirmed him as FDA chief in an 89-4 vote. At that time, Sen. Joe Manchin, D-WV, and a few other senators said they were concerned that Dr. Califf’s links to the drug industry would hamper his ability to regulate drugmakers, particularly in terms of rules on prescription painkillers.

Sen. Manchin also objected to Dr. Califf’s second nomination as FDA commissioner, as did several fellow Democrats, including Sen. Edward Markey of Massachusetts. In a statement issued after the Feb. 15 vote, Sen. Markey said he has “consistently raised concerns about the FDA’s egregious mishandling of opioid approvals and its role in enabling the current opioid epidemic.”

“To date, the FDA still has not implemented many of the reforms necessary to ensure that it is fulfilling its role as our nation’s top pharmaceutical cop on the beat,” Sen. Markey said. “I have not received any real commitment from Dr. Califf to truly reform the FDA or to learn from the failures that fueled this public health crisis.”

This time, Dr. Califf lost support among Republican senators due to objections raised by groups seeking to end women’s access to abortion. Susan B. Anthony List and National Right to Life asked senators in a January letter to oppose Dr. Califf’s nomination, citing their objections to how the FDA handled reporting of adverse events from abortions by medication during Dr. Califf’s Tenure.

But some Republicans supported Califf in the Tuesday vote. Sens. Roy Blunt of Missouri, Richard Burr of North Carolina, Susan Collins of Maine, Lisa Murkowski of Alaska, Mitt Romney of Utah, and Pat Toomey of Pennsylvania all voted in his favor.

On Feb. 14, Sen. Patty Murray, D-WA, chairwoman of the Senate Health, Education, Labor, and Pensions Committee, urged her colleagues to vote for Dr. Califf to give the FDA strong leadership to tackle urgent health needs such as the opioid crisis, youth tobacco use, antimicrobial resistance, and inequities in health care.

“At this critical moment, we need a trusted hand to lead the FDA,” she said in a floor speech. Dr. Califf’s previous service at the FDA and his years spent as a research scientist “give him the experience to take on this challenge.”

Separately, three former FDA commissioners on Feb. 15 published an opinion article that appeared in The Hill. Republican presidents nominated two of these former FDA chiefs: Scott Gottlieb, MD, and Mark McClellan, MD. The third, Margaret Hamburg, MD, was nominated by President Barack Obama, as was Dr. Califf for his first time as FDA chief.

There’s an urgent need for a confirmed leader at the FDA as the United States seeks to move beyond the pandemic, the former FDA chiefs wrote. The work ahead includes continued efforts with vaccines as well as efforts to bolster medical supply chains, they said.

Dr. Califf “knows how to advance the safe development and use of medical products and to bring a sound, science-based foundation to the FDA’s regulatory actions. Because of this, he has earned the confidence of FDA’s professional career staff, as well as a broad base of patient groups, academic experts, medical professionals, and public health organizations,” Dr. Gottlieb, Dr. Hamburg, and Dr. McClellan wrote.

The article also was signed by former Centers for Medicare and Medicaid Services Administrator Andy Slavitt, who served in the Obama administration.
 

Support of medical community

The American Heart Association issued a statement on Feb.15, congratulating Dr. Califf on his second confirmation after the Senate vote.

“With a distinguished career in public service and a long-time volunteer leader at the American Heart Association, Dr. Califf has honed his ability to communicate and build trust with diverse constituencies,” CEO Nancy Brown said in the statement. “He will use his experience as a cardiologist to safeguard the health and well-being of people throughout the country, and his background in research to prioritize science and evidence-based policymaking.”

Dr. Califf was also backed by the Association of American Medical Colleges, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians when he was nominated for the role last year by President Joe Biden.

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

The vitamin D story exudes teaching points: It offers a master class in critical appraisal, connecting the concepts of biologic plausibility, flawed surrogate markers, confounded observational studies, and slews of randomized controlled trials (RCTs) showing no benefits on health outcomes.

Yet despite the utter lack of benefit seen in trials, the hype continues. And the pandemic has only enhanced this hype as an onslaught of papers have reported the association of low vitamin D levels and COVID-19 disease.

My questions are simple: Why doesn’t the evidence persuade people? How many nonsignificant trials do we need before researchers stop studying vitamin D, doctors stop (routinely) measuring levels, and patients stop wasting money on the unhelpful supplement? What are the implications for this lack of persuasion?

Before exploring these questions, I want to set out that symptomatic vitamin deficiencies of any sort ought to be corrected. 
 

Biologic plausibility and the pull of observational studies

It has long been known that vitamin D is crucial for bone health and that it can be produced in the skin with sun exposure. In the last decade, however, experts note that nearly every tissue and cell in our body has a vitamin D receptor. It then follows that if this many cells in the body can activate vitamin D, it must be vital for cardiovascular health, immune function, cancer prevention: basically, everything health related.

Oodles of observational studies have found that low serum levels of vitamin D correlate with higher mortality from all causes, cancer, cardiovascular disease, and now even COVID-19. Yet no matter the amount of statistical adjustment in these studies, we cannot know whether these associations are due to true causality.

The major issue is confounding: That is, people with low vitamin D levels have other conditions or diseases that lead to higher rates of ill health. Consider a patient with obesity, arthritis, and cognitive decline; this person is unlikely to do much exercise in the sun and may have low vitamin D levels. The low vitamin D level is simply a marker of overall poor health.
 

The randomized controlled trials tell a clear story

There are hundreds of vitamin D RCTs. The results simplify into one sentence: Vitamin D supplements do not improve health outcomes.

Here is a short summary of some recent studies.

VITAL, a massive (N > 25,000) RCT with 5 years of follow-up, compared vitamin D supplements to placebo and found no differences in the primary endpoints of cancer or cardiac events. Rates of death from any cause were nearly identical. Crucially, in subgroup analyses, the effects did not vary according to vitamin D levels at baseline.

The D-Health investigators randomly assigned more than 21,000 adults to vitamin D or placebo and after 5.7 years of follow-up reported no differences in the primary endpoint of overall mortality. There also were no differences in cardiovascular disease mortality.

Then you have the Mendelian randomized studies, which some have called nature’s RCT. These studies take advantage of the fact that some people are born with gene variations that predispose to low vitamin D levels. More than 60 Mendelian randomization studies have evaluated the consequences of lifelong genetically lowered vitamin D levels on various outcomes; most of these have found null effects.

Then there are the meta-analyses and systematic reviews. I loved the conclusion of this review of systematic reviews from the BMJ (emphasis mine):

“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.”

 

The failure to persuade

My original plan was to emphasize the power of the RCT. Despite strong associations of low vitamin D levels with poor outcomes, the trials show no benefit to treatment. This strongly suggests (or nearly proves) that low vitamin D levels are akin to premature ventricular complexes after myocardial infarction: a marker for risk but not a target for therapy.

But I now see the more important issue as why scientists, funders, clinicians, and patients are not persuaded by clear evidence. Every day in clinic I see patients on vitamin D supplements; the journals keep publishing vitamin D studies. The proponents of vitamin D remain positive. And lately there is outsized attention and hope that vitamin D will mitigate SARS-CoV2 infection – based only on observational data.

You might argue against this point by saying vitamin D is natural and relatively innocuous, so who cares?

I offer three rebuttals to that point: Opportunity costs, distraction, and the insidious danger of poor critical appraisal skills. If you are burning money on vitamin D research, there is less available to study other important issues. If a patient is distracted by low vitamin D levels, she may pay less attention to her high body mass index or hypertension. And on the matter of critical appraisal, trust in medicine requires clinicians to be competent in critical appraisal. And these days, what could be more important than trust in medical professionals?

One major reason for the failure of persuasion of evidence is spin – or language that distracts from the primary endpoint. Here are two (of many) examples:

A meta-analysis of 50 vitamin D trials set out to study mortality. The authors found no significant difference in that primary endpoint. But the second sentence in their conclusion was that vitamin D supplements reduced the risk for cancer deaths by 15%. That’s a secondary endpoint in a study with nonsignificance in the primary endpoint. That is spin. This meta-analysis was completed before the Australian D-Health trial found that cancer deaths were 15% higher in the vitamin D arm, a difference that did not reach statistical significance.

The following example is worse: The authors of the VITAL trial, which found that vitamin D supplements had no effect on the primary endpoint of invasive cancer or cardiovascular disease, published a secondary analysis of the trial looking at a different endpoint: A composite incidence of metastatic and fatal invasive total cancer. They reported a 0.4% lower rate for the vitamin D group, a difference that barely made statistical significance at a P value of .04. 

But everyone knows the dangers of reanalyzing data with a new endpoint after you have seen the data. What’s more, even if this were a reasonable post hoc analysis, the results are neither clinically meaningful nor statistically robust.  Yet the fatally flawed paper has been viewed 60,000 times and picked up by 48 news outlets.

Another way to distract from nonsignificant primary outcomes is to nitpick the trials. The vitamin D dose wasn’t high enough, for instance. This might persuade me if there were one or two vitamin D trials, but there are hundreds of trials and meta-analyses, and their results are consistently null.
 

Conclusion: No, it is not hopeless

A nihilist would argue that fighting spin is futile. They would say you can’t fight incentives and business models. The incentive structure to publish is strong, and the journals and media know vitamin D studies garner attention – which is their currency.

I am not a nihilist and believe strongly that we must continue to teach critical appraisal and numerical literacy.

In fact, I would speculate that decades of poor critical appraisal by the medical profession have fostered outsized hope and created erroneous norms.

Imagine a counter-factual world in which clinicians have taught society that the human body is unlike an engine that can be repaired by fixing one part (i.e., the vitamin D level), that magic bullets (insulin) are rare, that most treatments fail, or that you can’t rely on association studies to prove efficacy.

In this world, people would be immune from spin and hype.

The norm would be that pills, supplements, and procedures are not what delivers good health. What delivers health is an amalgam of good luck, healthy habits, and lots of time spent outside playing in the sun.
 

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The vitamin D story exudes teaching points: It offers a master class in critical appraisal, connecting the concepts of biologic plausibility, flawed surrogate markers, confounded observational studies, and slews of randomized controlled trials (RCTs) showing no benefits on health outcomes.

Yet despite the utter lack of benefit seen in trials, the hype continues. And the pandemic has only enhanced this hype as an onslaught of papers have reported the association of low vitamin D levels and COVID-19 disease.

My questions are simple: Why doesn’t the evidence persuade people? How many nonsignificant trials do we need before researchers stop studying vitamin D, doctors stop (routinely) measuring levels, and patients stop wasting money on the unhelpful supplement? What are the implications for this lack of persuasion?

Before exploring these questions, I want to set out that symptomatic vitamin deficiencies of any sort ought to be corrected. 
 

Biologic plausibility and the pull of observational studies

It has long been known that vitamin D is crucial for bone health and that it can be produced in the skin with sun exposure. In the last decade, however, experts note that nearly every tissue and cell in our body has a vitamin D receptor. It then follows that if this many cells in the body can activate vitamin D, it must be vital for cardiovascular health, immune function, cancer prevention: basically, everything health related.

Oodles of observational studies have found that low serum levels of vitamin D correlate with higher mortality from all causes, cancer, cardiovascular disease, and now even COVID-19. Yet no matter the amount of statistical adjustment in these studies, we cannot know whether these associations are due to true causality.

The major issue is confounding: That is, people with low vitamin D levels have other conditions or diseases that lead to higher rates of ill health. Consider a patient with obesity, arthritis, and cognitive decline; this person is unlikely to do much exercise in the sun and may have low vitamin D levels. The low vitamin D level is simply a marker of overall poor health.
 

The randomized controlled trials tell a clear story

There are hundreds of vitamin D RCTs. The results simplify into one sentence: Vitamin D supplements do not improve health outcomes.

Here is a short summary of some recent studies.

VITAL, a massive (N > 25,000) RCT with 5 years of follow-up, compared vitamin D supplements to placebo and found no differences in the primary endpoints of cancer or cardiac events. Rates of death from any cause were nearly identical. Crucially, in subgroup analyses, the effects did not vary according to vitamin D levels at baseline.

The D-Health investigators randomly assigned more than 21,000 adults to vitamin D or placebo and after 5.7 years of follow-up reported no differences in the primary endpoint of overall mortality. There also were no differences in cardiovascular disease mortality.

Then you have the Mendelian randomized studies, which some have called nature’s RCT. These studies take advantage of the fact that some people are born with gene variations that predispose to low vitamin D levels. More than 60 Mendelian randomization studies have evaluated the consequences of lifelong genetically lowered vitamin D levels on various outcomes; most of these have found null effects.

Then there are the meta-analyses and systematic reviews. I loved the conclusion of this review of systematic reviews from the BMJ (emphasis mine):

“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.”

 

The failure to persuade

My original plan was to emphasize the power of the RCT. Despite strong associations of low vitamin D levels with poor outcomes, the trials show no benefit to treatment. This strongly suggests (or nearly proves) that low vitamin D levels are akin to premature ventricular complexes after myocardial infarction: a marker for risk but not a target for therapy.

But I now see the more important issue as why scientists, funders, clinicians, and patients are not persuaded by clear evidence. Every day in clinic I see patients on vitamin D supplements; the journals keep publishing vitamin D studies. The proponents of vitamin D remain positive. And lately there is outsized attention and hope that vitamin D will mitigate SARS-CoV2 infection – based only on observational data.

You might argue against this point by saying vitamin D is natural and relatively innocuous, so who cares?

I offer three rebuttals to that point: Opportunity costs, distraction, and the insidious danger of poor critical appraisal skills. If you are burning money on vitamin D research, there is less available to study other important issues. If a patient is distracted by low vitamin D levels, she may pay less attention to her high body mass index or hypertension. And on the matter of critical appraisal, trust in medicine requires clinicians to be competent in critical appraisal. And these days, what could be more important than trust in medical professionals?

One major reason for the failure of persuasion of evidence is spin – or language that distracts from the primary endpoint. Here are two (of many) examples:

A meta-analysis of 50 vitamin D trials set out to study mortality. The authors found no significant difference in that primary endpoint. But the second sentence in their conclusion was that vitamin D supplements reduced the risk for cancer deaths by 15%. That’s a secondary endpoint in a study with nonsignificance in the primary endpoint. That is spin. This meta-analysis was completed before the Australian D-Health trial found that cancer deaths were 15% higher in the vitamin D arm, a difference that did not reach statistical significance.

The following example is worse: The authors of the VITAL trial, which found that vitamin D supplements had no effect on the primary endpoint of invasive cancer or cardiovascular disease, published a secondary analysis of the trial looking at a different endpoint: A composite incidence of metastatic and fatal invasive total cancer. They reported a 0.4% lower rate for the vitamin D group, a difference that barely made statistical significance at a P value of .04. 

But everyone knows the dangers of reanalyzing data with a new endpoint after you have seen the data. What’s more, even if this were a reasonable post hoc analysis, the results are neither clinically meaningful nor statistically robust.  Yet the fatally flawed paper has been viewed 60,000 times and picked up by 48 news outlets.

Another way to distract from nonsignificant primary outcomes is to nitpick the trials. The vitamin D dose wasn’t high enough, for instance. This might persuade me if there were one or two vitamin D trials, but there are hundreds of trials and meta-analyses, and their results are consistently null.
 

Conclusion: No, it is not hopeless

A nihilist would argue that fighting spin is futile. They would say you can’t fight incentives and business models. The incentive structure to publish is strong, and the journals and media know vitamin D studies garner attention – which is their currency.

I am not a nihilist and believe strongly that we must continue to teach critical appraisal and numerical literacy.

In fact, I would speculate that decades of poor critical appraisal by the medical profession have fostered outsized hope and created erroneous norms.

Imagine a counter-factual world in which clinicians have taught society that the human body is unlike an engine that can be repaired by fixing one part (i.e., the vitamin D level), that magic bullets (insulin) are rare, that most treatments fail, or that you can’t rely on association studies to prove efficacy.

In this world, people would be immune from spin and hype.

The norm would be that pills, supplements, and procedures are not what delivers good health. What delivers health is an amalgam of good luck, healthy habits, and lots of time spent outside playing in the sun.
 

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The vitamin D story exudes teaching points: It offers a master class in critical appraisal, connecting the concepts of biologic plausibility, flawed surrogate markers, confounded observational studies, and slews of randomized controlled trials (RCTs) showing no benefits on health outcomes.

Yet despite the utter lack of benefit seen in trials, the hype continues. And the pandemic has only enhanced this hype as an onslaught of papers have reported the association of low vitamin D levels and COVID-19 disease.

My questions are simple: Why doesn’t the evidence persuade people? How many nonsignificant trials do we need before researchers stop studying vitamin D, doctors stop (routinely) measuring levels, and patients stop wasting money on the unhelpful supplement? What are the implications for this lack of persuasion?

Before exploring these questions, I want to set out that symptomatic vitamin deficiencies of any sort ought to be corrected. 
 

Biologic plausibility and the pull of observational studies

It has long been known that vitamin D is crucial for bone health and that it can be produced in the skin with sun exposure. In the last decade, however, experts note that nearly every tissue and cell in our body has a vitamin D receptor. It then follows that if this many cells in the body can activate vitamin D, it must be vital for cardiovascular health, immune function, cancer prevention: basically, everything health related.

Oodles of observational studies have found that low serum levels of vitamin D correlate with higher mortality from all causes, cancer, cardiovascular disease, and now even COVID-19. Yet no matter the amount of statistical adjustment in these studies, we cannot know whether these associations are due to true causality.

The major issue is confounding: That is, people with low vitamin D levels have other conditions or diseases that lead to higher rates of ill health. Consider a patient with obesity, arthritis, and cognitive decline; this person is unlikely to do much exercise in the sun and may have low vitamin D levels. The low vitamin D level is simply a marker of overall poor health.
 

The randomized controlled trials tell a clear story

There are hundreds of vitamin D RCTs. The results simplify into one sentence: Vitamin D supplements do not improve health outcomes.

Here is a short summary of some recent studies.

VITAL, a massive (N > 25,000) RCT with 5 years of follow-up, compared vitamin D supplements to placebo and found no differences in the primary endpoints of cancer or cardiac events. Rates of death from any cause were nearly identical. Crucially, in subgroup analyses, the effects did not vary according to vitamin D levels at baseline.

The D-Health investigators randomly assigned more than 21,000 adults to vitamin D or placebo and after 5.7 years of follow-up reported no differences in the primary endpoint of overall mortality. There also were no differences in cardiovascular disease mortality.

Then you have the Mendelian randomized studies, which some have called nature’s RCT. These studies take advantage of the fact that some people are born with gene variations that predispose to low vitamin D levels. More than 60 Mendelian randomization studies have evaluated the consequences of lifelong genetically lowered vitamin D levels on various outcomes; most of these have found null effects.

Then there are the meta-analyses and systematic reviews. I loved the conclusion of this review of systematic reviews from the BMJ (emphasis mine):

“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.”

 

The failure to persuade

My original plan was to emphasize the power of the RCT. Despite strong associations of low vitamin D levels with poor outcomes, the trials show no benefit to treatment. This strongly suggests (or nearly proves) that low vitamin D levels are akin to premature ventricular complexes after myocardial infarction: a marker for risk but not a target for therapy.

But I now see the more important issue as why scientists, funders, clinicians, and patients are not persuaded by clear evidence. Every day in clinic I see patients on vitamin D supplements; the journals keep publishing vitamin D studies. The proponents of vitamin D remain positive. And lately there is outsized attention and hope that vitamin D will mitigate SARS-CoV2 infection – based only on observational data.

You might argue against this point by saying vitamin D is natural and relatively innocuous, so who cares?

I offer three rebuttals to that point: Opportunity costs, distraction, and the insidious danger of poor critical appraisal skills. If you are burning money on vitamin D research, there is less available to study other important issues. If a patient is distracted by low vitamin D levels, she may pay less attention to her high body mass index or hypertension. And on the matter of critical appraisal, trust in medicine requires clinicians to be competent in critical appraisal. And these days, what could be more important than trust in medical professionals?

One major reason for the failure of persuasion of evidence is spin – or language that distracts from the primary endpoint. Here are two (of many) examples:

A meta-analysis of 50 vitamin D trials set out to study mortality. The authors found no significant difference in that primary endpoint. But the second sentence in their conclusion was that vitamin D supplements reduced the risk for cancer deaths by 15%. That’s a secondary endpoint in a study with nonsignificance in the primary endpoint. That is spin. This meta-analysis was completed before the Australian D-Health trial found that cancer deaths were 15% higher in the vitamin D arm, a difference that did not reach statistical significance.

The following example is worse: The authors of the VITAL trial, which found that vitamin D supplements had no effect on the primary endpoint of invasive cancer or cardiovascular disease, published a secondary analysis of the trial looking at a different endpoint: A composite incidence of metastatic and fatal invasive total cancer. They reported a 0.4% lower rate for the vitamin D group, a difference that barely made statistical significance at a P value of .04. 

But everyone knows the dangers of reanalyzing data with a new endpoint after you have seen the data. What’s more, even if this were a reasonable post hoc analysis, the results are neither clinically meaningful nor statistically robust.  Yet the fatally flawed paper has been viewed 60,000 times and picked up by 48 news outlets.

Another way to distract from nonsignificant primary outcomes is to nitpick the trials. The vitamin D dose wasn’t high enough, for instance. This might persuade me if there were one or two vitamin D trials, but there are hundreds of trials and meta-analyses, and their results are consistently null.
 

Conclusion: No, it is not hopeless

A nihilist would argue that fighting spin is futile. They would say you can’t fight incentives and business models. The incentive structure to publish is strong, and the journals and media know vitamin D studies garner attention – which is their currency.

I am not a nihilist and believe strongly that we must continue to teach critical appraisal and numerical literacy.

In fact, I would speculate that decades of poor critical appraisal by the medical profession have fostered outsized hope and created erroneous norms.

Imagine a counter-factual world in which clinicians have taught society that the human body is unlike an engine that can be repaired by fixing one part (i.e., the vitamin D level), that magic bullets (insulin) are rare, that most treatments fail, or that you can’t rely on association studies to prove efficacy.

In this world, people would be immune from spin and hype.

The norm would be that pills, supplements, and procedures are not what delivers good health. What delivers health is an amalgam of good luck, healthy habits, and lots of time spent outside playing in the sun.
 

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Junk (germs) in the trunk

It’s been a long drive, and you’ve got a long way to go. You pull into a rest stop to use the bathroom and get some food. Quick, which order do you do those things in?

If you’re not a crazy person, you’d use the bathroom and then get your food. Who would bring food into a dirty bathroom? That’s kind of gross. Most people would take care of business, grab food, then get back in the car, eating along the way. Unfortunately, if you’re searching for a sanitary eating environment, your car may not actually be much better than that bathroom, according to new research from Aston University in Birmingham, England.

Robert Couse-Baker/PxHere

Let’s start off with the good news. The steering wheels of the five used cars that were swabbed for bacteria were pretty clean. Definitely cleaner than either of the toilet seats analyzed, likely thanks to increased usage of sanitizer, courtesy of the current pandemic. It’s easy to wipe down the steering wheel. Things break down, though, once we look elsewhere. The interiors of the five cars all contained just as much, if not more, bacteria than the toilet seats, with fecal matter commonly appearing on the driver’s seat.

The car interiors were less than sanitary, but they paled in comparison with the real winner here: the trunk. In each of the five cars, bacteria levels there far exceeded those in the toilets, and included everyone’s favorites – Escherichia coli and Staphylococcus aureus.

So, snacking on a bag of chips as you drive along is probably okay, but the food that popped out of its bag and spent the last 5 minutes rolling around the back? Perhaps less okay. You may want to wash it. Or burn it. Or torch the entire car for good measure like we’re about to do. Next time we’ll buy a car without poop in it.
 

Shut the lid when you flush

Maybe you’ve never thought about this, but it’s actually extremely important to shut the toilet lid when you flush. Just think of all those germs flying around from the force of the flush. Is your toothbrush anywhere near the toilet? Ew. Those pesky little bacteria and viruses are everywhere, and we know we can’t really escape them, but we should really do our best once we’re made aware of where to find them.

Marco Verch/ccnull.de/CC by 2.0

It seems like a no-brainer these days since we’ve all been really focused on cleanliness during the pandemic, but according to a poll in the United Kingdom, 55% of the 2,000 participants said they don’t put the lid down while flushing.

The OnePoll survey commissioned by Harpic, a company that makes toilet-cleaning products, also advised that toilet water isn’t even completely clean after flushed several times and can still be contaminated with many germs. Company researchers took specialized pictures of flushing toilets and they looked like tiny little Fourth of July fireworks shows, minus the sparklers. The pictures proved that droplets can go all over the place, including on bathroom users.

“There has never been a more important time to take extra care around our homes, although the risks associated with germ spread in unhygienic bathrooms are high, the solution to keeping them clean is simple,” a Harpic researcher said. Since other studies have shown that coronavirus can be found in feces, it’s become increasingly important to keep ourselves and others safe. Fireworks are pretty, but not when they come out of your toilet.
 

The latest in MRI fashion

Do you see that photo just below? Looks like something you could buy at the Lego store, right? Well, it’s not. Nor is it the proverbial thinking cap come to life.

(Did someone just say “come to life”? That reminds us of our favorite scene from Frosty the Snowman.)

Cydney Scott/Boston University

Anywaaay, about the photo. That funny-looking chapeau is what we in the science business call a metamaterial.

Nope, metamaterials have nothing to do with Facebook parent company Meta. We checked. According to a statement from Boston University, they are engineered structures “created from small unit cells that might be unspectacular alone, but when grouped together in a precise way, get new superpowers not found in nature.”

Superpowers, eh? Who doesn’t want superpowers? Even if they come with a funny hat.

The unit cells, known as resonators, are just plastic tubes wrapped in copper wiring, but when they are grouped in an array and precisely arranged into a helmet, they can channel the magnetic field of the MRI machine during a scan. In theory, that would create “crisper images that can be captured at twice the normal speed,” Xin Zhang, PhD, and her team at BU’s Photonics Center explained in the university statement.

In the future, the metamaterial device could “be used in conjunction with cheaper low-field MRI machines to make the technology more widely available, particularly in the developing world,” they suggested. Or, like so many other superpowers, it could fall into the wrong hands. Like those of Lex Luthor. Or Mark Zuckerberg. Or Frosty the Snowman.
 

The highway of the mind

How fast can you think on your feet? Well, according to a recently published study, it could be a legitimate measure of intelligence. Here’s the science.

Epifantsev/Thinkstock

Researchers from the University of Würzburg in Germany and Indiana University have suggested that a person’s intelligence score measures the ability, based on certain neuronal networks and their communication structures, to switch between resting state and different task states.

The investigators set up a study to observe almost 800 people while they completed seven tasks. By monitoring brain activity with functional magnetic resonance imaging, the teams found that subjects who had higher intelligence scores required “less adjustment when switching between different cognitive states,” they said in a separate statement.

It comes down to the network architecture of their brains.

Kirsten Hilger, PhD, head of the German group, described it in terms of highways. The resting state of the brain is normal traffic. It’s always moving. Holiday traffic is the task. The ability to handle the increased flow of commuters is a function of the highway infrastructure. The better the infrastructure, the higher the intelligence.

So the next time you’re stuck in traffic, think how efficient your brain would be with such a task. The quicker, the better.

Junk (germs) in the trunk

It’s been a long drive, and you’ve got a long way to go. You pull into a rest stop to use the bathroom and get some food. Quick, which order do you do those things in?

If you’re not a crazy person, you’d use the bathroom and then get your food. Who would bring food into a dirty bathroom? That’s kind of gross. Most people would take care of business, grab food, then get back in the car, eating along the way. Unfortunately, if you’re searching for a sanitary eating environment, your car may not actually be much better than that bathroom, according to new research from Aston University in Birmingham, England.

Robert Couse-Baker/PxHere

Let’s start off with the good news. The steering wheels of the five used cars that were swabbed for bacteria were pretty clean. Definitely cleaner than either of the toilet seats analyzed, likely thanks to increased usage of sanitizer, courtesy of the current pandemic. It’s easy to wipe down the steering wheel. Things break down, though, once we look elsewhere. The interiors of the five cars all contained just as much, if not more, bacteria than the toilet seats, with fecal matter commonly appearing on the driver’s seat.

The car interiors were less than sanitary, but they paled in comparison with the real winner here: the trunk. In each of the five cars, bacteria levels there far exceeded those in the toilets, and included everyone’s favorites – Escherichia coli and Staphylococcus aureus.

So, snacking on a bag of chips as you drive along is probably okay, but the food that popped out of its bag and spent the last 5 minutes rolling around the back? Perhaps less okay. You may want to wash it. Or burn it. Or torch the entire car for good measure like we’re about to do. Next time we’ll buy a car without poop in it.
 

Shut the lid when you flush

Maybe you’ve never thought about this, but it’s actually extremely important to shut the toilet lid when you flush. Just think of all those germs flying around from the force of the flush. Is your toothbrush anywhere near the toilet? Ew. Those pesky little bacteria and viruses are everywhere, and we know we can’t really escape them, but we should really do our best once we’re made aware of where to find them.

Marco Verch/ccnull.de/CC by 2.0

It seems like a no-brainer these days since we’ve all been really focused on cleanliness during the pandemic, but according to a poll in the United Kingdom, 55% of the 2,000 participants said they don’t put the lid down while flushing.

The OnePoll survey commissioned by Harpic, a company that makes toilet-cleaning products, also advised that toilet water isn’t even completely clean after flushed several times and can still be contaminated with many germs. Company researchers took specialized pictures of flushing toilets and they looked like tiny little Fourth of July fireworks shows, minus the sparklers. The pictures proved that droplets can go all over the place, including on bathroom users.

“There has never been a more important time to take extra care around our homes, although the risks associated with germ spread in unhygienic bathrooms are high, the solution to keeping them clean is simple,” a Harpic researcher said. Since other studies have shown that coronavirus can be found in feces, it’s become increasingly important to keep ourselves and others safe. Fireworks are pretty, but not when they come out of your toilet.
 

The latest in MRI fashion

Do you see that photo just below? Looks like something you could buy at the Lego store, right? Well, it’s not. Nor is it the proverbial thinking cap come to life.

(Did someone just say “come to life”? That reminds us of our favorite scene from Frosty the Snowman.)

Cydney Scott/Boston University

Anywaaay, about the photo. That funny-looking chapeau is what we in the science business call a metamaterial.

Nope, metamaterials have nothing to do with Facebook parent company Meta. We checked. According to a statement from Boston University, they are engineered structures “created from small unit cells that might be unspectacular alone, but when grouped together in a precise way, get new superpowers not found in nature.”

Superpowers, eh? Who doesn’t want superpowers? Even if they come with a funny hat.

The unit cells, known as resonators, are just plastic tubes wrapped in copper wiring, but when they are grouped in an array and precisely arranged into a helmet, they can channel the magnetic field of the MRI machine during a scan. In theory, that would create “crisper images that can be captured at twice the normal speed,” Xin Zhang, PhD, and her team at BU’s Photonics Center explained in the university statement.

In the future, the metamaterial device could “be used in conjunction with cheaper low-field MRI machines to make the technology more widely available, particularly in the developing world,” they suggested. Or, like so many other superpowers, it could fall into the wrong hands. Like those of Lex Luthor. Or Mark Zuckerberg. Or Frosty the Snowman.
 

The highway of the mind

How fast can you think on your feet? Well, according to a recently published study, it could be a legitimate measure of intelligence. Here’s the science.

Epifantsev/Thinkstock

Researchers from the University of Würzburg in Germany and Indiana University have suggested that a person’s intelligence score measures the ability, based on certain neuronal networks and their communication structures, to switch between resting state and different task states.

The investigators set up a study to observe almost 800 people while they completed seven tasks. By monitoring brain activity with functional magnetic resonance imaging, the teams found that subjects who had higher intelligence scores required “less adjustment when switching between different cognitive states,” they said in a separate statement.

It comes down to the network architecture of their brains.

Kirsten Hilger, PhD, head of the German group, described it in terms of highways. The resting state of the brain is normal traffic. It’s always moving. Holiday traffic is the task. The ability to handle the increased flow of commuters is a function of the highway infrastructure. The better the infrastructure, the higher the intelligence.

So the next time you’re stuck in traffic, think how efficient your brain would be with such a task. The quicker, the better.

Junk (germs) in the trunk

It’s been a long drive, and you’ve got a long way to go. You pull into a rest stop to use the bathroom and get some food. Quick, which order do you do those things in?

If you’re not a crazy person, you’d use the bathroom and then get your food. Who would bring food into a dirty bathroom? That’s kind of gross. Most people would take care of business, grab food, then get back in the car, eating along the way. Unfortunately, if you’re searching for a sanitary eating environment, your car may not actually be much better than that bathroom, according to new research from Aston University in Birmingham, England.

Robert Couse-Baker/PxHere

Let’s start off with the good news. The steering wheels of the five used cars that were swabbed for bacteria were pretty clean. Definitely cleaner than either of the toilet seats analyzed, likely thanks to increased usage of sanitizer, courtesy of the current pandemic. It’s easy to wipe down the steering wheel. Things break down, though, once we look elsewhere. The interiors of the five cars all contained just as much, if not more, bacteria than the toilet seats, with fecal matter commonly appearing on the driver’s seat.

The car interiors were less than sanitary, but they paled in comparison with the real winner here: the trunk. In each of the five cars, bacteria levels there far exceeded those in the toilets, and included everyone’s favorites – Escherichia coli and Staphylococcus aureus.

So, snacking on a bag of chips as you drive along is probably okay, but the food that popped out of its bag and spent the last 5 minutes rolling around the back? Perhaps less okay. You may want to wash it. Or burn it. Or torch the entire car for good measure like we’re about to do. Next time we’ll buy a car without poop in it.
 

Shut the lid when you flush

Maybe you’ve never thought about this, but it’s actually extremely important to shut the toilet lid when you flush. Just think of all those germs flying around from the force of the flush. Is your toothbrush anywhere near the toilet? Ew. Those pesky little bacteria and viruses are everywhere, and we know we can’t really escape them, but we should really do our best once we’re made aware of where to find them.

Marco Verch/ccnull.de/CC by 2.0

It seems like a no-brainer these days since we’ve all been really focused on cleanliness during the pandemic, but according to a poll in the United Kingdom, 55% of the 2,000 participants said they don’t put the lid down while flushing.

The OnePoll survey commissioned by Harpic, a company that makes toilet-cleaning products, also advised that toilet water isn’t even completely clean after flushed several times and can still be contaminated with many germs. Company researchers took specialized pictures of flushing toilets and they looked like tiny little Fourth of July fireworks shows, minus the sparklers. The pictures proved that droplets can go all over the place, including on bathroom users.

“There has never been a more important time to take extra care around our homes, although the risks associated with germ spread in unhygienic bathrooms are high, the solution to keeping them clean is simple,” a Harpic researcher said. Since other studies have shown that coronavirus can be found in feces, it’s become increasingly important to keep ourselves and others safe. Fireworks are pretty, but not when they come out of your toilet.
 

The latest in MRI fashion

Do you see that photo just below? Looks like something you could buy at the Lego store, right? Well, it’s not. Nor is it the proverbial thinking cap come to life.

(Did someone just say “come to life”? That reminds us of our favorite scene from Frosty the Snowman.)

Cydney Scott/Boston University

Anywaaay, about the photo. That funny-looking chapeau is what we in the science business call a metamaterial.

Nope, metamaterials have nothing to do with Facebook parent company Meta. We checked. According to a statement from Boston University, they are engineered structures “created from small unit cells that might be unspectacular alone, but when grouped together in a precise way, get new superpowers not found in nature.”

Superpowers, eh? Who doesn’t want superpowers? Even if they come with a funny hat.

The unit cells, known as resonators, are just plastic tubes wrapped in copper wiring, but when they are grouped in an array and precisely arranged into a helmet, they can channel the magnetic field of the MRI machine during a scan. In theory, that would create “crisper images that can be captured at twice the normal speed,” Xin Zhang, PhD, and her team at BU’s Photonics Center explained in the university statement.

In the future, the metamaterial device could “be used in conjunction with cheaper low-field MRI machines to make the technology more widely available, particularly in the developing world,” they suggested. Or, like so many other superpowers, it could fall into the wrong hands. Like those of Lex Luthor. Or Mark Zuckerberg. Or Frosty the Snowman.
 

The highway of the mind

How fast can you think on your feet? Well, according to a recently published study, it could be a legitimate measure of intelligence. Here’s the science.

Epifantsev/Thinkstock

Researchers from the University of Würzburg in Germany and Indiana University have suggested that a person’s intelligence score measures the ability, based on certain neuronal networks and their communication structures, to switch between resting state and different task states.

The investigators set up a study to observe almost 800 people while they completed seven tasks. By monitoring brain activity with functional magnetic resonance imaging, the teams found that subjects who had higher intelligence scores required “less adjustment when switching between different cognitive states,” they said in a separate statement.

It comes down to the network architecture of their brains.

Kirsten Hilger, PhD, head of the German group, described it in terms of highways. The resting state of the brain is normal traffic. It’s always moving. Holiday traffic is the task. The ability to handle the increased flow of commuters is a function of the highway infrastructure. The better the infrastructure, the higher the intelligence.

So the next time you’re stuck in traffic, think how efficient your brain would be with such a task. The quicker, the better.

Gallbladder duplication is a congenital abnormality of the hepatobiliary system and often is not considered in the evaluation of a patient with right upper quadrant pain. Accuracy of the most commonly used imaging study to assess for biliary disease, abdominal ultrasound, is highly dependent on the skills of the ultrasonographer, and given its relative rarity, this condition is often not considered prior to planned cholecystectomy.¹ Small case reviews found that < 50% of gallbladder duplications are diagnosed preoperatively despite use of ultrasound or computed tomography (CT) scan.^2-4 Failure to recognize duplicate gallbladder anatomy in symptomatic patients may result in incomplete surgical management, an increase in perioperative complications, and years of morbidity due to unresolved symptoms. Once a patient has had a cholecystectomy, symptoms are presumed to be due to a nonbiliary etiology and an extensive, often repetitive, workup is pursued before “repeat cholecystectomy” is considered.⁵

Case Presentation

A 63-year-old man was referred to gastroenterology for recurrent episodic right upper quadrant pain. He reported intermittent both right and left upper abdominal pain that was variable in quality. At times it was associated with an empty stomach prior to meals; at other times, onset was 30 to 60 minutes after meals. The patient also reported significant flatulence and bloating and intermittent loose stools. Sixteen years before, he underwent a laparoscopic cholecystectomy. He reported that the pain he experienced before the cholecystectomy never resolved after surgery but occurred less frequently. For the next 16 years, the patient did not seek evaluation of his ongoing but infrequent symptoms until his pain became a daily occurrence. The patient’s surgical history included a remote open vagotomy and antrectomy for peptic ulcer disease, laparoscopic appendectomy, and a laparoscopic cholecystectomy for reported biliary colic.

The gastroenterology evaluation included a colonoscopy and esophagogastroduodenoscopy (EGD); both were benign and without findings specific to identify the etiology for the patient’s pain. The patient was given a course of rifaximin 1200 mg daily for 7 days for possible bacterial overgrowth and placed on a proton pump inhibitor twice daily. Neither of these interventions helped resolve the patient’s symptoms. Further workup was pursued by gastroenterology to include a right upper quadrant ultrasound that showed a structure most consistent with a small gallbladder containing a small polyp vs stone. Magnetic resonance cholangiopancreatography (MRCP) also was performed and showed the presence of a small gallbladder with a small 2-mm filling defect and an otherwise benign biliary tree. MRCP images and EGD documented a Billroth 1 reconstruction at the time of his remote antrectomy and vagotomy (Figure 1).

Discussion

The first reported human case of gallbladder duplication was noted in a sacrificial victim of Emperor Augustus in 31 BCE. Sherren reported the first documented case of double accessory gallbladder in a living human in 1911.^1,6 Though the exact incidence of gallbladder duplication is not fully known due to primary documentation from case reports, incidence is approximately 1 in 4000 to 5000 people. It was first formally classified by Boyden in 1926.⁷ Further anatomic classification based on morphology and embryogenesis was delineated by Harlaftis and colleagues in 1977, establishing type 1 and 2 structures of a duplicated gallbladder.⁸ Type 1 duplicated gallbladder anatomy shares a single cystic duct, whereas in type 2 each gallbladder has its own cystic duct. Later reports and studies identified triple gallbladders as well as trabecular variants with the most common classification used currently being the modified Harlaftis classification.^9,10

The case presented here most likely represents either a Y-shaped type 1 primordial gallbladder or a type 2 accessory gallbladder based on historical data and intraoperative cholangiogram findings at the time of repeat cholecystectomy. Gallbladder duplication is clinically indistinguishable from regular gallbladder pathology preoperatively and can only be identified on imaging or intraoperatively.¹¹ Prior case reports and studies have found that it is frequently missed on preoperative abdominal ultrasonography and CT in up to 50% of cases.^12-14

The differential diagnosis of gallbladder duplication seen on preoperative imaging includes a gallbladder diverticulum, choledochal cyst, focal adenonomyomatosis, Phrygian cap, or folded gallbladder.^1,2 Historically, the most definitive test for gallbladder duplication has been either intraoperative cholangiography, which can also clarify biliary anatomy, or endoscopic retrograde cholangiopancreatography with cholangiography.^1,3 The debate over routine use of intraoperative cholangiography has been ongoing for the past several decades.¹⁵ Though intraoperative cholangiogram remains one of the most definitive tests for gallbladder duplication, given the overall low incidence of this variant, recommendation for routine intraoperative cholangiography solely to rule out gallbladder duplication cannot be definitively recommended based on our review of the literature. Currently, preoperative MRCP is the study of choice when there is concern from historical facts or from other imaging of gallbladder duplication as it is noninvasive and has a high degree of detail, particularly with 3D reconstructions.^14,16 At the time of surgery, the most critical step to avoid inadvertent ductal injury is clear visualization of ductal anatomy and obtaining the critical view of safety.¹⁷ Though this will also assist in identifying some cases of gallbladder duplication, given the great variation of duplication, it will not prevent missing some variants. In our case, extensive local scarring from the patient’s prior antrectomy and vagotomy along with lack of the use of intraoperative cholangiography likely contributed to missing his duplication at the time of his index cholecystectomy.

Undiagnosed gallbladder duplication can lead to additional morbidity related to common entities associated with gallbladder pathology, such as biliary colic, cholecystitis, cholangitis, and pancreatitis. Additionally, case reports in the literature have documented more rare associations, such as empyema, carcinoma, cholecystoenteric fistula, and torsion, all associated with a duplicated gallbladder.^18-21 Once identified pre- or intraoperatively, it is generally recommended that all gallbladders be removed in symptomatic patients and that intraoperative cholangiography be done to assure complete resection of the duplicated gallbladders and to avoid injury to the biliary trees.^22-25

Conclusions

Gallbladder duplication and other congenital biliary anatomic variations should be considered before a biliary operation and included in the differential diagnosis when evaluating patients who have clinical symptoms consistent with biliary pathology. In addition, intraoperative cholangiogram should be performed during cholecystectomy if the inferior liver edge cannot be visualized well, as in the case of this patient where a prior foregut operation resulted in extensive adhesive disease. Intraoperative cholangiogram also should be considered in patients whose preoperative imaging does not visualize the right upper quadrant well due to patient habitus. Doing so may identify gallbladder duplication and allow for complete cholecystectomy as well as proper identification and management of cystic duct variants. Awareness and consideration of duplicated biliary variants can help prevent intraoperative complications related to biliary anomalies and avoid the morbidity related to recurrent biliary disease and the need for repeat operative procedures.

Acknowledgments

We extend our thanks to Veterans Affairs Puget Sound Healthcare System and the Departments of Surgery and Radiology for their support of this case report, and Lorrie Langdale, MD, and Roger Tatum, MD, for their mentorship of this project

Gallbladder duplication is a congenital abnormality of the hepatobiliary system and often is not considered in the evaluation of a patient with right upper quadrant pain. Accuracy of the most commonly used imaging study to assess for biliary disease, abdominal ultrasound, is highly dependent on the skills of the ultrasonographer, and given its relative rarity, this condition is often not considered prior to planned cholecystectomy.¹ Small case reviews found that < 50% of gallbladder duplications are diagnosed preoperatively despite use of ultrasound or computed tomography (CT) scan.^2-4 Failure to recognize duplicate gallbladder anatomy in symptomatic patients may result in incomplete surgical management, an increase in perioperative complications, and years of morbidity due to unresolved symptoms. Once a patient has had a cholecystectomy, symptoms are presumed to be due to a nonbiliary etiology and an extensive, often repetitive, workup is pursued before “repeat cholecystectomy” is considered.⁵

Case Presentation

A 63-year-old man was referred to gastroenterology for recurrent episodic right upper quadrant pain. He reported intermittent both right and left upper abdominal pain that was variable in quality. At times it was associated with an empty stomach prior to meals; at other times, onset was 30 to 60 minutes after meals. The patient also reported significant flatulence and bloating and intermittent loose stools. Sixteen years before, he underwent a laparoscopic cholecystectomy. He reported that the pain he experienced before the cholecystectomy never resolved after surgery but occurred less frequently. For the next 16 years, the patient did not seek evaluation of his ongoing but infrequent symptoms until his pain became a daily occurrence. The patient’s surgical history included a remote open vagotomy and antrectomy for peptic ulcer disease, laparoscopic appendectomy, and a laparoscopic cholecystectomy for reported biliary colic.

The gastroenterology evaluation included a colonoscopy and esophagogastroduodenoscopy (EGD); both were benign and without findings specific to identify the etiology for the patient’s pain. The patient was given a course of rifaximin 1200 mg daily for 7 days for possible bacterial overgrowth and placed on a proton pump inhibitor twice daily. Neither of these interventions helped resolve the patient’s symptoms. Further workup was pursued by gastroenterology to include a right upper quadrant ultrasound that showed a structure most consistent with a small gallbladder containing a small polyp vs stone. Magnetic resonance cholangiopancreatography (MRCP) also was performed and showed the presence of a small gallbladder with a small 2-mm filling defect and an otherwise benign biliary tree. MRCP images and EGD documented a Billroth 1 reconstruction at the time of his remote antrectomy and vagotomy (Figure 1).

Discussion

The first reported human case of gallbladder duplication was noted in a sacrificial victim of Emperor Augustus in 31 BCE. Sherren reported the first documented case of double accessory gallbladder in a living human in 1911.^1,6 Though the exact incidence of gallbladder duplication is not fully known due to primary documentation from case reports, incidence is approximately 1 in 4000 to 5000 people. It was first formally classified by Boyden in 1926.⁷ Further anatomic classification based on morphology and embryogenesis was delineated by Harlaftis and colleagues in 1977, establishing type 1 and 2 structures of a duplicated gallbladder.⁸ Type 1 duplicated gallbladder anatomy shares a single cystic duct, whereas in type 2 each gallbladder has its own cystic duct. Later reports and studies identified triple gallbladders as well as trabecular variants with the most common classification used currently being the modified Harlaftis classification.^9,10

The case presented here most likely represents either a Y-shaped type 1 primordial gallbladder or a type 2 accessory gallbladder based on historical data and intraoperative cholangiogram findings at the time of repeat cholecystectomy. Gallbladder duplication is clinically indistinguishable from regular gallbladder pathology preoperatively and can only be identified on imaging or intraoperatively.¹¹ Prior case reports and studies have found that it is frequently missed on preoperative abdominal ultrasonography and CT in up to 50% of cases.^12-14

The differential diagnosis of gallbladder duplication seen on preoperative imaging includes a gallbladder diverticulum, choledochal cyst, focal adenonomyomatosis, Phrygian cap, or folded gallbladder.^1,2 Historically, the most definitive test for gallbladder duplication has been either intraoperative cholangiography, which can also clarify biliary anatomy, or endoscopic retrograde cholangiopancreatography with cholangiography.^1,3 The debate over routine use of intraoperative cholangiography has been ongoing for the past several decades.¹⁵ Though intraoperative cholangiogram remains one of the most definitive tests for gallbladder duplication, given the overall low incidence of this variant, recommendation for routine intraoperative cholangiography solely to rule out gallbladder duplication cannot be definitively recommended based on our review of the literature. Currently, preoperative MRCP is the study of choice when there is concern from historical facts or from other imaging of gallbladder duplication as it is noninvasive and has a high degree of detail, particularly with 3D reconstructions.^14,16 At the time of surgery, the most critical step to avoid inadvertent ductal injury is clear visualization of ductal anatomy and obtaining the critical view of safety.¹⁷ Though this will also assist in identifying some cases of gallbladder duplication, given the great variation of duplication, it will not prevent missing some variants. In our case, extensive local scarring from the patient’s prior antrectomy and vagotomy along with lack of the use of intraoperative cholangiography likely contributed to missing his duplication at the time of his index cholecystectomy.

Undiagnosed gallbladder duplication can lead to additional morbidity related to common entities associated with gallbladder pathology, such as biliary colic, cholecystitis, cholangitis, and pancreatitis. Additionally, case reports in the literature have documented more rare associations, such as empyema, carcinoma, cholecystoenteric fistula, and torsion, all associated with a duplicated gallbladder.^18-21 Once identified pre- or intraoperatively, it is generally recommended that all gallbladders be removed in symptomatic patients and that intraoperative cholangiography be done to assure complete resection of the duplicated gallbladders and to avoid injury to the biliary trees.^22-25

Conclusions

Gallbladder duplication and other congenital biliary anatomic variations should be considered before a biliary operation and included in the differential diagnosis when evaluating patients who have clinical symptoms consistent with biliary pathology. In addition, intraoperative cholangiogram should be performed during cholecystectomy if the inferior liver edge cannot be visualized well, as in the case of this patient where a prior foregut operation resulted in extensive adhesive disease. Intraoperative cholangiogram also should be considered in patients whose preoperative imaging does not visualize the right upper quadrant well due to patient habitus. Doing so may identify gallbladder duplication and allow for complete cholecystectomy as well as proper identification and management of cystic duct variants. Awareness and consideration of duplicated biliary variants can help prevent intraoperative complications related to biliary anomalies and avoid the morbidity related to recurrent biliary disease and the need for repeat operative procedures.

Acknowledgments

We extend our thanks to Veterans Affairs Puget Sound Healthcare System and the Departments of Surgery and Radiology for their support of this case report, and Lorrie Langdale, MD, and Roger Tatum, MD, for their mentorship of this project

Gallbladder duplication is a congenital abnormality of the hepatobiliary system and often is not considered in the evaluation of a patient with right upper quadrant pain. Accuracy of the most commonly used imaging study to assess for biliary disease, abdominal ultrasound, is highly dependent on the skills of the ultrasonographer, and given its relative rarity, this condition is often not considered prior to planned cholecystectomy.¹ Small case reviews found that < 50% of gallbladder duplications are diagnosed preoperatively despite use of ultrasound or computed tomography (CT) scan.^2-4 Failure to recognize duplicate gallbladder anatomy in symptomatic patients may result in incomplete surgical management, an increase in perioperative complications, and years of morbidity due to unresolved symptoms. Once a patient has had a cholecystectomy, symptoms are presumed to be due to a nonbiliary etiology and an extensive, often repetitive, workup is pursued before “repeat cholecystectomy” is considered.⁵

Case Presentation

A 63-year-old man was referred to gastroenterology for recurrent episodic right upper quadrant pain. He reported intermittent both right and left upper abdominal pain that was variable in quality. At times it was associated with an empty stomach prior to meals; at other times, onset was 30 to 60 minutes after meals. The patient also reported significant flatulence and bloating and intermittent loose stools. Sixteen years before, he underwent a laparoscopic cholecystectomy. He reported that the pain he experienced before the cholecystectomy never resolved after surgery but occurred less frequently. For the next 16 years, the patient did not seek evaluation of his ongoing but infrequent symptoms until his pain became a daily occurrence. The patient’s surgical history included a remote open vagotomy and antrectomy for peptic ulcer disease, laparoscopic appendectomy, and a laparoscopic cholecystectomy for reported biliary colic.

The gastroenterology evaluation included a colonoscopy and esophagogastroduodenoscopy (EGD); both were benign and without findings specific to identify the etiology for the patient’s pain. The patient was given a course of rifaximin 1200 mg daily for 7 days for possible bacterial overgrowth and placed on a proton pump inhibitor twice daily. Neither of these interventions helped resolve the patient’s symptoms. Further workup was pursued by gastroenterology to include a right upper quadrant ultrasound that showed a structure most consistent with a small gallbladder containing a small polyp vs stone. Magnetic resonance cholangiopancreatography (MRCP) also was performed and showed the presence of a small gallbladder with a small 2-mm filling defect and an otherwise benign biliary tree. MRCP images and EGD documented a Billroth 1 reconstruction at the time of his remote antrectomy and vagotomy (Figure 1).

Discussion

The first reported human case of gallbladder duplication was noted in a sacrificial victim of Emperor Augustus in 31 BCE. Sherren reported the first documented case of double accessory gallbladder in a living human in 1911.^1,6 Though the exact incidence of gallbladder duplication is not fully known due to primary documentation from case reports, incidence is approximately 1 in 4000 to 5000 people. It was first formally classified by Boyden in 1926.⁷ Further anatomic classification based on morphology and embryogenesis was delineated by Harlaftis and colleagues in 1977, establishing type 1 and 2 structures of a duplicated gallbladder.⁸ Type 1 duplicated gallbladder anatomy shares a single cystic duct, whereas in type 2 each gallbladder has its own cystic duct. Later reports and studies identified triple gallbladders as well as trabecular variants with the most common classification used currently being the modified Harlaftis classification.^9,10

The case presented here most likely represents either a Y-shaped type 1 primordial gallbladder or a type 2 accessory gallbladder based on historical data and intraoperative cholangiogram findings at the time of repeat cholecystectomy. Gallbladder duplication is clinically indistinguishable from regular gallbladder pathology preoperatively and can only be identified on imaging or intraoperatively.¹¹ Prior case reports and studies have found that it is frequently missed on preoperative abdominal ultrasonography and CT in up to 50% of cases.^12-14

The differential diagnosis of gallbladder duplication seen on preoperative imaging includes a gallbladder diverticulum, choledochal cyst, focal adenonomyomatosis, Phrygian cap, or folded gallbladder.^1,2 Historically, the most definitive test for gallbladder duplication has been either intraoperative cholangiography, which can also clarify biliary anatomy, or endoscopic retrograde cholangiopancreatography with cholangiography.^1,3 The debate over routine use of intraoperative cholangiography has been ongoing for the past several decades.¹⁵ Though intraoperative cholangiogram remains one of the most definitive tests for gallbladder duplication, given the overall low incidence of this variant, recommendation for routine intraoperative cholangiography solely to rule out gallbladder duplication cannot be definitively recommended based on our review of the literature. Currently, preoperative MRCP is the study of choice when there is concern from historical facts or from other imaging of gallbladder duplication as it is noninvasive and has a high degree of detail, particularly with 3D reconstructions.^14,16 At the time of surgery, the most critical step to avoid inadvertent ductal injury is clear visualization of ductal anatomy and obtaining the critical view of safety.¹⁷ Though this will also assist in identifying some cases of gallbladder duplication, given the great variation of duplication, it will not prevent missing some variants. In our case, extensive local scarring from the patient’s prior antrectomy and vagotomy along with lack of the use of intraoperative cholangiography likely contributed to missing his duplication at the time of his index cholecystectomy.

Undiagnosed gallbladder duplication can lead to additional morbidity related to common entities associated with gallbladder pathology, such as biliary colic, cholecystitis, cholangitis, and pancreatitis. Additionally, case reports in the literature have documented more rare associations, such as empyema, carcinoma, cholecystoenteric fistula, and torsion, all associated with a duplicated gallbladder.^18-21 Once identified pre- or intraoperatively, it is generally recommended that all gallbladders be removed in symptomatic patients and that intraoperative cholangiography be done to assure complete resection of the duplicated gallbladders and to avoid injury to the biliary trees.^22-25

Conclusions

Gallbladder duplication and other congenital biliary anatomic variations should be considered before a biliary operation and included in the differential diagnosis when evaluating patients who have clinical symptoms consistent with biliary pathology. In addition, intraoperative cholangiogram should be performed during cholecystectomy if the inferior liver edge cannot be visualized well, as in the case of this patient where a prior foregut operation resulted in extensive adhesive disease. Intraoperative cholangiogram also should be considered in patients whose preoperative imaging does not visualize the right upper quadrant well due to patient habitus. Doing so may identify gallbladder duplication and allow for complete cholecystectomy as well as proper identification and management of cystic duct variants. Awareness and consideration of duplicated biliary variants can help prevent intraoperative complications related to biliary anomalies and avoid the morbidity related to recurrent biliary disease and the need for repeat operative procedures.

Acknowledgments

We extend our thanks to Veterans Affairs Puget Sound Healthcare System and the Departments of Surgery and Radiology for their support of this case report, and Lorrie Langdale, MD, and Roger Tatum, MD, for their mentorship of this project

Three physicians with the Food and Drug Administration suggest in a recent JAMA Oncology viewpoint article that it might be time to give drug companies a deadline to meet accelerated approval requirements, as is done in other countries.

The FDA launched its accelerated approval program in 1992 in response to the AIDS crisis, but the bulk of approvals since then have been for cancer drugs, wrote the authors who included Gautam U. Mehta, MD, a clinical reviewer with the FDA’s Center for Drug Evaluation and Research; R. Angelo de Claro, MD, associate director of the FDA’s Global Clinical Sciences division within the Oncology Center of Excellence; and Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

Accelerated approvals are typically granted in oncology based on overall response rate with a requirement that companies confirm that there’s actually a clinical benefit in postmarketing studies.

The system has inspired European nations and Australia to launch their own programs, but with a key difference: Conditional approvals expire within 1 year or 2.

To be reinstated and remain on the market, companies have to submit a timeline for when they’ll meet their outstanding obligations and demonstrate that the benefit of leaving their product on the market outweighs the risk.

The approach puts “the onus of timely completion of confirmatory trials and verification of benefit” on the drug maker. In the meantime, the system limits “public exposure to stale claims of effectiveness that cannot be expeditiously substantiated,” Dr. Mehta and colleagues wrote.

There aren’t any deadlines in the United States, however, so the FDA has “to initiate a resource-intensive withdrawal process” when proof of clinical benefit is not forthcoming, they said.

In the United States, only 14 of 167 oncology indications granted accelerated approval since 1992 were withdrawn voluntarily and one was withdrawn by FDA request, and one was forced by the agency. The median time from accelerated approval to withdrawal was 8.8 years.

The actual withdrawal process itself took 11 months when bevacizumab’s breast cancer indication was canceled in 2011.

The authors didn’t call for change outright, but they did say that “future discussions of the accelerated approval program in the U.S.” will seek “to coordinate regulatory processes” with other countries, with an eye towards building “harmony between” agencies.

Among other targets for possible harmonization, they noted that only new molecular entities are eligible for accelerated approval in Europe, whereas supplemental indications are also eligible in the United States

Europe also requires a risk-benefit assessment for conditional approvals, which “has led to relatively few approvals based on single-arm clinical trial data,” the authors said.

Dr. Mehta, Dr. de Claro, and Dr. Pazdur had no conflicts of interest.

Three physicians with the Food and Drug Administration suggest in a recent JAMA Oncology viewpoint article that it might be time to give drug companies a deadline to meet accelerated approval requirements, as is done in other countries.

The FDA launched its accelerated approval program in 1992 in response to the AIDS crisis, but the bulk of approvals since then have been for cancer drugs, wrote the authors who included Gautam U. Mehta, MD, a clinical reviewer with the FDA’s Center for Drug Evaluation and Research; R. Angelo de Claro, MD, associate director of the FDA’s Global Clinical Sciences division within the Oncology Center of Excellence; and Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

Accelerated approvals are typically granted in oncology based on overall response rate with a requirement that companies confirm that there’s actually a clinical benefit in postmarketing studies.

The system has inspired European nations and Australia to launch their own programs, but with a key difference: Conditional approvals expire within 1 year or 2.

To be reinstated and remain on the market, companies have to submit a timeline for when they’ll meet their outstanding obligations and demonstrate that the benefit of leaving their product on the market outweighs the risk.

The approach puts “the onus of timely completion of confirmatory trials and verification of benefit” on the drug maker. In the meantime, the system limits “public exposure to stale claims of effectiveness that cannot be expeditiously substantiated,” Dr. Mehta and colleagues wrote.

There aren’t any deadlines in the United States, however, so the FDA has “to initiate a resource-intensive withdrawal process” when proof of clinical benefit is not forthcoming, they said.

In the United States, only 14 of 167 oncology indications granted accelerated approval since 1992 were withdrawn voluntarily and one was withdrawn by FDA request, and one was forced by the agency. The median time from accelerated approval to withdrawal was 8.8 years.

The actual withdrawal process itself took 11 months when bevacizumab’s breast cancer indication was canceled in 2011.

The authors didn’t call for change outright, but they did say that “future discussions of the accelerated approval program in the U.S.” will seek “to coordinate regulatory processes” with other countries, with an eye towards building “harmony between” agencies.

Among other targets for possible harmonization, they noted that only new molecular entities are eligible for accelerated approval in Europe, whereas supplemental indications are also eligible in the United States

Europe also requires a risk-benefit assessment for conditional approvals, which “has led to relatively few approvals based on single-arm clinical trial data,” the authors said.

Dr. Mehta, Dr. de Claro, and Dr. Pazdur had no conflicts of interest.

Three physicians with the Food and Drug Administration suggest in a recent JAMA Oncology viewpoint article that it might be time to give drug companies a deadline to meet accelerated approval requirements, as is done in other countries.

The FDA launched its accelerated approval program in 1992 in response to the AIDS crisis, but the bulk of approvals since then have been for cancer drugs, wrote the authors who included Gautam U. Mehta, MD, a clinical reviewer with the FDA’s Center for Drug Evaluation and Research; R. Angelo de Claro, MD, associate director of the FDA’s Global Clinical Sciences division within the Oncology Center of Excellence; and Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

Accelerated approvals are typically granted in oncology based on overall response rate with a requirement that companies confirm that there’s actually a clinical benefit in postmarketing studies.

The system has inspired European nations and Australia to launch their own programs, but with a key difference: Conditional approvals expire within 1 year or 2.

To be reinstated and remain on the market, companies have to submit a timeline for when they’ll meet their outstanding obligations and demonstrate that the benefit of leaving their product on the market outweighs the risk.

The approach puts “the onus of timely completion of confirmatory trials and verification of benefit” on the drug maker. In the meantime, the system limits “public exposure to stale claims of effectiveness that cannot be expeditiously substantiated,” Dr. Mehta and colleagues wrote.

There aren’t any deadlines in the United States, however, so the FDA has “to initiate a resource-intensive withdrawal process” when proof of clinical benefit is not forthcoming, they said.

In the United States, only 14 of 167 oncology indications granted accelerated approval since 1992 were withdrawn voluntarily and one was withdrawn by FDA request, and one was forced by the agency. The median time from accelerated approval to withdrawal was 8.8 years.

The actual withdrawal process itself took 11 months when bevacizumab’s breast cancer indication was canceled in 2011.

The authors didn’t call for change outright, but they did say that “future discussions of the accelerated approval program in the U.S.” will seek “to coordinate regulatory processes” with other countries, with an eye towards building “harmony between” agencies.

Among other targets for possible harmonization, they noted that only new molecular entities are eligible for accelerated approval in Europe, whereas supplemental indications are also eligible in the United States

Europe also requires a risk-benefit assessment for conditional approvals, which “has led to relatively few approvals based on single-arm clinical trial data,” the authors said.

Dr. Mehta, Dr. de Claro, and Dr. Pazdur had no conflicts of interest.