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How physicians can provide better care to transgender patients
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
Steroid-refractory pneumonitis from ICIs: Experience at major centers
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
U.S. finally hits its stride with COVID-19 vaccination rollouts
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Enzymatic injections show durable improvement in buttock cellulite
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
FROM INNOVATIONS IN DERMATOLOGY
Arkansas first state to ban transgender medical treatments for youths
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Contradictions abound in ‘The End of Mental Illness’
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Everyday chemicals are linked to declines in human fertility
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Implementation of a Pharmacist-Managed Transitions of Care Tool
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
What’s the future of telehealth? It’s ‘complicated’
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
FROM THE SPD PRE-AAD MEETING
Gastrointestinal Symptoms and Lactic Acidosis in a Chronic Marijuana User
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048