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The multiple meanings of sex
Knowing the sex of a developing fetus is a common question many expectant parents ask at their prenatal appointments. While the sex of a fetus has minimal clinical significance to obstetrician/gynecologists, technology has made ascertaining the answer to this question much more accessible.
In addition to detecting certain genetic abnormalities, both noninvasive prenatal testing (NIPT) and preimplantation genetic testing (PGT) can discern the chromosomal sex of a fetus prior to birth. At the 20-week anatomy scan, the ultrasonographer can detect the presence of external genitalia to determine the sex. In fact, when a baby is first born, obstetrician/gynecologists are consistently asked “do I have a boy or a girl?” Assigning the sex of a newborn is one of the many tasks we complete in the delivery room. However, some of you reading this article would disagree.
“You cannot assign sex at birth.” “Sex is fixed, you cannot change biology.” These are examples of statements that frequent the comments section of my medical articles and plague professionals who treat gender diverse patients. I would argue, as would many biologists, scientists, and physicians, that these statements oversimplify biologic reality.
The term “sex” has multiple meanings: It can allude to the act of reproduction itself, but in the context of sexual determination and sexual differentiation, it can refer to the biologic and structural composition of a developing human. Within this paradigm, there exist three definitions for sex: chromosomal, gonadal, and phenotypic.
Chromosomal sex refers to the genetic makeup of a human, typically XX or XY chromosomes. There are also variations within this seemingly binary system. Embryos can have an extra sex chromosome, as seen in Klinefelter syndrome, which is characterized by XXY karyotype. Embryos can also be devoid of a sex chromosome, as observed in Turner’s syndrome, which is characterized by an XO karyotype. These variations can impact fertility and expression of secondary sexual characteristics as the type of sex chromosomes present results in primary sex determination, or the development of gonads.
Most often, individuals with a chromosomal makeup of XX are considered female and will subsequently develop ovaries that produce oocytes (eggs). Individuals with XY chromosomes are deemed male and will go on to develop testes, which are responsible for spermatogenesis (sperm production).
Gonadal sex is the presence of either testes or ovaries. The primary function of testes is to produce sperm for reproduction and to secrete testosterone, the primary male sex hormone. Similarly, ovaries produce oocytes and secrete estrogen as the primary female sex hormone. Gonads can be surgically removed either via orchiectomy (the removal of testes), or oophorectomy (the removal of ovaries) for a variety of reasons. There is no current medical technology that can replace the function of these structures, although patients can be placed on hormone replacement to counter the negative physiologic consequences resulting from their removal.
Secondary sex determination, or sexual differentiation, is the development of external genitalia and internal genital tracts because of the hormones produced from the gonads. At puberty, further differentiation occurs with the development of pubic and axillary hair and breast growth. This process determines phenotypic sex – the visible distinction between male and female.
When opponents of gender affirming care state that individuals cannot change sex, are they correct or false? The answer to this question is entirely dependent on which definition of sex they are using. Chromosomal? Gonadal? Phenotypic? It is an immutable fact that humans cannot change chromosomal sex. No one in the transgender community, either provider or patient, would dispute this. However, we can remove gonadal structures and alter phenotypic sex.
In fact, many cisgender individuals also revise their phenotypic sex when they undergo augmentation mammaplasty, penile enlargement, or vulvoplasty procedures for the exact same reason.
Circling back to the debate about whether we can “assign sex at birth,” it all depends on what definition of sex you are referencing. At birth, obstetrician/gynecologists most often look at the phenotypic sex and make assumptions about the genetic and gonadal sex based on the secondary sexual characteristics. So yes, we can, and we do assign sex at birth. However, in the case of intersex individuals, these physical characteristics may not align with their gonadal and chromosomal composition.
In the case of an infant that has a known XY karyotype prior to birth but a female phenotype at birth (as seen in a condition called complete androgen insensitivity syndrome), what sex should be assigned to that baby? Should the infant be raised male or female? A lot of unintended but significant harm has resulted from providers and parents trying to answer that very question. The mistreatment of intersex patients through forced and coercive medical and surgical treatments, often in infancy, should serve as a dark reminder that sex and gender are not as biologically binary as we would like to believe.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no relevant disclosures.
References
Moore KL and Persaud TVN. The urogenital system. In: Before we are born: essentials of embryology and birth defects. 7th ed. Philadelphia: Saunders Elsevier;2008:163-89.
Standring S. Development of the urogenital system. In: Gray’s Anatomy, 42nd ed. Philadelphia: Elsevier;2021:341-64.
Escobar O et al. Pediatric endocrinology. In: Zitelli BJ, ed. Zitelli and Davis’ atlas of pediatric physical diagnosis 8th edition. Philadelphia: Elsevier;2023:342-81.
Knowing the sex of a developing fetus is a common question many expectant parents ask at their prenatal appointments. While the sex of a fetus has minimal clinical significance to obstetrician/gynecologists, technology has made ascertaining the answer to this question much more accessible.
In addition to detecting certain genetic abnormalities, both noninvasive prenatal testing (NIPT) and preimplantation genetic testing (PGT) can discern the chromosomal sex of a fetus prior to birth. At the 20-week anatomy scan, the ultrasonographer can detect the presence of external genitalia to determine the sex. In fact, when a baby is first born, obstetrician/gynecologists are consistently asked “do I have a boy or a girl?” Assigning the sex of a newborn is one of the many tasks we complete in the delivery room. However, some of you reading this article would disagree.
“You cannot assign sex at birth.” “Sex is fixed, you cannot change biology.” These are examples of statements that frequent the comments section of my medical articles and plague professionals who treat gender diverse patients. I would argue, as would many biologists, scientists, and physicians, that these statements oversimplify biologic reality.
The term “sex” has multiple meanings: It can allude to the act of reproduction itself, but in the context of sexual determination and sexual differentiation, it can refer to the biologic and structural composition of a developing human. Within this paradigm, there exist three definitions for sex: chromosomal, gonadal, and phenotypic.
Chromosomal sex refers to the genetic makeup of a human, typically XX or XY chromosomes. There are also variations within this seemingly binary system. Embryos can have an extra sex chromosome, as seen in Klinefelter syndrome, which is characterized by XXY karyotype. Embryos can also be devoid of a sex chromosome, as observed in Turner’s syndrome, which is characterized by an XO karyotype. These variations can impact fertility and expression of secondary sexual characteristics as the type of sex chromosomes present results in primary sex determination, or the development of gonads.
Most often, individuals with a chromosomal makeup of XX are considered female and will subsequently develop ovaries that produce oocytes (eggs). Individuals with XY chromosomes are deemed male and will go on to develop testes, which are responsible for spermatogenesis (sperm production).
Gonadal sex is the presence of either testes or ovaries. The primary function of testes is to produce sperm for reproduction and to secrete testosterone, the primary male sex hormone. Similarly, ovaries produce oocytes and secrete estrogen as the primary female sex hormone. Gonads can be surgically removed either via orchiectomy (the removal of testes), or oophorectomy (the removal of ovaries) for a variety of reasons. There is no current medical technology that can replace the function of these structures, although patients can be placed on hormone replacement to counter the negative physiologic consequences resulting from their removal.
Secondary sex determination, or sexual differentiation, is the development of external genitalia and internal genital tracts because of the hormones produced from the gonads. At puberty, further differentiation occurs with the development of pubic and axillary hair and breast growth. This process determines phenotypic sex – the visible distinction between male and female.
When opponents of gender affirming care state that individuals cannot change sex, are they correct or false? The answer to this question is entirely dependent on which definition of sex they are using. Chromosomal? Gonadal? Phenotypic? It is an immutable fact that humans cannot change chromosomal sex. No one in the transgender community, either provider or patient, would dispute this. However, we can remove gonadal structures and alter phenotypic sex.
In fact, many cisgender individuals also revise their phenotypic sex when they undergo augmentation mammaplasty, penile enlargement, or vulvoplasty procedures for the exact same reason.
Circling back to the debate about whether we can “assign sex at birth,” it all depends on what definition of sex you are referencing. At birth, obstetrician/gynecologists most often look at the phenotypic sex and make assumptions about the genetic and gonadal sex based on the secondary sexual characteristics. So yes, we can, and we do assign sex at birth. However, in the case of intersex individuals, these physical characteristics may not align with their gonadal and chromosomal composition.
In the case of an infant that has a known XY karyotype prior to birth but a female phenotype at birth (as seen in a condition called complete androgen insensitivity syndrome), what sex should be assigned to that baby? Should the infant be raised male or female? A lot of unintended but significant harm has resulted from providers and parents trying to answer that very question. The mistreatment of intersex patients through forced and coercive medical and surgical treatments, often in infancy, should serve as a dark reminder that sex and gender are not as biologically binary as we would like to believe.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no relevant disclosures.
References
Moore KL and Persaud TVN. The urogenital system. In: Before we are born: essentials of embryology and birth defects. 7th ed. Philadelphia: Saunders Elsevier;2008:163-89.
Standring S. Development of the urogenital system. In: Gray’s Anatomy, 42nd ed. Philadelphia: Elsevier;2021:341-64.
Escobar O et al. Pediatric endocrinology. In: Zitelli BJ, ed. Zitelli and Davis’ atlas of pediatric physical diagnosis 8th edition. Philadelphia: Elsevier;2023:342-81.
Knowing the sex of a developing fetus is a common question many expectant parents ask at their prenatal appointments. While the sex of a fetus has minimal clinical significance to obstetrician/gynecologists, technology has made ascertaining the answer to this question much more accessible.
In addition to detecting certain genetic abnormalities, both noninvasive prenatal testing (NIPT) and preimplantation genetic testing (PGT) can discern the chromosomal sex of a fetus prior to birth. At the 20-week anatomy scan, the ultrasonographer can detect the presence of external genitalia to determine the sex. In fact, when a baby is first born, obstetrician/gynecologists are consistently asked “do I have a boy or a girl?” Assigning the sex of a newborn is one of the many tasks we complete in the delivery room. However, some of you reading this article would disagree.
“You cannot assign sex at birth.” “Sex is fixed, you cannot change biology.” These are examples of statements that frequent the comments section of my medical articles and plague professionals who treat gender diverse patients. I would argue, as would many biologists, scientists, and physicians, that these statements oversimplify biologic reality.
The term “sex” has multiple meanings: It can allude to the act of reproduction itself, but in the context of sexual determination and sexual differentiation, it can refer to the biologic and structural composition of a developing human. Within this paradigm, there exist three definitions for sex: chromosomal, gonadal, and phenotypic.
Chromosomal sex refers to the genetic makeup of a human, typically XX or XY chromosomes. There are also variations within this seemingly binary system. Embryos can have an extra sex chromosome, as seen in Klinefelter syndrome, which is characterized by XXY karyotype. Embryos can also be devoid of a sex chromosome, as observed in Turner’s syndrome, which is characterized by an XO karyotype. These variations can impact fertility and expression of secondary sexual characteristics as the type of sex chromosomes present results in primary sex determination, or the development of gonads.
Most often, individuals with a chromosomal makeup of XX are considered female and will subsequently develop ovaries that produce oocytes (eggs). Individuals with XY chromosomes are deemed male and will go on to develop testes, which are responsible for spermatogenesis (sperm production).
Gonadal sex is the presence of either testes or ovaries. The primary function of testes is to produce sperm for reproduction and to secrete testosterone, the primary male sex hormone. Similarly, ovaries produce oocytes and secrete estrogen as the primary female sex hormone. Gonads can be surgically removed either via orchiectomy (the removal of testes), or oophorectomy (the removal of ovaries) for a variety of reasons. There is no current medical technology that can replace the function of these structures, although patients can be placed on hormone replacement to counter the negative physiologic consequences resulting from their removal.
Secondary sex determination, or sexual differentiation, is the development of external genitalia and internal genital tracts because of the hormones produced from the gonads. At puberty, further differentiation occurs with the development of pubic and axillary hair and breast growth. This process determines phenotypic sex – the visible distinction between male and female.
When opponents of gender affirming care state that individuals cannot change sex, are they correct or false? The answer to this question is entirely dependent on which definition of sex they are using. Chromosomal? Gonadal? Phenotypic? It is an immutable fact that humans cannot change chromosomal sex. No one in the transgender community, either provider or patient, would dispute this. However, we can remove gonadal structures and alter phenotypic sex.
In fact, many cisgender individuals also revise their phenotypic sex when they undergo augmentation mammaplasty, penile enlargement, or vulvoplasty procedures for the exact same reason.
Circling back to the debate about whether we can “assign sex at birth,” it all depends on what definition of sex you are referencing. At birth, obstetrician/gynecologists most often look at the phenotypic sex and make assumptions about the genetic and gonadal sex based on the secondary sexual characteristics. So yes, we can, and we do assign sex at birth. However, in the case of intersex individuals, these physical characteristics may not align with their gonadal and chromosomal composition.
In the case of an infant that has a known XY karyotype prior to birth but a female phenotype at birth (as seen in a condition called complete androgen insensitivity syndrome), what sex should be assigned to that baby? Should the infant be raised male or female? A lot of unintended but significant harm has resulted from providers and parents trying to answer that very question. The mistreatment of intersex patients through forced and coercive medical and surgical treatments, often in infancy, should serve as a dark reminder that sex and gender are not as biologically binary as we would like to believe.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa. She has no relevant disclosures.
References
Moore KL and Persaud TVN. The urogenital system. In: Before we are born: essentials of embryology and birth defects. 7th ed. Philadelphia: Saunders Elsevier;2008:163-89.
Standring S. Development of the urogenital system. In: Gray’s Anatomy, 42nd ed. Philadelphia: Elsevier;2021:341-64.
Escobar O et al. Pediatric endocrinology. In: Zitelli BJ, ed. Zitelli and Davis’ atlas of pediatric physical diagnosis 8th edition. Philadelphia: Elsevier;2023:342-81.
Hypertensive disorders of pregnancy and high stroke risk in Black women
I’d like to talk with you about a recent report from the large-scale Black Women’s Health Study, published in the new journal NEJM Evidence.
This study looked at the association between hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, and the risk for stroke over the next 20 (median, 22) years. Previous studies have linked hypertensive disorders of pregnancy with an increased risk for stroke. However, most of these studies have been done in White women of European ancestry, and evidence in Black women has been very limited, despite a disproportionately high risk of having a hypertensive disorder of pregnancy and also of stroke.
– overall, a 66% increased risk, an 80% increased risk with gestational hypertension, and about a 50% increased risk with preeclampsia.
We know that pregnancy itself can lead to some remodeling of the vascular system, but we don’t know whether a direct causal relationship exists between preeclampsia or gestational hypertension and subsequent stroke. Another potential explanation is that these complications of pregnancy serve as a window into a woman’s future cardiometabolic health and a marker of her cardiovascular risk.
Regardless, the clinical implications are the same. First, we would want to prevent these complications of pregnancy whenever possible. Some women will be candidates for the use of aspirin if they are at high risk for preeclampsia, and certainly for monitoring blood pressure very closely during pregnancy. It will also be important to maintain blood pressure control in the postpartum period and during the subsequent years of adulthood to minimize risk for stroke, because hypertension is such a powerful risk factor for stroke.
It will also be tremendously important to intensify lifestyle modifications such as increasing physical activity and having a heart-healthy diet. These complications of pregnancy have also been linked in other studies to an increased risk for subsequent coronary heart disease events and heart failure.
This transcript has been edited for clarity.
Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, and chief of the division of preventive medicine, Brigham and Women’s Hospital, both in Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
I’d like to talk with you about a recent report from the large-scale Black Women’s Health Study, published in the new journal NEJM Evidence.
This study looked at the association between hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, and the risk for stroke over the next 20 (median, 22) years. Previous studies have linked hypertensive disorders of pregnancy with an increased risk for stroke. However, most of these studies have been done in White women of European ancestry, and evidence in Black women has been very limited, despite a disproportionately high risk of having a hypertensive disorder of pregnancy and also of stroke.
– overall, a 66% increased risk, an 80% increased risk with gestational hypertension, and about a 50% increased risk with preeclampsia.
We know that pregnancy itself can lead to some remodeling of the vascular system, but we don’t know whether a direct causal relationship exists between preeclampsia or gestational hypertension and subsequent stroke. Another potential explanation is that these complications of pregnancy serve as a window into a woman’s future cardiometabolic health and a marker of her cardiovascular risk.
Regardless, the clinical implications are the same. First, we would want to prevent these complications of pregnancy whenever possible. Some women will be candidates for the use of aspirin if they are at high risk for preeclampsia, and certainly for monitoring blood pressure very closely during pregnancy. It will also be important to maintain blood pressure control in the postpartum period and during the subsequent years of adulthood to minimize risk for stroke, because hypertension is such a powerful risk factor for stroke.
It will also be tremendously important to intensify lifestyle modifications such as increasing physical activity and having a heart-healthy diet. These complications of pregnancy have also been linked in other studies to an increased risk for subsequent coronary heart disease events and heart failure.
This transcript has been edited for clarity.
Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, and chief of the division of preventive medicine, Brigham and Women’s Hospital, both in Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
I’d like to talk with you about a recent report from the large-scale Black Women’s Health Study, published in the new journal NEJM Evidence.
This study looked at the association between hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, and the risk for stroke over the next 20 (median, 22) years. Previous studies have linked hypertensive disorders of pregnancy with an increased risk for stroke. However, most of these studies have been done in White women of European ancestry, and evidence in Black women has been very limited, despite a disproportionately high risk of having a hypertensive disorder of pregnancy and also of stroke.
– overall, a 66% increased risk, an 80% increased risk with gestational hypertension, and about a 50% increased risk with preeclampsia.
We know that pregnancy itself can lead to some remodeling of the vascular system, but we don’t know whether a direct causal relationship exists between preeclampsia or gestational hypertension and subsequent stroke. Another potential explanation is that these complications of pregnancy serve as a window into a woman’s future cardiometabolic health and a marker of her cardiovascular risk.
Regardless, the clinical implications are the same. First, we would want to prevent these complications of pregnancy whenever possible. Some women will be candidates for the use of aspirin if they are at high risk for preeclampsia, and certainly for monitoring blood pressure very closely during pregnancy. It will also be important to maintain blood pressure control in the postpartum period and during the subsequent years of adulthood to minimize risk for stroke, because hypertension is such a powerful risk factor for stroke.
It will also be tremendously important to intensify lifestyle modifications such as increasing physical activity and having a heart-healthy diet. These complications of pregnancy have also been linked in other studies to an increased risk for subsequent coronary heart disease events and heart failure.
This transcript has been edited for clarity.
Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, and chief of the division of preventive medicine, Brigham and Women’s Hospital, both in Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
How to think about second-line therapy in NSCLC
This transcript has been edited for clarity.
I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.
I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.
The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.
For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.
With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.
Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.
For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.
Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.
I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m2 or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.
I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.
Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.
I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.
The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.
For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.
With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.
Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.
For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.
Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.
I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m2 or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.
I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.
Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.
I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.
The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.
For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.
With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.
Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.
For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.
Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.
I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m2 or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.
I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.
Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article first appeared on Medscape.com.
Perinatal depression rarely stands alone
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Breastfeeding and colorectal cancer
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
GI symptoms during menopause deserve attention
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome back to another GI Common Concerns.
Today, I want to highlight some information about menopause.
Approximately 1.5 million women in the United States per year enter into menopause. Hysterectomy is also one of the most common surgeries for women worldwide, with an estimated 20%-40% undergoing this procedure by the age of 60.
Therefore, whether it’s because of biologic onset with age or surgical induction, menopause is a very common condition, and it’s important that we understand its symptoms and the latest information around it.
Impact on GI motility
One of the clearest functional symptoms to be aware of with menopause relates to alterations in hormonal balance. This has an impact on gastrointestinal (GI) motility by increasing abdominal muscle stimulation related to different patterns of secretion and can result in a number of symptomatic changes.
One such change that can occur is food intolerance. It is believed that menopause-associated food intolerance has multiple possible causes and may be related more to alterations to the microbiome, which can be contributed to by diet, activity, sleep cycle, and other factors.
When food intolerances are triggered in the perimenopausal or menopausal patient, it may lead you to recommend the well-established FODMAP diet, which is known to reduce symptoms. But the answer for every patient is not simply placing them on a FODMAP diet and telling them they have irritable bowel syndrome.
Other approaches can be considered for addressing food intolerance in these patients. The data are quite strong that adjunctive use of a dietitian is tremendously helpful in this particular population.
When it comes to menopausal patients, however, we need to consider other changes in their activity or adverse contributors to their mental health, such as stress or anxiety. These all contribute to more of a multifactorial composite in this population, for which irritable bowel syndrome serves as a similar example.
This means that we may need to expand our horizons rather than to focus on solely on antispasmodic or diet-related interventions.
Instead, we can start to consider more of a multidimensional treatment approach consisting of education, relaxation, cognitive-behavioral therapy, and physical activity. Certainly, there are now behavioral interventions using Internet-based digital formats to increase the acceptability and sustainability among patients.
Choosing such a multidisciplinary approach can be quite helpful.
The metabolic consequences of altering hormonal balance
Recent data from a rat model study investigated the metabolic impact of changing hormonal balance.
Investigators looked at ovariectomized rats and found that there was a biologic change in the diversity of the general GI biome. There were also noteworthy associations with weight fluctuations and dramatic changes in the spatial memory and cognitive performance characteristics of these rats, which was subsequently improved by supplemental estrogen.
This indicates that we may be able to remediate these effects with the similar use of supplemental hormone replacement treatments.
Another recent study looked at nonalcoholic fatty liver disease, which is very common in the general population and has a > 20% worldwide prevalence in postmenopausal women. Albeit small in numbers, this was a very interesting study.
Investigators looked at the delivery method for menopausal hormone therapy, which was transdermal for 75 patients and oral for 293 patients. Then, they looked at ultrasound definition of nonalcoholic fatty liver disease after 1 year as the endpoint. They found an approximate 7% reduction in the patients who received the transdermal administration compared with a 4% increase in the patients who received it orally.
Again, we have to remember this is a relatively small study, but the results indicate that the route of estrogen administration may be an important consideration in nonalcoholic fatty liver disease.
Sleep disturbances: fragmentation, duration, and quality
Sleep is something that’s near and dear to my heart and is the focus of a lot of our research.
Sleep disturbances are really part and parcel of menopause and are observed with hormonal imbalances and temperature intolerances. Disturbances such as sleep fragmentation, shorter sleep duration, and poorer sleep quality have a dramatic effect not only on the biome but also on sensory thresholds.
Therefore, as we start to look at mitigating strategies here, we need to focus on sleep and ask the right questions.
In my own practice, I try not to just ask, “How did you sleep last night?” That’s because sleep can be somewhat amnestic. You may have a cognitive awakening or a noncognitive awakening but still have experienced fragmentation.
As a result, my focus is on next-day function. I ask my patients, “When you get up in the morning, are you refreshed? Do you have the ability to perform daytime activities? Do you experience early fatigue or cognitive changes that occur?”
These questions can provide good insights into the sleep efficiency of the previous night.
The effect of the microbiome on osteoporosis
One final topic I found very interesting pertains to the effects of menopause on osteoporosis.
We certainly know that postmenopausal women have a very high prevalence of osteopenia, and that osteoporosis is a progression of that, as well as that increased bone-related disease affects fractures and related morbidity and mortality.
However, there’s accumulating evidence on the osteoporotic effects of biomarker changes in menopause, which shows that the biome regulates the pathophysiologic process of at least a large degree of osteoporosis.
This starts to make sense when you look at the pro-inflammatory factors that increase with changes in biome diversity, in particular tumor necrosis factor alpha (which is something we also see in inflammatory bowel disease), interleukin-1, and increased activated osteoclasts.
Therefore, when it comes to decreasing bone loss among patients who are perimenopausal or postmenopausal, we don’t yet have a clear answer. Hormone therapy, diet, activity, vitamin D supplementation, and other things may positively change the biome. They are worthy topics for patients to bring up with their ob.gyns. or primary care doctors.
Although it may be a little bit outside the scope of gastroenterology, in my opinion there are a number of new findings relating to menopause that we as a field need to be more proactive in addressing.
Ask the right questions when these people come in to you, irrespective of why they’re there. Start to ask about the quality of their sleep. What are their other functional symptoms? What are their other potential osteoporosis-related risks?
We must do a better job about individualizing care. Rather than treating patients as disease states, we must start to do specific patient-focused care.
I hope this gives you some provocative thoughts when you have your next session with a patient in the perimenopausal or menopausal state. There are lots of things that we continue to learn.
Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology. He serves as an adviser to ISOThrive and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Foreword: VA Research and COVID-19
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Sylvester Norman, a 67-year-old Coast Guard veteran and retired day-care worker from Nashville, Tennessee, volunteered to participate in the US Department of Veterans Affairs (VA) Million Veteran Program (MVP). He and all 4 of his brothers had experienced kidney illness. During the pandemic, Adriana Hung, MD, MPH, an MVP researcher and associate professor of nephrology at Vanderbilt University, noticed that a disproportionate number of Black patients hospitalized with COVID-19 were dying of acute kidney failure. Dr. Hung used data from Norman and other Black veterans provided through the MVP to identify genetic variations in the APOL1 gene linked to kidney disease found in 1 of every 8 people of African descent. Her research proved that a COVID-19 viral infection can trigger these genes and drive a patient’s kidneys to go into failure. Thanks to her research and volunteers like Norman, a new drug targeting APOL1 may soon receive approval from the US Food and Drug Administration (FDA).
This is only one example of the life-saving work conducted by the Veterans Health Administration (VHA) during the pandemic. On January 21, 2020, 1 day after the first confirmed COVID-19 case in the US, the VHA quickly activated its Emergency Management Coordination Cell (EMCC) under a unified command structure with round-the-clock operations to track the evolving risk and plan a response to this once-in-a-century pandemic. A few months later, and before the US declared COVID-19 a pandemic, the VHA research program sprang into action, preparing its community of investigators to address the emerging needs and challenges of the COVID-19 public health crisis. Three years later, although the federal COVID-19 public emergency is declared over, the VHA remains diligent in observing trends and conducting necessary research on the disease as case numbers rise and fall across time.
This special issue of Federal Practitioner showcases the many ways that the VHA successfully leveraged and rapidly mobilized its research enterprise capabilities as part of the national response to COVID-19 and continues to work in this area. As the virus rapidly spread across the country, the VHA research program, overseen by the Office of Research and Development (ORD) and in partnership with other VHA offices, demonstrated the strength and agility that come from being part of a nationwide integrated health care system.
Historically, the VHA has been one of the nation’s leaders in translating medical breakthroughs to the treatment and care of veterans and the nation. Today, the VHA ensures that veterans have increased access to innovative health care solutions by promoting new medical research initiatives, training health care professionals, and developing community partnerships.
As this special issue of Federal Practitioner demonstrates, the VHA’s extraordinary research response to the COVID-19 pandemic was shaped by its ongoing transformation to a full-scale research enterprise; diversity of partnerships with academia, other federal agencies, and industry; extensive infrastructure for funding and quickly ramping up multisite clinical trials; and longstanding partnership with veterans, who volunteer to serve their country twice—first in uniform, and later by volunteering to participate in VA research.
By leveraging these and other assets, VHA investigators have conducted > 900 COVID-19 research projects across 83 VA medical centers, with nearly 3000 VA-affiliated papers published by mid-2023. We have also become a leader in long COVID, generating notable findings using our electronic health record data and filling in the picture with studies that include interviews with thousands of patients, examinations of blood markers, and exploration of the role of genetics. Along the way, the VA collaborated with federal partners, such as the US Department of Defense, by funding a longitudinal research cohort in which 2800 veterans are enrolled. Through this joint effort, researchers will learn more about the natural history and outcomes among veterans affected by COVID-19. This work continues as part of the VA commitment to the health and care of these veterans and nation as a whole.
Additionally, by partnering with veterans, the VA established a research volunteer registry. More than 58,000 veterans volunteered to be contacted to participate in studies if they were eligible. This effort was critical to the VA’s ability to contribute to the vaccine and other therapeutic trials that were seeking approval from the FDA for broader public use. This volunteerism by these veterans showed the nation that the VA is a valuable partner in times of need.
The VA research program remains tightly focused on understanding the long-term impacts of COVID-19. At the same time, the VA is committed to using lessons learned during the crisis in addressing high priorities in veterans’ health care. Among those priorities is fulfilling our mission under the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 to improve care for veterans with military environmental exposures. Over the next few years, VA researchers will analyze health care and epidemiologic data to improve the identification and treatment of medical conditions potentially associated with toxic exposures. This work will include analyses of health trends of post-9/11 veterans, cancer rates among veterans, toxic exposure and mental health outcomes, and the health effects of jet fuels.
Our research program also will support the VA priority of hiring faster and more competitively. With many of the 3700 VA-funded principal investigators also serving as faculty at top universities, VA research programs position us to recruit the best and brightest professionals on the cutting edge of health care. These efforts work hand in hand with the clinical training the VA provides to 113,000 health professions trainees, creating a pipeline of clinicians and physician-researchers for the future. Further, these partnerships strengthen the VA’s ability to expand access by connecting veterans to the best, immediate care.
Finally, VA research will continue to be critical to our top clinical priority of preventing veteran suicide. This area of VA research covers a wide and critically important set of topics, such as the use of predictive modeling to determine veterans most at risk as well as studies on substance use disorders and suicidal ideation, among others.
The impressive collection of articles in this special issue provides a snapshot of the large-scale, all-hands approach the VHA adopted during the COVID-19 public health crisis. I am extremely proud of the work you are about to read.
Right under our noses
Until a couple of weeks ago I considered myself a COVID virgin. I had navigated a full 36 months without a positive test, despite cohabiting with my wife in a 2,500-square-foot house during her bout with the SARS-CoV-2 virus last year. I have been reasonably careful, a situational mask wearer, and good about avoiding poorly ventilated crowded spaces. Of course I was fully vaccinated but was waiting until we had gotten closer to a December trip before getting the newest booster.
I had always been quietly smug about my good luck. And, I was pretty sure that luck had been the major contributor to my run of good health. Nonetheless, in my private moments I often wondered if I somehow had inherited or acquired an unusual defense against the virus that had been getting the best of my peers. One rather far-fetched explanation that kept popping out of my subconscious involved my profuse and persistent runny nose.
Like a fair number in my demographic, I have what I have self-diagnosed as vasomotor rhinitis. In the cooler months and particularly when I am active outdoors, my nose runs like a faucet. I half-jokingly told my wife after a particularly drippy bike ride on a frigid November afternoon that even the most robust virus couldn’t possibly have survived the swim upstream against torrent of mucus splashing onto the handlebars of my bike.
A recent study published in the journal Cell suggests that my off-the-wall explanation for my COVID resistance wasn’t quite so hair-brained. The investigators haven’t found that septuagenarian adults with high-volume runny noses are drowning the SARS-Co- 2 virus before it can do any damage. However, the researchers did discover that, This first line of defense seems to be more effective than in adults, where the virus can more easily slip through into the bloodstream, sometimes with a dramatic release of circulating cytokines, which occasionally create problems of their own. Children also release cytokines, but this is predominantly in their nose, where it appears to be less damaging. Interestingly, in children this initial response persists for around 300 days while in adults the immune response experiences a much more rapid decline. I guess this means we have to chalk one more up for snotty nose kids.
However, the results of this study also suggest that we should be giving more attention to the development of nasal vaccines. I recall that nearly 3 years ago, at the beginning of the pandemic, scientists using a ferret model had developed an effective nasal vaccine. I’m not sure why this faded out of the picture, but it feels like it’s time to turn the spotlight on this line of research again.
I suspect that in addition to being more effective, a nasal vaccine may gain more support among the antivaxxer population, many of whom I suspect are really needle phobics hiding behind a smoke screen of anti-science double talk.
At any rate, I will continue to search for articles that support my contention that my high-flow rhinorrhea is protecting me. I have always been told that a cold nose was the sign of a healthy dog. I’m just trying to prove that the same is true for us old guys with clear runny noses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Until a couple of weeks ago I considered myself a COVID virgin. I had navigated a full 36 months without a positive test, despite cohabiting with my wife in a 2,500-square-foot house during her bout with the SARS-CoV-2 virus last year. I have been reasonably careful, a situational mask wearer, and good about avoiding poorly ventilated crowded spaces. Of course I was fully vaccinated but was waiting until we had gotten closer to a December trip before getting the newest booster.
I had always been quietly smug about my good luck. And, I was pretty sure that luck had been the major contributor to my run of good health. Nonetheless, in my private moments I often wondered if I somehow had inherited or acquired an unusual defense against the virus that had been getting the best of my peers. One rather far-fetched explanation that kept popping out of my subconscious involved my profuse and persistent runny nose.
Like a fair number in my demographic, I have what I have self-diagnosed as vasomotor rhinitis. In the cooler months and particularly when I am active outdoors, my nose runs like a faucet. I half-jokingly told my wife after a particularly drippy bike ride on a frigid November afternoon that even the most robust virus couldn’t possibly have survived the swim upstream against torrent of mucus splashing onto the handlebars of my bike.
A recent study published in the journal Cell suggests that my off-the-wall explanation for my COVID resistance wasn’t quite so hair-brained. The investigators haven’t found that septuagenarian adults with high-volume runny noses are drowning the SARS-Co- 2 virus before it can do any damage. However, the researchers did discover that, This first line of defense seems to be more effective than in adults, where the virus can more easily slip through into the bloodstream, sometimes with a dramatic release of circulating cytokines, which occasionally create problems of their own. Children also release cytokines, but this is predominantly in their nose, where it appears to be less damaging. Interestingly, in children this initial response persists for around 300 days while in adults the immune response experiences a much more rapid decline. I guess this means we have to chalk one more up for snotty nose kids.
However, the results of this study also suggest that we should be giving more attention to the development of nasal vaccines. I recall that nearly 3 years ago, at the beginning of the pandemic, scientists using a ferret model had developed an effective nasal vaccine. I’m not sure why this faded out of the picture, but it feels like it’s time to turn the spotlight on this line of research again.
I suspect that in addition to being more effective, a nasal vaccine may gain more support among the antivaxxer population, many of whom I suspect are really needle phobics hiding behind a smoke screen of anti-science double talk.
At any rate, I will continue to search for articles that support my contention that my high-flow rhinorrhea is protecting me. I have always been told that a cold nose was the sign of a healthy dog. I’m just trying to prove that the same is true for us old guys with clear runny noses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Until a couple of weeks ago I considered myself a COVID virgin. I had navigated a full 36 months without a positive test, despite cohabiting with my wife in a 2,500-square-foot house during her bout with the SARS-CoV-2 virus last year. I have been reasonably careful, a situational mask wearer, and good about avoiding poorly ventilated crowded spaces. Of course I was fully vaccinated but was waiting until we had gotten closer to a December trip before getting the newest booster.
I had always been quietly smug about my good luck. And, I was pretty sure that luck had been the major contributor to my run of good health. Nonetheless, in my private moments I often wondered if I somehow had inherited or acquired an unusual defense against the virus that had been getting the best of my peers. One rather far-fetched explanation that kept popping out of my subconscious involved my profuse and persistent runny nose.
Like a fair number in my demographic, I have what I have self-diagnosed as vasomotor rhinitis. In the cooler months and particularly when I am active outdoors, my nose runs like a faucet. I half-jokingly told my wife after a particularly drippy bike ride on a frigid November afternoon that even the most robust virus couldn’t possibly have survived the swim upstream against torrent of mucus splashing onto the handlebars of my bike.
A recent study published in the journal Cell suggests that my off-the-wall explanation for my COVID resistance wasn’t quite so hair-brained. The investigators haven’t found that septuagenarian adults with high-volume runny noses are drowning the SARS-Co- 2 virus before it can do any damage. However, the researchers did discover that, This first line of defense seems to be more effective than in adults, where the virus can more easily slip through into the bloodstream, sometimes with a dramatic release of circulating cytokines, which occasionally create problems of their own. Children also release cytokines, but this is predominantly in their nose, where it appears to be less damaging. Interestingly, in children this initial response persists for around 300 days while in adults the immune response experiences a much more rapid decline. I guess this means we have to chalk one more up for snotty nose kids.
However, the results of this study also suggest that we should be giving more attention to the development of nasal vaccines. I recall that nearly 3 years ago, at the beginning of the pandemic, scientists using a ferret model had developed an effective nasal vaccine. I’m not sure why this faded out of the picture, but it feels like it’s time to turn the spotlight on this line of research again.
I suspect that in addition to being more effective, a nasal vaccine may gain more support among the antivaxxer population, many of whom I suspect are really needle phobics hiding behind a smoke screen of anti-science double talk.
At any rate, I will continue to search for articles that support my contention that my high-flow rhinorrhea is protecting me. I have always been told that a cold nose was the sign of a healthy dog. I’m just trying to prove that the same is true for us old guys with clear runny noses.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Heart rate variability: Are we ignoring a harbinger of health?
A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.
Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?
A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.
More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
What is HRV?
HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.
Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.
As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.
That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
Why monitor HRV?
But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.
Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.
The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.
To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.
I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.
A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.
Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.
My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.
Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.
Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.
Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.
I don’t plan to receive my flu and COVID vaccines on the same day again.
So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.
I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.
Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.
George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.
A version of this article first appeared on Medscape.com.
A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.
Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?
A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.
More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
What is HRV?
HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.
Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.
As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.
That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
Why monitor HRV?
But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.
Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.
The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.
To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.
I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.
A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.
Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.
My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.
Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.
Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.
Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.
I don’t plan to receive my flu and COVID vaccines on the same day again.
So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.
I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.
Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.
George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.
A version of this article first appeared on Medscape.com.
A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.
Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?
A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.
More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
What is HRV?
HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.
Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.
As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.
That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
Why monitor HRV?
But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.
Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.
The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.
To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.
I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.
A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.
Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.
My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.
Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.
Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.
Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.
I don’t plan to receive my flu and COVID vaccines on the same day again.
So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.
I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.
Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.
George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.
A version of this article first appeared on Medscape.com.
Q&A: Cancer screening in older patients – who to screen and when to stop
More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.
Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?
Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.
We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.
But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?
A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.
However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?
A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.
Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?
A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.
For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.
I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?
A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?
A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *
Q: What role do the multicancer blood and DNA tests play in screening now?
A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.
The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.
There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?
A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
Q: Anything else you’d like to say on this subject that clinicians should know?
A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.
There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.
My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.
*This story was updated on Nov. 1, 2023.
More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.
Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?
Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.
We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.
But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?
A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.
However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?
A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.
Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?
A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.
For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.
I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?
A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?
A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *
Q: What role do the multicancer blood and DNA tests play in screening now?
A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.
The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.
There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?
A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
Q: Anything else you’d like to say on this subject that clinicians should know?
A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.
There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.
My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.
*This story was updated on Nov. 1, 2023.
More than 1 in 10 Americans over age 60 years will be diagnosed with cancer, according to the National Cancer Institute, making screening for the disease in older patients imperative. Much of the burden of cancer screening falls on primary care physicians. This news organization spoke recently with William L. Dahut, MD, chief scientific officer of the American Cancer Society, about the particular challenges of screening in older patients.
Question: How much does cancer screening change with age? What are the considerations for clinicians – what risks and comorbidities are important to consider in older populations?
Answer: We at the American Cancer Society are giving a lot of thought to how to help primary care practices keep up with screening, particularly with respect to guidelines, but also best practices where judgment is required, such as cancer screening in their older patients.
We’ve had a lot of conversations recently about cancer risk in the young, largely because data show rates are going up for colorectal and breast cancer in this population. But it’s not one size fits all. Screening for young women who have a BRCA gene, if they have dense breasts, or if they have a strong family history of breast cancer should be different from those who are at average risk of the disease.
But statistically, there are about 15 per 100,000 breast cancer diagnoses in women under the age of 40 while over the age of 65 it’s 443 per 100,000. So, the risk significantly increases with age but we should not have an arbitrary cut-off. The life expectancy of a woman at age 75 is about 13.5 years. If you’re over the age of 70 or 75, then it’s going to be comorbidities that you look at, as well as individual patient decisions. Patients may say, “I don’t want to ever go through a mammogram again, because I don’t want to have a biopsy again, and I’m not going to get treated.” Or they may say, “My mom died of metastatic breast cancer when she was 82 and I want to know.”
Q: How should primary care physicians interpret conflicting guidance from the major medical groups? For example, the American College of Gastroenterology and your own organization recommend colorectal cancer screening start at age 45 now. But the American College of Physicians recently came out and said 50. What is a well-meaning primary care physician supposed to do?
A: We make more of guideline differences than we should. Sometimes guideline differences aren’t a reflection of different judgments, but rather what data were available when the most recent update took place. For colorectal cancer screening, the ACS dropped the age to begin screening to 45 in 2018 based on a very careful consideration of disease burden data and within several years most other guideline developers reached the same conclusion.
However, I think it’s good for family practice and internal medicine doctors to know that significant GI symptoms in a young patient could be colorectal cancer. It’s not as if nobody sees a 34-year-old or 27-year-old with colorectal cancer. They should be aware that if something goes away in a day or two, that’s fine, but persistent GI symptoms need a cancer workup – colonoscopy or referral to a gastroenterologist. So that’s why I think age 45 is the time when folks should begin screening.
Q: What are the medical-legal issues for a physician who is trying to follow guideline-based care when there are different guidelines?
A: Any physician can say, “We follow the guidelines of this particular organization.” I don’t think anyone can say that an organization’s guidelines are malpractice. For individual physicians, following a set of office-based guidelines will hopefully keep them out of legal difficulty.
Q: What are the risks of overscreening, especially in breast cancer where false positives may result in invasive testing?
A: What people think of as overscreening takes a number of different forms. What one guideline would imply is overscreening is recommended screening by another guideline. I think we would all agree that in an average-risk population, beginning screening before it is recommended would be overscreening, and continuing screening when a patient has life-limiting comorbidities would constitute overscreening. Screening too frequently can constitute overscreening.
For example, many women report that their doctors still are advising a baseline mammogram at age 35. Most guideline-developing organizations would regard this as overscreening in an average-risk population.
I think we are also getting better, certainly in prostate cancer, about knowing who needs to be treated and not treated. There are a lot of cancers that would have been treated 20-30 years ago but now are being safely followed with PSA and MRI. We may be able to get to that point with breast cancer over time, too.
Q: Are you saying that there may be breast cancers for which active surveillance is appropriate? Is that already the case?
A: We’re not there yet. I think some of the DCIS breast cancers are part of the discussion on whether hormonal treatment or surgeries are done. I think people do have those discussions in the context of morbidity and life expectancy. Over time, we’re likely to have more cancers for which we won’t need surgical treatments.
Q: Why did the American Cancer Society change the upper limit for lung cancer screening from 75 to 80 years of age?
A: For an individual older than 65, screening will now continue until the patient is 80, assuming the patient is in good health. According to the previous guideline, if a patient was 65 and more than 15 years beyond smoking cessation, then screening would end. This is exactly the time when we see lung cancers increase in the population and so a curable lung cancer would not previously have been detected by a screening CT scan. *
Q: What role do the multicancer blood and DNA tests play in screening now?
A: As you know, the Exact Sciences Cologuard test is already included in major guidelines for colorectal cancer screening and covered by insurance. Our philosophy on multicancer early detection tests is that we’re supportive of Medicare reimbursement when two things occur: 1. When we know there’s clinical benefit, and 2. When the test has been approved by the FDA.
The multicancer early detection tests in development and undergoing prospective research would not now replace screening for the cancers with established screening programs, but if they are shown to have clinical utility for the cancers in their panel, we would be able to reduce deaths from cancers that mostly are diagnosed at late stages and have poor prognoses.
There’s going to be a need for expertise in primary care practices to help interpret the tests. These are new questions, which are well beyond what even the typical oncologist is trained in, much less primary care physicians. We and other organizations are working on providing those answers.
Q: While we’re on the subject of the future, how do you envision AI helping or hindering cancer screening specifically in primary care?
A: I think AI is going to help things for a couple of reasons. The ability of AI is to get through data quickly and get you information that’s personalized and useful. If AI tools could let a patient know their individual risk of a cancer in the near and long term, that would help the primary care doctor screen in an individualized way. I think AI is going to be able to improve both diagnostic radiology and pathology, and could make a very big difference in settings outside of large cancer centers that operate at high volume every day. The data look very promising for AI to contribute to risk estimation by operating like a second reader in imaging and pathology.
Q: Anything else you’d like to say on this subject that clinicians should know?
A: The questions about whether or not patients should be screened is being pushed on family practice doctors and internists and these questions require a relationship with the patient. A hard stopping point at age 70 when lots of people will live 20 years or more doesn’t make sense.
There’s very little data from randomized clinical trials of screening people over the age of 70. We know that cancer risk does obviously increase with age, particularly prostate and breast cancer. And these are the cancers that are going to be the most common in your practices. If someone has a known mutation, I think you’re going to look differently at screening them. And first-degree family members, particularly for the more aggressive cancers, should be considered for screening.
My philosophy on cancer screening in the elderly is that I think the guidelines are guidelines. If patients have very limited life expectancy, then they shouldn’t be screened. There are calculators that estimate life expectancy in the context of current age and current health status, and these can be useful for decision making and counseling. Patients never think their life expectancy is shorter than 10 years. If their life expectancy is longer than 10 years, then I think, all things being equal, they should continue screening, but the question of ongoing screening needs to be periodically revisited.
*This story was updated on Nov. 1, 2023.