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Maria A. Oquendo, MD, PhD, on the state of psychiatry
For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).
Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?
Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.
Dr. Aftab: What do you see as some of the strengths of our profession?
Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.
Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?
Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.
Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?
Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.
Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?
Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.
For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).
Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?
Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.
Dr. Aftab: What do you see as some of the strengths of our profession?
Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.
Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?
Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.
Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?
Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.
Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?
Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.
For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).
Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?
Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.
Dr. Aftab: What do you see as some of the strengths of our profession?
Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.
Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?
Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.
Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?
Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.
Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?
Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.
Placebo beat risankizumab in adults with severe asthma
Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.
The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.
Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.
Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
Study details
Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.
The mean age of the patients was 53 years; 66.5% of the patients were women.
Disappointing results
In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).
Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV1 after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
Further trials unwarranted
“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.
“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.
He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
Caution with investigating biologicals
Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.
“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.
Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.
The clinical trial was sponsored and funded by BI/AbbVie.
A version of this article first appeared on Medscape.com.
Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.
The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.
Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.
Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
Study details
Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.
The mean age of the patients was 53 years; 66.5% of the patients were women.
Disappointing results
In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).
Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV1 after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
Further trials unwarranted
“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.
“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.
He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
Caution with investigating biologicals
Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.
“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.
Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.
The clinical trial was sponsored and funded by BI/AbbVie.
A version of this article first appeared on Medscape.com.
Placebo treatment was found to be superior to treatment with risankizumab with respect to time to first asthma worsening and annualized rate of asthma worsening for adults with severe persistent asthma in a phase 2a clinical trial.
The randomized, double-blind, 24-week, parallel group, multicenter trial assessed risankizumab efficacy and safety in 214 adults with severe persistent asthma. The results were reported in The New England Journal of Medicine.
Risankizumab is a humanized, monoclonal antibody directed against subunit p19 of interleukin-23. It is approved for the treatment of moderate to severe psoriasis.
Interleukin-23 has been implicated in airway inflammation mediated by type 2 and type 17 cytokines. Noting that inhibition of interleukin-23 is effective in the treatment of psoriasis and Crohn’s disease, Christopher E. Brightling, MD, and colleagues investigated whether targeting interleukin-23 in asthma patients would improve disease control and reduce airway inflammation.
Study details
Patients received either 90 mg of risankizumab (subcutaneous) (n = 105) or placebo (n = 109) once every 4 weeks. Time to first asthma worsening was the primary endpoint. Worsening was defined as decline from baseline on 2 or more consecutive days. Deterioration was defined as a decrease of at least 30% in the morning peak expiratory flow or an increase from baseline of at least 50% in rescue medication puffs over 24 hours. In addition, a severe asthma exacerbation or an increase of 0.75 or more points on the five-item Asthma Control Questionnaire (scores range from 0 to 6, with higher scores indicating less control) were considered to be evidence of worsening. Annualized rate of asthma worsening was a secondary endpoint.
The mean age of the patients was 53 years; 66.5% of the patients were women.
Disappointing results
In the risankizumab group, median time to first asthma worsening was 40 days, significantly worse than the 86 days reported for the placebo group (hazard ratio, 1.46; 95% confidence interval, 1.05-2.04; P = .03). For annualized asthma worsening, the rate ratio for the comparison of risankizumab with placebo was 1.49 (95% CI, 1.12-1.99).
Among key secondary endpoints, the adjusted mean change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 24 was –0.05 L in the risankizumab group and –0.01 L in the placebo group. The adjusted mean change in FEV1 after bronchodilator use from baseline to week 24 was –0.10 L in the risankizumab group and –0.03 L in the placebo group. Sputum transcriptomic pathway analysis showed that genes involved in the activation of natural killer cells and cytotoxic T cells and the activation of type 1 helper T and type 17 helper T transcription factors were downregulated by risankizumab. Rates of adverse events were similar among patients receiving risankizumab and those taking placebo.
Further trials unwarranted
“The findings not only failed to show benefit for any outcome but also showed asthma worsening occurred earlier and more frequently in those treated with risankizumab versus placebo,” Dr. Brightling, professor in the department of respiratory sciences at University of Leicester, England, said in an interview. “This study does not support any further trials for anti-IL23 in asthma.” Dr. Brightling speculated on the cause of accelerated asthma worsening with risankizumab.
“We found that the gene expression of key molecules involved in our response to infection was decreased in airway samples in those treated with risankizumab versus placebo. It is possible that the increased asthma worsening following risankizumab was related to this suppression of antimicrobial immunity,” he said.
He noted that risankizumab did not affect type-2/eosinophilic inflammation, which is the target for current asthma biologics, or gene expression of T2 molecules. “That suggests that this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo,” he said.
Caution with investigating biologicals
Downstream biologic responses to risankizumab were detectable, Philip G. Bardin, PhD, and Paul S. Foster, DSc, observed in an accompanying editorial, but there was no discernible clinical benefit, implying attenuation of apposite pathways. Current understanding of the basic science relevant to asthma, they stated, offers clues to the failure of risankizumab to benefit these patients with severe asthma. Although targeting the interleukin-23 and Th17 axis with risankizumab can reduce development of pathogenic Th17 cells, interleukin-23 is not critical for the development of Th17 cells.
“In contrast to pathways operated by interleukin-5 and interleukin-4R alpha, interleukin-23 has only a limited auxiliary role in amplifying type 2 responses. It is possible that the trial conducted by Brightling and colleagues failed because signaling through alternative disease pathways nullified inhibition of inter-leukin-23,” the editorialists wrote.
Dr. Bardin and Dr. Foster further speculate that because interleukin-23 is vital for effective mucosal immunity, risankizumab may have conferred to patients a predisposition to more severe or more frequent virus-induced exacerbations. They stated that generally, however, the reasons for risankizumab’s poorer outcomes compared to placebo are unclear. “Overall, these findings support a cautious approach in future research investigating biologic therapies in asthma,” they concluded.
The clinical trial was sponsored and funded by BI/AbbVie.
A version of this article first appeared on Medscape.com.
Accused: Doc increases patient’s penis size with improper fillers; more
, as reported in NJ.com.
The physician, Muhammad A. Mirza, MD, is a board-certified internal medicine doctor and owner of Mirza Aesthetics, which has its main New Jersey office in Cedar Grove, a township in Essex County. The practice also leases space in New York, Pennsylvania, and Connecticut, where at press time Dr. Mirza was still licensed to practice medicine.
The acting New Jersey attorney general said that Dr. Mirza had deviated from the accepted standards of medical care in at least four key areas: he practiced in ways that put his patients in bodily danger; he lacked the formal training in and an adequate knowledge of aesthetic medicine; he practiced in office settings that inspectors found to be subpar; and he failed to safely store medical supplies or maintain proper medical records.
In one instance singled out by the attorney general’s office, Dr. Mirza used an injectable dermal filler to enhance a patient’s penis. As a result of that nonsurgical procedure, the patient needed to be rushed to a nearby hospital, where he underwent two emergency surgical interventions. Contacted by the emergency department doctor, Dr. Mirza allegedly failed to disclose the name of the filler he used, thereby complicating the patient’s recovery, according to the board complaint.
Dr. Mirza’s other alleged breaches of professional conduct include the following:
- Failure to wear a mask or surgical gloves during procedures
- Failure to keep electronic medical records of any kind
- Improper, off-label use of an injectable dermal filler in proximity to patients’ eyes
- Improper, off-label use of an injectable dermal filler for breast enhancement
- Use of a certain injectable dermal filler without first testing for skin allergies
In addition, site inspections of Dr. Mirza’s offices turned up substandard conditions. On April 23, 2021, in response to numerous patient complaints, the Enforcement Bureau of the Division of Consumer Affairs inspected Dr. Mirza’s Summit, N.J. office, one of several in the state.
Among other things, the inspection uncovered the following:
- The medical office was one large room. A curtain separated the reception area and the examination/treatment area, which consisted of only chairs and a fold-away table.
- “Duffle bags” were used to store injectable fillers. No medical storage refrigerators were observed.
- COVID-19 protocols were not followed. Inspectors could identify no barrier between receptionist and patients, no posted mask mandate, no social distancing policy, and no COVID-19 screening measures.
In addition to temporarily suspending Dr. Mirza’s license, the medical board has prohibited him from treating New Jersey patients in any of the out-of-state locations where he’s licensed to practice medicine.
Prosecutors have urged other patients who believe they’ve been injured by Mirza Aesthetics to file a complaint with the State Division of Consumer Affairs.
Dr. Mirza has agreed to the temporary suspension of his medical license, pending a hearing before an administrative law judge. In addition to facing civil penalties for each of the counts against him, he could be held responsible for paying investigative costs, attorney fees, trial costs, and other costs.
Doctor’s failure to diagnose results in mega award
In what is believed to be a record verdict in a wrongful death suit in Volusia County, Fla., a jury awarded $6.46 million to the family of a woman who died from an undiagnosed heart infection after being transferred from a local hospital, according to a report in The Daytona Beach News-Journal, among other news outlets.
In March 2016, Laura Staib went to what was then Florida Hospital DeLand — now AdventHealth DeLand — complaining of a variety of symptoms. There, she was examined by a doctor who was a member of a nearby cardiology group. His diagnosis: congestive heart failure, pneumonia, and sepsis. Transferred to a long-term care facility, Ms. Staib died 4 days later.
In their complaint against the cardiologist and his cardiology group, family members alleged that the doctor failed to identify Ms. Staib’s main problem: viral myocarditis.
“This was primarily a heart failure problem and a heart infection that was probably causing some problems in the lungs,” said the attorney representing the family. “A virus was attacking her heart, and they missed it,” he said. Claims against the hospital and other doctors were eventually resolved and dismissed.
The jury’s verdict will be appealed, said the attorney representing the cardiologist.
He argues that his client “did not cause that woman’s death. She died of an overwhelming lung infection...acute respiratory distress syndrome, caused by an overwhelming pneumonia that got worse after she was transferred to a facility where [my client] doesn’t practice.”
The bulk of the award will be in compensation for family members’ future pain and suffering and for other noneconomic damages.
Botched outpatient procedure leaves woman disfigured
In early September, a patient was allegedly administered the wrong drug during an outpatient procedure on her hand. She sued the Austin, Tex., hospital and surgical center where that procedure was performed, according to a story in Law/Street.
On January 9, 2020, Jessica Arguello went to HCA Healthcare’s South Austin Surgery Center to undergo a right-hand first metacarpophalangeal arthrodesis (fusion) and neuroma excision. In her suit against the hospital, Ms. Arguello claims that while her surgeon was preparing to close the incision after having irrigated the site, he called for a syringe containing an anesthetic. He was instead handed a syringe that contained formalin, the chemical used to preserve specimens for later review.
The mistake, Ms. Arguello claims, caused her to suffer massive chemical burns and necrosis of her flesh, which required four additional surgeries. In the end, she says, her right hand is disfigured and has limited mobility.
She adds that her injuries were preventable. Standard surgical procedure typically forbids chemicals such as formalin to be included among items on the prep tray. In addition to other compensation, she seeks damages for past and future medical expenses and past and future pain and suffering.
At press time, the defendants had not responded to Ms. Arguello’s complaint.
A version of this article first appeared on Medscape.com.
, as reported in NJ.com.
The physician, Muhammad A. Mirza, MD, is a board-certified internal medicine doctor and owner of Mirza Aesthetics, which has its main New Jersey office in Cedar Grove, a township in Essex County. The practice also leases space in New York, Pennsylvania, and Connecticut, where at press time Dr. Mirza was still licensed to practice medicine.
The acting New Jersey attorney general said that Dr. Mirza had deviated from the accepted standards of medical care in at least four key areas: he practiced in ways that put his patients in bodily danger; he lacked the formal training in and an adequate knowledge of aesthetic medicine; he practiced in office settings that inspectors found to be subpar; and he failed to safely store medical supplies or maintain proper medical records.
In one instance singled out by the attorney general’s office, Dr. Mirza used an injectable dermal filler to enhance a patient’s penis. As a result of that nonsurgical procedure, the patient needed to be rushed to a nearby hospital, where he underwent two emergency surgical interventions. Contacted by the emergency department doctor, Dr. Mirza allegedly failed to disclose the name of the filler he used, thereby complicating the patient’s recovery, according to the board complaint.
Dr. Mirza’s other alleged breaches of professional conduct include the following:
- Failure to wear a mask or surgical gloves during procedures
- Failure to keep electronic medical records of any kind
- Improper, off-label use of an injectable dermal filler in proximity to patients’ eyes
- Improper, off-label use of an injectable dermal filler for breast enhancement
- Use of a certain injectable dermal filler without first testing for skin allergies
In addition, site inspections of Dr. Mirza’s offices turned up substandard conditions. On April 23, 2021, in response to numerous patient complaints, the Enforcement Bureau of the Division of Consumer Affairs inspected Dr. Mirza’s Summit, N.J. office, one of several in the state.
Among other things, the inspection uncovered the following:
- The medical office was one large room. A curtain separated the reception area and the examination/treatment area, which consisted of only chairs and a fold-away table.
- “Duffle bags” were used to store injectable fillers. No medical storage refrigerators were observed.
- COVID-19 protocols were not followed. Inspectors could identify no barrier between receptionist and patients, no posted mask mandate, no social distancing policy, and no COVID-19 screening measures.
In addition to temporarily suspending Dr. Mirza’s license, the medical board has prohibited him from treating New Jersey patients in any of the out-of-state locations where he’s licensed to practice medicine.
Prosecutors have urged other patients who believe they’ve been injured by Mirza Aesthetics to file a complaint with the State Division of Consumer Affairs.
Dr. Mirza has agreed to the temporary suspension of his medical license, pending a hearing before an administrative law judge. In addition to facing civil penalties for each of the counts against him, he could be held responsible for paying investigative costs, attorney fees, trial costs, and other costs.
Doctor’s failure to diagnose results in mega award
In what is believed to be a record verdict in a wrongful death suit in Volusia County, Fla., a jury awarded $6.46 million to the family of a woman who died from an undiagnosed heart infection after being transferred from a local hospital, according to a report in The Daytona Beach News-Journal, among other news outlets.
In March 2016, Laura Staib went to what was then Florida Hospital DeLand — now AdventHealth DeLand — complaining of a variety of symptoms. There, she was examined by a doctor who was a member of a nearby cardiology group. His diagnosis: congestive heart failure, pneumonia, and sepsis. Transferred to a long-term care facility, Ms. Staib died 4 days later.
In their complaint against the cardiologist and his cardiology group, family members alleged that the doctor failed to identify Ms. Staib’s main problem: viral myocarditis.
“This was primarily a heart failure problem and a heart infection that was probably causing some problems in the lungs,” said the attorney representing the family. “A virus was attacking her heart, and they missed it,” he said. Claims against the hospital and other doctors were eventually resolved and dismissed.
The jury’s verdict will be appealed, said the attorney representing the cardiologist.
He argues that his client “did not cause that woman’s death. She died of an overwhelming lung infection...acute respiratory distress syndrome, caused by an overwhelming pneumonia that got worse after she was transferred to a facility where [my client] doesn’t practice.”
The bulk of the award will be in compensation for family members’ future pain and suffering and for other noneconomic damages.
Botched outpatient procedure leaves woman disfigured
In early September, a patient was allegedly administered the wrong drug during an outpatient procedure on her hand. She sued the Austin, Tex., hospital and surgical center where that procedure was performed, according to a story in Law/Street.
On January 9, 2020, Jessica Arguello went to HCA Healthcare’s South Austin Surgery Center to undergo a right-hand first metacarpophalangeal arthrodesis (fusion) and neuroma excision. In her suit against the hospital, Ms. Arguello claims that while her surgeon was preparing to close the incision after having irrigated the site, he called for a syringe containing an anesthetic. He was instead handed a syringe that contained formalin, the chemical used to preserve specimens for later review.
The mistake, Ms. Arguello claims, caused her to suffer massive chemical burns and necrosis of her flesh, which required four additional surgeries. In the end, she says, her right hand is disfigured and has limited mobility.
She adds that her injuries were preventable. Standard surgical procedure typically forbids chemicals such as formalin to be included among items on the prep tray. In addition to other compensation, she seeks damages for past and future medical expenses and past and future pain and suffering.
At press time, the defendants had not responded to Ms. Arguello’s complaint.
A version of this article first appeared on Medscape.com.
, as reported in NJ.com.
The physician, Muhammad A. Mirza, MD, is a board-certified internal medicine doctor and owner of Mirza Aesthetics, which has its main New Jersey office in Cedar Grove, a township in Essex County. The practice also leases space in New York, Pennsylvania, and Connecticut, where at press time Dr. Mirza was still licensed to practice medicine.
The acting New Jersey attorney general said that Dr. Mirza had deviated from the accepted standards of medical care in at least four key areas: he practiced in ways that put his patients in bodily danger; he lacked the formal training in and an adequate knowledge of aesthetic medicine; he practiced in office settings that inspectors found to be subpar; and he failed to safely store medical supplies or maintain proper medical records.
In one instance singled out by the attorney general’s office, Dr. Mirza used an injectable dermal filler to enhance a patient’s penis. As a result of that nonsurgical procedure, the patient needed to be rushed to a nearby hospital, where he underwent two emergency surgical interventions. Contacted by the emergency department doctor, Dr. Mirza allegedly failed to disclose the name of the filler he used, thereby complicating the patient’s recovery, according to the board complaint.
Dr. Mirza’s other alleged breaches of professional conduct include the following:
- Failure to wear a mask or surgical gloves during procedures
- Failure to keep electronic medical records of any kind
- Improper, off-label use of an injectable dermal filler in proximity to patients’ eyes
- Improper, off-label use of an injectable dermal filler for breast enhancement
- Use of a certain injectable dermal filler without first testing for skin allergies
In addition, site inspections of Dr. Mirza’s offices turned up substandard conditions. On April 23, 2021, in response to numerous patient complaints, the Enforcement Bureau of the Division of Consumer Affairs inspected Dr. Mirza’s Summit, N.J. office, one of several in the state.
Among other things, the inspection uncovered the following:
- The medical office was one large room. A curtain separated the reception area and the examination/treatment area, which consisted of only chairs and a fold-away table.
- “Duffle bags” were used to store injectable fillers. No medical storage refrigerators were observed.
- COVID-19 protocols were not followed. Inspectors could identify no barrier between receptionist and patients, no posted mask mandate, no social distancing policy, and no COVID-19 screening measures.
In addition to temporarily suspending Dr. Mirza’s license, the medical board has prohibited him from treating New Jersey patients in any of the out-of-state locations where he’s licensed to practice medicine.
Prosecutors have urged other patients who believe they’ve been injured by Mirza Aesthetics to file a complaint with the State Division of Consumer Affairs.
Dr. Mirza has agreed to the temporary suspension of his medical license, pending a hearing before an administrative law judge. In addition to facing civil penalties for each of the counts against him, he could be held responsible for paying investigative costs, attorney fees, trial costs, and other costs.
Doctor’s failure to diagnose results in mega award
In what is believed to be a record verdict in a wrongful death suit in Volusia County, Fla., a jury awarded $6.46 million to the family of a woman who died from an undiagnosed heart infection after being transferred from a local hospital, according to a report in The Daytona Beach News-Journal, among other news outlets.
In March 2016, Laura Staib went to what was then Florida Hospital DeLand — now AdventHealth DeLand — complaining of a variety of symptoms. There, she was examined by a doctor who was a member of a nearby cardiology group. His diagnosis: congestive heart failure, pneumonia, and sepsis. Transferred to a long-term care facility, Ms. Staib died 4 days later.
In their complaint against the cardiologist and his cardiology group, family members alleged that the doctor failed to identify Ms. Staib’s main problem: viral myocarditis.
“This was primarily a heart failure problem and a heart infection that was probably causing some problems in the lungs,” said the attorney representing the family. “A virus was attacking her heart, and they missed it,” he said. Claims against the hospital and other doctors were eventually resolved and dismissed.
The jury’s verdict will be appealed, said the attorney representing the cardiologist.
He argues that his client “did not cause that woman’s death. She died of an overwhelming lung infection...acute respiratory distress syndrome, caused by an overwhelming pneumonia that got worse after she was transferred to a facility where [my client] doesn’t practice.”
The bulk of the award will be in compensation for family members’ future pain and suffering and for other noneconomic damages.
Botched outpatient procedure leaves woman disfigured
In early September, a patient was allegedly administered the wrong drug during an outpatient procedure on her hand. She sued the Austin, Tex., hospital and surgical center where that procedure was performed, according to a story in Law/Street.
On January 9, 2020, Jessica Arguello went to HCA Healthcare’s South Austin Surgery Center to undergo a right-hand first metacarpophalangeal arthrodesis (fusion) and neuroma excision. In her suit against the hospital, Ms. Arguello claims that while her surgeon was preparing to close the incision after having irrigated the site, he called for a syringe containing an anesthetic. He was instead handed a syringe that contained formalin, the chemical used to preserve specimens for later review.
The mistake, Ms. Arguello claims, caused her to suffer massive chemical burns and necrosis of her flesh, which required four additional surgeries. In the end, she says, her right hand is disfigured and has limited mobility.
She adds that her injuries were preventable. Standard surgical procedure typically forbids chemicals such as formalin to be included among items on the prep tray. In addition to other compensation, she seeks damages for past and future medical expenses and past and future pain and suffering.
At press time, the defendants had not responded to Ms. Arguello’s complaint.
A version of this article first appeared on Medscape.com.
Free vitamin D no better at predicting death in men than standard testing
In the clinical assessment of vitamin D concentrations, free 25-hydroxyvitamin D shows little added benefit to the current standard of total 25(OH)D, with deficiencies in each associated with at least a twofold risk of all-cause mortality, new research shows.
“In this prospective, population-based study of middle-aged and older European men, total 25(OH)D levels below 20 mcg/L were independently associated with a twofold increased all-cause mortality,” the researchers reported.
“Lower concentrations of free 25(OH)D were also predictive of mortality, but did not provide any additional information,” they noted. “The data do not support routine measurement of free 25(OH)D or 1,25(OH)2D [1,25-dihydroxyvitamin D] over total 25(OH)D levels.”
Despite vitamin D deficiency being well established as playing a role in a wide range of adverse health effects, including cardiovascular disease and mortality, there has been a lack of consensus on the optimal concentration of total 25(OH)D, with studies showing inconsistent levels to define insufficiency and deficiency.
One aspect of the debate has focused on precisely how to measure the concentrations, with some evidence supporting the “free hormone hypothesis,” which suggests that free 25(OH)D could represent a better indicator than the standard total 25(OH)D of functional availability of vitamin D, and have stronger clinical utility.
To investigate both issues, Marian Dejaeger, MD, PhD, and colleagues evaluated prospective data on 1,915 men recruited from eight centers around Europe in the European Male Aging Study in a report published in the Journal of Clinical Endocrinology & Metabolism
The men, who were aged between 40 and 79 years, had a mean follow-up of 12.3 years; during that time, about a quarter (23.5%) of them died.
In addition to other factors, including being older, having a higher body mass index, and having at least two comorbidities, men who died had significantly lower levels of total 25(OH)D, total 1,25(OH)2D, free 25(OH)D, and free 1,25(OH)2D, as well as higher parathyroid hormone and creatinine values.
After adjustment for key confounders, including body mass index, smoking, alcohol consumption, kidney function, number of comorbidities at baseline and other factors, men with a total 25(OH)D below 20 mcg/L had a significantly increased risk of mortality, compared with those who had normal levels of vitamin D, defined as above 30 mcg/L (hazard ratio, 2.03; P < .001).
In terms of free 25(OH)D, the lowest three free 25(OH)D quintiles (under 4.43 ng/L) similarly had a significantly higher mortality risk, compared with the highest quintile (HR, 2.09; P < .01) after adjustment for the confounders.
Further observations of all quintiles of other measures of 1,25(OH)2D and vitamin D binding protein (DBP) showed no associations with mortality after adjusting for confounders.
Methods of measurement
An important caveat of the study is the type of method used to measure free 25(OH)D. The authors calculated free 25(OH)D using a formula, as opposed to the alternative of direct measurement with an enzyme-linked immunosorbent assay kit, and there can be important differences between the two approaches, said Daniel Bikle, MD, PhD, a professor of medicine and dermatology at the San Francisco Veterans Affairs Medical Center and University of California, San Francisco, in a comment on the research.
“The biggest problem is that calculating free 25(OH)D does not give an accurate estimate of the real free level, so making conclusions regarding its role in clinical situations is subject to error,” said Dr. Bikle, who recently authored a review of the free hormone hypothesis.
A calculation approach “depends heavily on the total 25(OH)D level, so in a population with reasonably normal DBP and albumin levels, the correlation with total 25(OH)D is very high, so I am not surprised by the results showing no additional value,” he said in an interview.
The authors addressed their use of the calculation over the direct measurement in the study, noting that there is a “high correlation between both methods.”
But they added that, “as no equilibrium analysis method is available for free 25(OH)D, nor for free 1,25(OH)2D, no method can be considered superior.”
Dr. Dejaeger, of the department of public health and primary care, Katholieke Universiteit Leuven (Belgium), added that she agreed that high or low DBP could potentially shift some correlations, but noted that other research has shown calculated and direct measures to match relatively well.
“So we partly agree [with Dr. Bikle] not being surprised that we did not find an added value because we also found little variation in DBP, but we are not convinced that a different measurement method could make the difference here.”
Another caveat of the study is that, despite half of the measurements being taken in the summer, more than 90% of subjects in the study’s cohort had vitamin D insufficiency, defined in the study as total 25(OH)D levels below 30 mcg/L, and as many as 70% had deficiency, with levels below 20 mcg/L.
Therefore, “as the number of participants with high levels of total 25(OH)D in our study is small, a true threshold concentration for optimal vitamin D status cannot be defined on basis of our data,” the authors noted.
Under current recommendations, the Endocrine Society indicates that concentrations below 30 mcg/L are insufficient, while other groups, including the Institute of Medicine, suggest concentrations of 20 mcg/L or above are adequate.
Free hormone hypothesis
Under the free hormone hypothesis, which is observed with thyroid hormones and sex steroids, the very small fraction of free hormones that are not bound to protein carriers can enter cells and help facilitate biologic activity.
The hypothesis of a role of free 25(OH)D in mortality was supported by a recent study, in which free 25(OH)D levels – but not total 25(OH)D levels, were found to be independently associated with an increased risk of all-cause and cardiovascular mortality among patients with coronary artery disease.
However, two other studies are more consistent with the new findings, including one study showing no added value of free 25(OH)D as a marker for bone mineral density in older women, and another study showing no value as a marker of metabolic variables in healthy children.
“Currently, there are no hard data to support routine measurements of free 25(OH)D or 1,25(OH)2D over total 25(OH)D, the current standard of assessing vitamin D status, as stated in guidelines from different scientific bodies,” Dr. Dejaeger said in an interview.
The study received support from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre. Dr. Dejaeger and Dr. Bikle had no disclosures to report.
In the clinical assessment of vitamin D concentrations, free 25-hydroxyvitamin D shows little added benefit to the current standard of total 25(OH)D, with deficiencies in each associated with at least a twofold risk of all-cause mortality, new research shows.
“In this prospective, population-based study of middle-aged and older European men, total 25(OH)D levels below 20 mcg/L were independently associated with a twofold increased all-cause mortality,” the researchers reported.
“Lower concentrations of free 25(OH)D were also predictive of mortality, but did not provide any additional information,” they noted. “The data do not support routine measurement of free 25(OH)D or 1,25(OH)2D [1,25-dihydroxyvitamin D] over total 25(OH)D levels.”
Despite vitamin D deficiency being well established as playing a role in a wide range of adverse health effects, including cardiovascular disease and mortality, there has been a lack of consensus on the optimal concentration of total 25(OH)D, with studies showing inconsistent levels to define insufficiency and deficiency.
One aspect of the debate has focused on precisely how to measure the concentrations, with some evidence supporting the “free hormone hypothesis,” which suggests that free 25(OH)D could represent a better indicator than the standard total 25(OH)D of functional availability of vitamin D, and have stronger clinical utility.
To investigate both issues, Marian Dejaeger, MD, PhD, and colleagues evaluated prospective data on 1,915 men recruited from eight centers around Europe in the European Male Aging Study in a report published in the Journal of Clinical Endocrinology & Metabolism
The men, who were aged between 40 and 79 years, had a mean follow-up of 12.3 years; during that time, about a quarter (23.5%) of them died.
In addition to other factors, including being older, having a higher body mass index, and having at least two comorbidities, men who died had significantly lower levels of total 25(OH)D, total 1,25(OH)2D, free 25(OH)D, and free 1,25(OH)2D, as well as higher parathyroid hormone and creatinine values.
After adjustment for key confounders, including body mass index, smoking, alcohol consumption, kidney function, number of comorbidities at baseline and other factors, men with a total 25(OH)D below 20 mcg/L had a significantly increased risk of mortality, compared with those who had normal levels of vitamin D, defined as above 30 mcg/L (hazard ratio, 2.03; P < .001).
In terms of free 25(OH)D, the lowest three free 25(OH)D quintiles (under 4.43 ng/L) similarly had a significantly higher mortality risk, compared with the highest quintile (HR, 2.09; P < .01) after adjustment for the confounders.
Further observations of all quintiles of other measures of 1,25(OH)2D and vitamin D binding protein (DBP) showed no associations with mortality after adjusting for confounders.
Methods of measurement
An important caveat of the study is the type of method used to measure free 25(OH)D. The authors calculated free 25(OH)D using a formula, as opposed to the alternative of direct measurement with an enzyme-linked immunosorbent assay kit, and there can be important differences between the two approaches, said Daniel Bikle, MD, PhD, a professor of medicine and dermatology at the San Francisco Veterans Affairs Medical Center and University of California, San Francisco, in a comment on the research.
“The biggest problem is that calculating free 25(OH)D does not give an accurate estimate of the real free level, so making conclusions regarding its role in clinical situations is subject to error,” said Dr. Bikle, who recently authored a review of the free hormone hypothesis.
A calculation approach “depends heavily on the total 25(OH)D level, so in a population with reasonably normal DBP and albumin levels, the correlation with total 25(OH)D is very high, so I am not surprised by the results showing no additional value,” he said in an interview.
The authors addressed their use of the calculation over the direct measurement in the study, noting that there is a “high correlation between both methods.”
But they added that, “as no equilibrium analysis method is available for free 25(OH)D, nor for free 1,25(OH)2D, no method can be considered superior.”
Dr. Dejaeger, of the department of public health and primary care, Katholieke Universiteit Leuven (Belgium), added that she agreed that high or low DBP could potentially shift some correlations, but noted that other research has shown calculated and direct measures to match relatively well.
“So we partly agree [with Dr. Bikle] not being surprised that we did not find an added value because we also found little variation in DBP, but we are not convinced that a different measurement method could make the difference here.”
Another caveat of the study is that, despite half of the measurements being taken in the summer, more than 90% of subjects in the study’s cohort had vitamin D insufficiency, defined in the study as total 25(OH)D levels below 30 mcg/L, and as many as 70% had deficiency, with levels below 20 mcg/L.
Therefore, “as the number of participants with high levels of total 25(OH)D in our study is small, a true threshold concentration for optimal vitamin D status cannot be defined on basis of our data,” the authors noted.
Under current recommendations, the Endocrine Society indicates that concentrations below 30 mcg/L are insufficient, while other groups, including the Institute of Medicine, suggest concentrations of 20 mcg/L or above are adequate.
Free hormone hypothesis
Under the free hormone hypothesis, which is observed with thyroid hormones and sex steroids, the very small fraction of free hormones that are not bound to protein carriers can enter cells and help facilitate biologic activity.
The hypothesis of a role of free 25(OH)D in mortality was supported by a recent study, in which free 25(OH)D levels – but not total 25(OH)D levels, were found to be independently associated with an increased risk of all-cause and cardiovascular mortality among patients with coronary artery disease.
However, two other studies are more consistent with the new findings, including one study showing no added value of free 25(OH)D as a marker for bone mineral density in older women, and another study showing no value as a marker of metabolic variables in healthy children.
“Currently, there are no hard data to support routine measurements of free 25(OH)D or 1,25(OH)2D over total 25(OH)D, the current standard of assessing vitamin D status, as stated in guidelines from different scientific bodies,” Dr. Dejaeger said in an interview.
The study received support from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre. Dr. Dejaeger and Dr. Bikle had no disclosures to report.
In the clinical assessment of vitamin D concentrations, free 25-hydroxyvitamin D shows little added benefit to the current standard of total 25(OH)D, with deficiencies in each associated with at least a twofold risk of all-cause mortality, new research shows.
“In this prospective, population-based study of middle-aged and older European men, total 25(OH)D levels below 20 mcg/L were independently associated with a twofold increased all-cause mortality,” the researchers reported.
“Lower concentrations of free 25(OH)D were also predictive of mortality, but did not provide any additional information,” they noted. “The data do not support routine measurement of free 25(OH)D or 1,25(OH)2D [1,25-dihydroxyvitamin D] over total 25(OH)D levels.”
Despite vitamin D deficiency being well established as playing a role in a wide range of adverse health effects, including cardiovascular disease and mortality, there has been a lack of consensus on the optimal concentration of total 25(OH)D, with studies showing inconsistent levels to define insufficiency and deficiency.
One aspect of the debate has focused on precisely how to measure the concentrations, with some evidence supporting the “free hormone hypothesis,” which suggests that free 25(OH)D could represent a better indicator than the standard total 25(OH)D of functional availability of vitamin D, and have stronger clinical utility.
To investigate both issues, Marian Dejaeger, MD, PhD, and colleagues evaluated prospective data on 1,915 men recruited from eight centers around Europe in the European Male Aging Study in a report published in the Journal of Clinical Endocrinology & Metabolism
The men, who were aged between 40 and 79 years, had a mean follow-up of 12.3 years; during that time, about a quarter (23.5%) of them died.
In addition to other factors, including being older, having a higher body mass index, and having at least two comorbidities, men who died had significantly lower levels of total 25(OH)D, total 1,25(OH)2D, free 25(OH)D, and free 1,25(OH)2D, as well as higher parathyroid hormone and creatinine values.
After adjustment for key confounders, including body mass index, smoking, alcohol consumption, kidney function, number of comorbidities at baseline and other factors, men with a total 25(OH)D below 20 mcg/L had a significantly increased risk of mortality, compared with those who had normal levels of vitamin D, defined as above 30 mcg/L (hazard ratio, 2.03; P < .001).
In terms of free 25(OH)D, the lowest three free 25(OH)D quintiles (under 4.43 ng/L) similarly had a significantly higher mortality risk, compared with the highest quintile (HR, 2.09; P < .01) after adjustment for the confounders.
Further observations of all quintiles of other measures of 1,25(OH)2D and vitamin D binding protein (DBP) showed no associations with mortality after adjusting for confounders.
Methods of measurement
An important caveat of the study is the type of method used to measure free 25(OH)D. The authors calculated free 25(OH)D using a formula, as opposed to the alternative of direct measurement with an enzyme-linked immunosorbent assay kit, and there can be important differences between the two approaches, said Daniel Bikle, MD, PhD, a professor of medicine and dermatology at the San Francisco Veterans Affairs Medical Center and University of California, San Francisco, in a comment on the research.
“The biggest problem is that calculating free 25(OH)D does not give an accurate estimate of the real free level, so making conclusions regarding its role in clinical situations is subject to error,” said Dr. Bikle, who recently authored a review of the free hormone hypothesis.
A calculation approach “depends heavily on the total 25(OH)D level, so in a population with reasonably normal DBP and albumin levels, the correlation with total 25(OH)D is very high, so I am not surprised by the results showing no additional value,” he said in an interview.
The authors addressed their use of the calculation over the direct measurement in the study, noting that there is a “high correlation between both methods.”
But they added that, “as no equilibrium analysis method is available for free 25(OH)D, nor for free 1,25(OH)2D, no method can be considered superior.”
Dr. Dejaeger, of the department of public health and primary care, Katholieke Universiteit Leuven (Belgium), added that she agreed that high or low DBP could potentially shift some correlations, but noted that other research has shown calculated and direct measures to match relatively well.
“So we partly agree [with Dr. Bikle] not being surprised that we did not find an added value because we also found little variation in DBP, but we are not convinced that a different measurement method could make the difference here.”
Another caveat of the study is that, despite half of the measurements being taken in the summer, more than 90% of subjects in the study’s cohort had vitamin D insufficiency, defined in the study as total 25(OH)D levels below 30 mcg/L, and as many as 70% had deficiency, with levels below 20 mcg/L.
Therefore, “as the number of participants with high levels of total 25(OH)D in our study is small, a true threshold concentration for optimal vitamin D status cannot be defined on basis of our data,” the authors noted.
Under current recommendations, the Endocrine Society indicates that concentrations below 30 mcg/L are insufficient, while other groups, including the Institute of Medicine, suggest concentrations of 20 mcg/L or above are adequate.
Free hormone hypothesis
Under the free hormone hypothesis, which is observed with thyroid hormones and sex steroids, the very small fraction of free hormones that are not bound to protein carriers can enter cells and help facilitate biologic activity.
The hypothesis of a role of free 25(OH)D in mortality was supported by a recent study, in which free 25(OH)D levels – but not total 25(OH)D levels, were found to be independently associated with an increased risk of all-cause and cardiovascular mortality among patients with coronary artery disease.
However, two other studies are more consistent with the new findings, including one study showing no added value of free 25(OH)D as a marker for bone mineral density in older women, and another study showing no value as a marker of metabolic variables in healthy children.
“Currently, there are no hard data to support routine measurements of free 25(OH)D or 1,25(OH)2D over total 25(OH)D, the current standard of assessing vitamin D status, as stated in guidelines from different scientific bodies,” Dr. Dejaeger said in an interview.
The study received support from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre. Dr. Dejaeger and Dr. Bikle had no disclosures to report.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
German society for internal medicine reappraises its Nazi history
. The decision was made after the DGIM reappraised its own history during the Nazi period.
On the DGIM - Commemoration and Remembrance website, created in 2020, members who suffered under the Nazi regime are commemorated and those who committed crimes and caused suffering are called out.
The reappraisal began in 2012, when the DGIM commissioned two historians — Hans-Georg Hofer, PhD, from the University of Münster, and Ralf Forsbach, PhD, from the Institute for Ethics, History and Theory of Medicine at the University of Münster — to research the history of the society and its members during the periods of the National Socialism dictatorship and the young Federal Republic.
“Reappraising our own history, even at this late stage, is important and the right thing to do, although of course it cannot in any way make up for the suffering caused by individual DGIM members during that time,” Georg Ertl, MD, secretary general of the DGIM, states in a press release.
It is important, however, that the Society takes appropriate action in response to the historians’ findings, he adds.
The DGIM has done just that by retrospectively withdrawing the honorary membership status of five of its former members: Alfred Schittenhelm, Alfred Schwenkenbecher, Hans Dietlen, Siegfried Koller, and Georg Schaltenbrand.
“Out of opportunism or on the basis of Nazi beliefs, they intentionally harmed colleagues, other members of our Society, or simply other people on the basis of their ethnicity. Therefore, the DGIM can no longer accept them as honorary members,” said Markus M. Lerch, MD, chair of the DGIM and medical director of the Ludwig Maximilian University of Munich.
The board has also distanced itself from two other honorary members: Gustav von Bergmann and Felix Lommel. “More research is needed and we cannot currently make a responsible decision on withdrawal of honorary membership,” Dr. Lerch explained.
Early results from the historical reappraisal were presented to the public in 2015 at an exhibition held during the 121st DGIM Congress in Mannheim. The Society concurrently underwent a process of public self-reflection, stating that it was ashamed of having allowed 70 years to pass before it objectively examined its actions under National Socialism and acknowledged its responsibility.
The exhibition used photos, documents, and explanatory texts to show the actions, or lack of action, taken by some Society members during the Nazi regime. For example, it showed how then DGIM chair Alfred Schittenhelm — whose honorary membership has since been withdrawn — put the Society on the track to National Socialism. It also shone light on the role played by internists who consulted with the Wehrmacht in the treatment of Soviet prisoners of war and others, and on criminal experiments conducted on humans.
The exhibition also highlighted Jewish doctors who were persecuted and expelled, such as Leopold Lichtwitz, MD, who lost his position as clinic director in Berlin in 1933 and was forced to resign his chairmanship of the Society. And it presented portraits of members who loudly objected to and even actively resisted the regime, such as Wolfgang Seitz, MD, who became director of the Medical Outpatient Clinic at the University of Munich and deputy of the state parliament of the Social Democratic Party of Germany (SPD) in Bavaria after the war.
The historians focused on the years after 1945, because “1945 was no zero hour,” said Dr. Forsbach. Some culpable doctors continued to practice or became honorary DGIM members, he explained. The DGIM’s attitude toward history was characterized by suppression, denial, silence, and attempts at justification, consistent with the postwar attitude in the Federal Republic of Germany and in the medical profession as a whole.
After 1945
Behavior before 1945 is not the only source of shame. Crimes committed by doctors were never really confronted until the late 1970s, Jörg-Dietrich Hoppe, MD, former president of the German Medical Association, explained to ZEIT, a German newspaper, in 2011.
The psychoanalyst Alexander Mitscherlich, MD, and Fred Mielke were official observers from the German Commission of Physicians at the Nuremberg Doctors’ Trial who were made painfully aware that National Socialism was by no means over when the regime came to an end. They were both reviled as traitors to their country and for fouling their own nest, and, according to Mitscherlich, the behavior of the “authorities” bordered on character assassination.
As late as 1973, a renowned internist threatened that German internists would leave the room locked at the upcoming DGIM Congress if — as had been planned by congress chair Herbert Begemann — Mitscherlich gave a talk on this subject, journalist and doctor Renate Jäckle reported in her book on doctors and politics.
Even toward the end of the 1980s, Karsten Vilmar, MD, then president of the German Medical Association, reacted in an insensitive and defensive manner — during an interview — to an article in the Lancet, written by the Mainz pediatrician Hartmut M. Hanauske-Abel, MD, on the role of the German medical profession in the Third Reich and the suppression that followed after 1945.
A group of 400 doctors, at most, were culpable, and coming to terms with the past should not defame doctors collectively, Dr. Vilmar said in a statement chillingly reminiscent of declarations made by the Wehrmacht, which described itself as mainly “clean.”
Of course, the end of the Nazi regime was not the end of all barbarity, not even in Europe. “Violence will be something we have to confront in our future lives, too. Belief in the healing powers of civilization is nothing but a fairytale,” Berlin historian Jörg Barberowski wrote in a 2012 essay.
Nevertheless, as Michael Hallek, MD, from the University Hospital of Cologne, said, it is important to keep memory alive.
A version of this article first appeared on Medscape.com.
. The decision was made after the DGIM reappraised its own history during the Nazi period.
On the DGIM - Commemoration and Remembrance website, created in 2020, members who suffered under the Nazi regime are commemorated and those who committed crimes and caused suffering are called out.
The reappraisal began in 2012, when the DGIM commissioned two historians — Hans-Georg Hofer, PhD, from the University of Münster, and Ralf Forsbach, PhD, from the Institute for Ethics, History and Theory of Medicine at the University of Münster — to research the history of the society and its members during the periods of the National Socialism dictatorship and the young Federal Republic.
“Reappraising our own history, even at this late stage, is important and the right thing to do, although of course it cannot in any way make up for the suffering caused by individual DGIM members during that time,” Georg Ertl, MD, secretary general of the DGIM, states in a press release.
It is important, however, that the Society takes appropriate action in response to the historians’ findings, he adds.
The DGIM has done just that by retrospectively withdrawing the honorary membership status of five of its former members: Alfred Schittenhelm, Alfred Schwenkenbecher, Hans Dietlen, Siegfried Koller, and Georg Schaltenbrand.
“Out of opportunism or on the basis of Nazi beliefs, they intentionally harmed colleagues, other members of our Society, or simply other people on the basis of their ethnicity. Therefore, the DGIM can no longer accept them as honorary members,” said Markus M. Lerch, MD, chair of the DGIM and medical director of the Ludwig Maximilian University of Munich.
The board has also distanced itself from two other honorary members: Gustav von Bergmann and Felix Lommel. “More research is needed and we cannot currently make a responsible decision on withdrawal of honorary membership,” Dr. Lerch explained.
Early results from the historical reappraisal were presented to the public in 2015 at an exhibition held during the 121st DGIM Congress in Mannheim. The Society concurrently underwent a process of public self-reflection, stating that it was ashamed of having allowed 70 years to pass before it objectively examined its actions under National Socialism and acknowledged its responsibility.
The exhibition used photos, documents, and explanatory texts to show the actions, or lack of action, taken by some Society members during the Nazi regime. For example, it showed how then DGIM chair Alfred Schittenhelm — whose honorary membership has since been withdrawn — put the Society on the track to National Socialism. It also shone light on the role played by internists who consulted with the Wehrmacht in the treatment of Soviet prisoners of war and others, and on criminal experiments conducted on humans.
The exhibition also highlighted Jewish doctors who were persecuted and expelled, such as Leopold Lichtwitz, MD, who lost his position as clinic director in Berlin in 1933 and was forced to resign his chairmanship of the Society. And it presented portraits of members who loudly objected to and even actively resisted the regime, such as Wolfgang Seitz, MD, who became director of the Medical Outpatient Clinic at the University of Munich and deputy of the state parliament of the Social Democratic Party of Germany (SPD) in Bavaria after the war.
The historians focused on the years after 1945, because “1945 was no zero hour,” said Dr. Forsbach. Some culpable doctors continued to practice or became honorary DGIM members, he explained. The DGIM’s attitude toward history was characterized by suppression, denial, silence, and attempts at justification, consistent with the postwar attitude in the Federal Republic of Germany and in the medical profession as a whole.
After 1945
Behavior before 1945 is not the only source of shame. Crimes committed by doctors were never really confronted until the late 1970s, Jörg-Dietrich Hoppe, MD, former president of the German Medical Association, explained to ZEIT, a German newspaper, in 2011.
The psychoanalyst Alexander Mitscherlich, MD, and Fred Mielke were official observers from the German Commission of Physicians at the Nuremberg Doctors’ Trial who were made painfully aware that National Socialism was by no means over when the regime came to an end. They were both reviled as traitors to their country and for fouling their own nest, and, according to Mitscherlich, the behavior of the “authorities” bordered on character assassination.
As late as 1973, a renowned internist threatened that German internists would leave the room locked at the upcoming DGIM Congress if — as had been planned by congress chair Herbert Begemann — Mitscherlich gave a talk on this subject, journalist and doctor Renate Jäckle reported in her book on doctors and politics.
Even toward the end of the 1980s, Karsten Vilmar, MD, then president of the German Medical Association, reacted in an insensitive and defensive manner — during an interview — to an article in the Lancet, written by the Mainz pediatrician Hartmut M. Hanauske-Abel, MD, on the role of the German medical profession in the Third Reich and the suppression that followed after 1945.
A group of 400 doctors, at most, were culpable, and coming to terms with the past should not defame doctors collectively, Dr. Vilmar said in a statement chillingly reminiscent of declarations made by the Wehrmacht, which described itself as mainly “clean.”
Of course, the end of the Nazi regime was not the end of all barbarity, not even in Europe. “Violence will be something we have to confront in our future lives, too. Belief in the healing powers of civilization is nothing but a fairytale,” Berlin historian Jörg Barberowski wrote in a 2012 essay.
Nevertheless, as Michael Hallek, MD, from the University Hospital of Cologne, said, it is important to keep memory alive.
A version of this article first appeared on Medscape.com.
. The decision was made after the DGIM reappraised its own history during the Nazi period.
On the DGIM - Commemoration and Remembrance website, created in 2020, members who suffered under the Nazi regime are commemorated and those who committed crimes and caused suffering are called out.
The reappraisal began in 2012, when the DGIM commissioned two historians — Hans-Georg Hofer, PhD, from the University of Münster, and Ralf Forsbach, PhD, from the Institute for Ethics, History and Theory of Medicine at the University of Münster — to research the history of the society and its members during the periods of the National Socialism dictatorship and the young Federal Republic.
“Reappraising our own history, even at this late stage, is important and the right thing to do, although of course it cannot in any way make up for the suffering caused by individual DGIM members during that time,” Georg Ertl, MD, secretary general of the DGIM, states in a press release.
It is important, however, that the Society takes appropriate action in response to the historians’ findings, he adds.
The DGIM has done just that by retrospectively withdrawing the honorary membership status of five of its former members: Alfred Schittenhelm, Alfred Schwenkenbecher, Hans Dietlen, Siegfried Koller, and Georg Schaltenbrand.
“Out of opportunism or on the basis of Nazi beliefs, they intentionally harmed colleagues, other members of our Society, or simply other people on the basis of their ethnicity. Therefore, the DGIM can no longer accept them as honorary members,” said Markus M. Lerch, MD, chair of the DGIM and medical director of the Ludwig Maximilian University of Munich.
The board has also distanced itself from two other honorary members: Gustav von Bergmann and Felix Lommel. “More research is needed and we cannot currently make a responsible decision on withdrawal of honorary membership,” Dr. Lerch explained.
Early results from the historical reappraisal were presented to the public in 2015 at an exhibition held during the 121st DGIM Congress in Mannheim. The Society concurrently underwent a process of public self-reflection, stating that it was ashamed of having allowed 70 years to pass before it objectively examined its actions under National Socialism and acknowledged its responsibility.
The exhibition used photos, documents, and explanatory texts to show the actions, or lack of action, taken by some Society members during the Nazi regime. For example, it showed how then DGIM chair Alfred Schittenhelm — whose honorary membership has since been withdrawn — put the Society on the track to National Socialism. It also shone light on the role played by internists who consulted with the Wehrmacht in the treatment of Soviet prisoners of war and others, and on criminal experiments conducted on humans.
The exhibition also highlighted Jewish doctors who were persecuted and expelled, such as Leopold Lichtwitz, MD, who lost his position as clinic director in Berlin in 1933 and was forced to resign his chairmanship of the Society. And it presented portraits of members who loudly objected to and even actively resisted the regime, such as Wolfgang Seitz, MD, who became director of the Medical Outpatient Clinic at the University of Munich and deputy of the state parliament of the Social Democratic Party of Germany (SPD) in Bavaria after the war.
The historians focused on the years after 1945, because “1945 was no zero hour,” said Dr. Forsbach. Some culpable doctors continued to practice or became honorary DGIM members, he explained. The DGIM’s attitude toward history was characterized by suppression, denial, silence, and attempts at justification, consistent with the postwar attitude in the Federal Republic of Germany and in the medical profession as a whole.
After 1945
Behavior before 1945 is not the only source of shame. Crimes committed by doctors were never really confronted until the late 1970s, Jörg-Dietrich Hoppe, MD, former president of the German Medical Association, explained to ZEIT, a German newspaper, in 2011.
The psychoanalyst Alexander Mitscherlich, MD, and Fred Mielke were official observers from the German Commission of Physicians at the Nuremberg Doctors’ Trial who were made painfully aware that National Socialism was by no means over when the regime came to an end. They were both reviled as traitors to their country and for fouling their own nest, and, according to Mitscherlich, the behavior of the “authorities” bordered on character assassination.
As late as 1973, a renowned internist threatened that German internists would leave the room locked at the upcoming DGIM Congress if — as had been planned by congress chair Herbert Begemann — Mitscherlich gave a talk on this subject, journalist and doctor Renate Jäckle reported in her book on doctors and politics.
Even toward the end of the 1980s, Karsten Vilmar, MD, then president of the German Medical Association, reacted in an insensitive and defensive manner — during an interview — to an article in the Lancet, written by the Mainz pediatrician Hartmut M. Hanauske-Abel, MD, on the role of the German medical profession in the Third Reich and the suppression that followed after 1945.
A group of 400 doctors, at most, were culpable, and coming to terms with the past should not defame doctors collectively, Dr. Vilmar said in a statement chillingly reminiscent of declarations made by the Wehrmacht, which described itself as mainly “clean.”
Of course, the end of the Nazi regime was not the end of all barbarity, not even in Europe. “Violence will be something we have to confront in our future lives, too. Belief in the healing powers of civilization is nothing but a fairytale,” Berlin historian Jörg Barberowski wrote in a 2012 essay.
Nevertheless, as Michael Hallek, MD, from the University Hospital of Cologne, said, it is important to keep memory alive.
A version of this article first appeared on Medscape.com.
Hot temperatures in outdoor lockboxes increase sample errors
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to results from a recent study published in the American Journal of Clinical Pathology.
“Our findings indicate that samples (centrifuged or not centrifuged) were impacted by extreme summer temperatures when stored for short periods of time inside commonly used steel lockboxes,” Joseph R. Wiencek, PhD, medical director of clinical chemistry, Vanderbilt University School of Medicine Core Laboratory in Nashville, said in an interview.
Dr. Wiencek and colleagues picked two dates during the summer of 2019 in a mid-Atlantic state to place two courier lockboxes (LabLocker-KF300) outside in hot temperatures (32º C) starting at 11 a.m., with one lockbox containing two 24-oz cold packs (Nordic NI24) and the other containing no cold packs. The researchers monitored the temperatures of each lockbox over the course of 4 hours.
Overall, eight participants had seven samples in lithium heparin drawn for two studies evaluating centrifuged or not centrifuged samples. In the first study, four participants had seven samples drawn, with one centrifuged sample serving as a control for each patient. The other six samples were wrapped in paper towels, placed in resealable plastic bags, and distributed evenly in the warm and cold lockboxes. The samples did not directly touch the cold packs in the cold lockbox. At 1 hour, 2 hours, and 4 hours, a participant’s sample was removed from each lockbox and centrifuged.
In the second study, another four participants had seven samples drawn. As in the first study, all samples were centrifuged and placed in the lockboxes. For both studies, when samples were centrifuged, plasma from samples was left on the gel barrier when analyzed for concentrations of C-reactive protein, a comprehensive metabolic panel, lactate dehydrogenase (LDH), a lipid panel, magnesium, and phosphorus (Abbott Architect c16000).
In the study of uncentrifuged samples, Dr. Wiencek and colleagues found that when the temperature outside ranged from 28.2º to 44.0º C (mean 40.4º C), the temperature of the cold lockbox was between 16.5º to 22.3º C (mean 22.3º C). The temperature ranged between 34.4º to 46.9º C (mean 42.6º C) in the warm lockbox. For centrifuged samples, the cold lockbox temperature was between 12.2º to 23.0º C (mean 18.0º C) and the warm lockbox was between 25. to 40.8º C (mean 35.2º C) when the outdoor temperature ranged from 27.2º to 46.3º C (mean 37.9º C).
The researchers also calculated the significant change limit (SCL) for each analyte in each sample, finding that aspartate aminotransferase, glucose, LDH, and potassium significantly exceeded the SCL in both the centrifuged and uncentrifuged samples, with the greatest changes seen at the 4-hour timepoint for samples in the warm lockbox (P < .05 for all).
Lockbox instructions are “consistently inconsistent”
In viewing instructions for lockboxes across institutions, Dr. Wiencek said the “outdoor courier lockbox instructions among private, academic and reference laboratories were consistently inconsistent.” For example, no laboratories cited time restrictions for samples in lockboxes, and their descriptions on the number of cold packs a laboratory should use and where the lockbox should be placed varied. The inconsistencies “highlighted the emergent need for standardization and guidance documents for institutions to implement,” Dr. Wiencek said.
One unanswered question is how widespread the problem is. It is unclear how many outdoor courier lockboxes are currently in use in the United States or globally; however, experts agreed it was a common occurrence, with some of the largest laboratory service providers offering outdoor courier lockboxes to their clients.
“Courier lockboxes are everywhere. All you need to do is walk around your clinics that are at your hospitals or clinics located around your grocery store to find them,” Dr. Wiencek said. “Some hang on doors, while others can be found on the ground in direct sunlight on a hot summer day.”
What’s more, institutions may not realize how leaving samples outdoors for extended periods can affect results. “Care teams are commonly unaware that samples placed in these poorly designed lockboxes can experience extreme summer or winter temperatures that may lead to incorrect results,” Dr. Wiencek said. “Healthcare providers need to understand the hidden dangers courier lockboxes have on the quality of their patient’s test results.”
Amy L. Pyle-Eilola, PhD, clinical chemistry director at Nationwide Children’s Hospital in Columbus, Ohio, said a major strength of the study by Dr. Wiencek and colleagues “is just that it was done at all.”
“I appreciate the real-world nature of this study and that it provides a snapshot of what conditions are really like in a lockbox in the summer,” she said in an interview.
In the clinical lab, receiving samples that had been sitting in a courier lockbox “is not uncommon,” Dr. Pyle-Eilola said.
“When I have encountered these situations, I have struggled to decide if it is still appropriate to run the tests. I always look to the medical literature for assistance with these situations, but there has been a paucity of information available on the impact of lockbox storage,” she explained.
The study by Dr. Wiencek and colleagues “provides some much-needed evidence for what is acceptable for lockbox storage conditions,” she said.
Areas of future research
Rodney E. Rohde, PhD, university distinguished chair and professor of the Clinical Laboratory Science (CLS) Program at Texas State University in San Marcos, said in an interview that the study “does a nice job of looking at multiple analytes and controlling for several variables,” but the sample size is small and the results may be difficult to generalize.
Dr. Pyle-Eilola highlighted another limitation — “a common shortcoming of these kinds of studies” — in the use of healthy donors for patient samples, which narrows the range of assay results.
“It is possible that more significant variation in results may be observed in additional analytes if the samples had higher concentrations of those analytes,” she said. “Moreover, this is clinically relevant as the samples stored in such lockboxes are not always from healthy individuals and have abnormal concentrations of analytes.”
Mario Plebani, MD, professor of clinical biochemistry and clinical molecular biology and chief of the department of laboratory medicine at University Hospital of Padova in Padova, Italy, agreed with that assessment.
“[T]he risks for errors and patient safety are higher for values near to the upper or lower reference value, and in general for samples collected in patients with particular diseases and clinical conditions,” he said in an interview.
“This paper deserves a commenting editorial to better highlight the urgent need for further studies on the same issue and in general on the risk in the pre-pre-analytical phase, including sample storage and transportation,” he noted.
Another area of future research is studying patient samples exposed to hotter or colder temperatures in outdoor courier lockboxes outside the mid-Atlantic area. “Here in Texas, temperatures can reach extreme heat levels,” Dr. Rohde said, who added that use of outdoor lockboxes is “very common in my region.”
Dr. Wiencek disclosed he has been a consultant on this research topic for Roche Diagnostics and received an honorarium for speaking on the subject from the American Association for Clinical Chemistry and American Society of Clinical Pathology. The other authors have no relevant conflict of interest. Dr. Pyle-Eilola, Dr. Rohde, and Dr. Plebani have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Vitamin D status may play a pivotal role in colon cancer prevention
This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.
Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.
“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.
Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
The evidence is in, but it’s incomplete
In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.
A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.
In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.
The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D3 supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.
Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.
The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.
“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”
In animal models, vitamin D3 is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.
Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.
“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D3 can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
The hazards of a vitamin D deficiency
A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.
Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.
The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D3) at 800-1,000 IU daily from dietary and supplemental sources.
Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.
This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.
Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.
“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.
Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
The evidence is in, but it’s incomplete
In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.
A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.
In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.
The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D3 supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.
Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.
The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.
“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”
In animal models, vitamin D3 is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.
Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.
“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D3 can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
The hazards of a vitamin D deficiency
A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.
Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.
The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D3) at 800-1,000 IU daily from dietary and supplemental sources.
Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.
This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.
Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.
“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.
Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
The evidence is in, but it’s incomplete
In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.
A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.
In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.
The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D3 supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.
Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.
The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.
“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”
In animal models, vitamin D3 is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.
Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.
“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D3 can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
The hazards of a vitamin D deficiency
A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.
Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.
The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D3) at 800-1,000 IU daily from dietary and supplemental sources.
Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.
FROM GASTROENTEROLOGY
Top case
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:
Vikrant Parihar, MD, wrote the following in “COVID-19 and UC”:
A 43-year-old man with an index presentation of distal colitis (Montreal E2) (Mayo endoscopic score 2-3) was discharged home on tapering doses of oral steroids. He was being worked up to commence anti-TNF likely initially as combo therapy. Fully vaccinated against COVID – had both doses of vaccine way back in May. Attended a match and looks to have got mild symptoms and on testing turned out to be COVID+. Rx himself by self-quarantine.
What would be the optimal strategy?
1. Stop steroids completely and immediately given the adverse signal in registry data?
2. When can anti-TNF’s be safely started?
3. How to manage him in the interim?
See how AGA members responded and join the discussion: https://community.gastro.org/posts/25172.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:
Vikrant Parihar, MD, wrote the following in “COVID-19 and UC”:
A 43-year-old man with an index presentation of distal colitis (Montreal E2) (Mayo endoscopic score 2-3) was discharged home on tapering doses of oral steroids. He was being worked up to commence anti-TNF likely initially as combo therapy. Fully vaccinated against COVID – had both doses of vaccine way back in May. Attended a match and looks to have got mild symptoms and on testing turned out to be COVID+. Rx himself by self-quarantine.
What would be the optimal strategy?
1. Stop steroids completely and immediately given the adverse signal in registry data?
2. When can anti-TNF’s be safely started?
3. How to manage him in the interim?
See how AGA members responded and join the discussion: https://community.gastro.org/posts/25172.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:
Vikrant Parihar, MD, wrote the following in “COVID-19 and UC”:
A 43-year-old man with an index presentation of distal colitis (Montreal E2) (Mayo endoscopic score 2-3) was discharged home on tapering doses of oral steroids. He was being worked up to commence anti-TNF likely initially as combo therapy. Fully vaccinated against COVID – had both doses of vaccine way back in May. Attended a match and looks to have got mild symptoms and on testing turned out to be COVID+. Rx himself by self-quarantine.
What would be the optimal strategy?
1. Stop steroids completely and immediately given the adverse signal in registry data?
2. When can anti-TNF’s be safely started?
3. How to manage him in the interim?
See how AGA members responded and join the discussion: https://community.gastro.org/posts/25172.
Judge dismisses Lyme disease lawsuit against IDSA, doctors, but the ordeal has left its scars
Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.
“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”
It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.
But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.
“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”
So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.
“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”
Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.
“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”
But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
‘Preposterous’ accusations
The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.
What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.
“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”
Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.
Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.
“The assertions were just preposterous,” Dr. McQuillen said.
In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.
Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.
“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”
Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.
“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.
Choosing to fight
Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.
“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”
Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.
“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”
IDSA could have chosen to settle the lawsuit, as the insurance companies did.
“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.
Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.
“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”
Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.
“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”
If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.
“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”
To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.
“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.
“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.
“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”
At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.
“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”
A version of this article first appeared on Medscape.com.
Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.
“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”
It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.
But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.
“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”
So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.
“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”
Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.
“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”
But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
‘Preposterous’ accusations
The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.
What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.
“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”
Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.
Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.
“The assertions were just preposterous,” Dr. McQuillen said.
In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.
Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.
“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”
Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.
“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.
Choosing to fight
Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.
“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”
Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.
“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”
IDSA could have chosen to settle the lawsuit, as the insurance companies did.
“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.
Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.
“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”
Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.
“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”
If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.
“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”
To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.
“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.
“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.
“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”
At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.
“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”
A version of this article first appeared on Medscape.com.
Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.
“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”
It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.
But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.
“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”
So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.
“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”
Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.
“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”
But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
‘Preposterous’ accusations
The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.
What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.
“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”
Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.
Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.
“The assertions were just preposterous,” Dr. McQuillen said.
In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.
Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.
“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”
Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.
“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.
Choosing to fight
Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.
“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”
Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.
“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”
IDSA could have chosen to settle the lawsuit, as the insurance companies did.
“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.
Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.
“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”
Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.
“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”
If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.
“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”
To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.
“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.
“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.
“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”
At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.
“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”
A version of this article first appeared on Medscape.com.
Rachel Levine: Making History Every Step of the Way
“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.
In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.
All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.
In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.
One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.
In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”
Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.
“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.
When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.
Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.
She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”
At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.
In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.
Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.
When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”
Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”
In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”
Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.
“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”
HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”
Levine told the Senate committee, “There is still so much more to do.”
“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.
In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.
All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.
In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.
One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.
In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”
Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.
“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.
When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.
Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.
She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”
At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.
In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.
Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.
When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”
Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”
In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”
Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.
“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”
HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”
Levine told the Senate committee, “There is still so much more to do.”
“We each come to public service in our own unique way,” ADM Rachel Levine, MD, Assistant Secretary for Health at the US Department of Health and Human Services (HHS), told the Senate Health, Education, Labor and Pensions Committee at her confirmation hearing in February 2021.
In her case, unique and history-making. Levine was confirmed on Tuesday as the first-ever openly transgender—and firstwoman—four-star admiral in the history of the US Public Health Service Commissioned Corps. She is also the first openly transgender four-star officer and the first openly transgender person to be confirmed by the Senate. In fact, she is the nation’s highest-ranking openly transgender official—the first such across any of the eight uniformed services.
All those firsts aside, in her confirmation hearing remarks, ADM. Levine said, “At its core, my career has been about helping people live healthy lives.” She began her career at Mt. Sinai Medical Center in New York, in pediatric and adolescent medicine, focusing on mental and physical health. Moving to the Penn State College of Medicine, ADM Levine was a professor of pediatrics and psychiatry and vice-chair for clinical affairs for the Department of Pediatrics. At Penn State, she initiated the Division of Adolescent Medicine for the care of complex teens with medical and psychological problems. As chief of the Division of Adolescent Medicine and Eating Disorders at Penn State Hershey Medical Center, she also founded an eating disorders program, offering multidisciplinary treatment for children, adolescents, and adults.
In 2015, Pennsylvania Governor Tom Wolf nominated ADM Levine to be Physician General of the Commonwealth of Pennsylvania and she was confirmed unanimously by the state senate. In 2018, she was named Pennsylvania’s Secretary of Health. In these roles, she tackled the state’s massive opioid misuse and overdose crisis. She focused on opioid stewardship, developed continuing medical education programs, and established prescribing guidelines and a “robust” prescription drug monitoring program. She traveled extensively throughout small communities, doing public events with local officials and residents to talk about opioid abuse. The efforts began, slowly, to pay off. In 2015, 3,383 people died of drug overdose in Pennsylvania, a 23% increase from 2014. By 2018, 65% of drug overdose deaths involved opioids, but the total number of deaths fell to 2,866.
One of her most significant accomplishments as Physician General, Levine said, was to issue the first-ever statewide standing order for distribution of the anti-overdose drug naloxone, allowing law enforcement to carry the drug and Pennsylvania citizens to buy itover the counter. According to the Pennsylvania Opioid Data Dashboard, between January 1, 2018, and October 9, 2021, 62,954 doses of naloxone were administered by EMS.
In another of Levine’s projects, the Pennsylvania Rural Health Model, the goal was to move rural hospitals from fee-for-service models to global budget payments, which she said, “aligned incentives for providers to deliver value-based care and for rural hospitals to transform their care to better meet community health needs.”
Working in tandem with HHS, Levine’s teams also set up a maternal mortality review committee “to better understand and respond to the causes of maternal deaths,” and worked to improve childhood immunization rates.
“Of course, our focus changed dramatically last year,” Levine said, “and COVID-19 became my most urgent and primary focus.” She concentrated on three key priorities: containment with expansion of testing and contact tracing; mitigation with masks and distancing; and medical countermeasures, including monoclonal antibodies and vaccines. To carry out the strategies, she oversaw a health equity task force, which included community stakeholders such as the Black Coalition Against COVID-19, the Latino Connection, and a faith-based program that allowed people to get tested at their places of worship.
When lesbian, gay, bisexual, transgender, queer; lesbian, gay, bisexual, transgender, queer (LGBTQ+) advocates charged that states were not collecting data early in the pandemic on sexual orientation or gender identity, in another historic move, Levine announced in March 2020 that Pennsylvania would begin collecting demographic data on the coronavirus, making it the first state in the country to do so.
Levine has garnered praise from many sources. “This is a proud moment for us,” HHS Secretary Xavier Becerra said in a statement, calling her a “cherished and critical partner in our work to build a healthier America.” Alphonso David, then president of the Human Rights Campaign, said in a statement that Levine’s nomination to be the HHS Assistant Secretary for Health represented “real change” in the government’s approach to the coronavirus and LGBTQ+ health issues. Levine “led Pennsylvania’s public health response to the COVID-19 pandemic superbly,” he said.
She has also triggered a significant amount of outrage in conservative quarters. She was routinely castigated for her early actions in the pandemic. Writing for The American Spectator in May 2020, Paul Kengor, a former UPMC researcher, said UPMC’s overall handling of the virus was “impressive and inspired confidence.” However, tracking the data on fatalities, he said, he found the disproportionate number of deaths in nursing homes “alarming and strange.” Citing an investigative article in the Bucks County Courier Times, he blamed Pennsylvania officials—including Levine—for guidelines that directed licensed long-term care facilities to continue admitting new patients, including those discharged from hospitals back to nursing homes. However, Kengor claimed, the “partisan press” would protect Wolf and Levine: “Levine is a liberal darling as the nation’s first (and arguably highest-ranking) transgender public official.”
At the February 2021 federal confirmation hearing, Levine was pressed on data discrepancies in Pennsylvania’s public reports on nursing home coronavirus deaths and cases. Sen. Susan Collins (R-ME) cited Spotlight PA reporting that found weekly reports released by the state health department were consistently missing data for more than 100 of the 693 nursing homes. Levine, in response, pointed to lags in the state’s electronic death reporting system and to slow uploads. Pennsylvania health officials also referred to a state law that prohibits the release of disease records by state or local authorities.
In a June 2020 opinion article, Levine wrote that the Pennsylvania Health Department had followed Centers for Disease Control and Prevention (CDC) guidance, including limiting outside people from entering long-term care facilities. The Pennsylvania Health Department also sent thousands of shipments of personal protective equipment and conducted virtual inspections, including on-site inspections as warranted.
Despite those efforts, Levine said, “staff members who have dedicated their lives to caring for these vulnerable Pennsylvanians unknowingly contracted COVID-19 in their communities and carried it into these facilities.” She pointed out that residents who returned from hospitals had been isolated if they contracted COVID-19. Patients returning to nursing homes did not introduce COVID-19, Levine said, “because it was there that they first came into contact with the virus.” Moreover, those patients were isolated, just as they had been before they required hospital-level care, she added.
When a long-term care facility reports a case of COVID-19, Levine noted, the Pennsylvania Health Department considers it an outbreak and offers a variety of resources to the facility, including mitigation measures and the services of an infection control consultant, or even deploying the Pennsylvania National Guard to assist with staffing. Pennsylvania cannot force facilities to accept these services, she pointed out, but some refuse out of fear of receiving citations. “[O]ur top priority,” Levine said, “is halting COVID-19, not issuing citations.”
Her decisions on health restrictions and closures to combat the pandemic created controversy in the state, but much of the criticism also took aim at Levine identifying openly as transgender. Her selection as the first openly transgender official to be confirmed by the Senate has been targeted by conservative groups as a political gesture by President Biden. Tom Fitton, president of the conservative legal group Judicial Watch, posted on Facebook: “Biden gang playing quota politics with public health service.”
In her remarks to the Senate committee, however, Levine calmly noted that her appointment by Gov. Wolf was confirmed unanimously and that she was approved twice more on a bipartisan basis to be Secretary of Health. She met with nearly all of the senators personally. Her confirmation by the senate Republicans was particularly meaningful, she told NBC Out. “[They] judged me strictly on my professional qualifications.”
Social media has made much of Levine’s transgender identification, both pro and con. The Twitterverse, predictably, is packed with anti-Levine and anti-LGBTQ+ rants. But Levine’s rise has energized the LGBTQ+ community, who hail it as a breakthrough. Scout, the single-named executive director of the National LGBT Cancer Network, said, “The fact that she is trans is an inspiration for the many of us who have never had a role model this senior before.” Levine herself is determined to be a “beacon” in representing the LGBTQ+ community in her latest role at the corps: “Diversity makes us stronger,” she said.
“What people don’t understand, they fear,” Levine, who is a frequent public speaker, has said. “The more we can educate people and show that we’re productive members of the community—with families, lives, careers—that helps people understand us better.” That includes education of medical professionals. “We need to do a better job educating medical students about LGBT issues and transgender medicine,” she told NBC Out. She may need to start with the members of Congress. At Levine’s confirmation hearing to serve as Assistant Secretary for Health, Sen. Rand Paul, for instance, compared transgender surgery to “genital mutilation.”
HHS Secretary Becerra called Levine’s appointment as the first openly transgender four-star officer “a giant step forward toward equality as a nation.” US Surgeon General VADM Vivek Murthy, MD, MBA, said her appointment represents “an important step towards a more inclusive future and her service will undoubtedly advance the US Public Health Service Commissioned Corps’ mission to protect, promote, and advance the health and safety of our nation.”
Levine told the Senate committee, “There is still so much more to do.”