Perspectives

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

It’s a “champagne problem” many of us have encountered over the past few years in the clinic.

A patient with advanced non–small cell lung cancer (NSCLC) is fortunate enough to continue to do well for 2 years on ongoing pembrolizumab or perhaps pemetrexed and pembrolizumab as maintenance therapy. The latest CT shows a residual but far smaller primary tumor than what she started with.

In this instance, you may be considering stopping treatment but are concerned about doing so with evidence of disease still present.

Clinical trials of immunotherapy or chemoimmunotherapy have generally terminated treatment in nonprogressing patients after 2 years. We also know that some patients in early trials of immunotherapy stopped treatment after a fixed period of 1 or 2 years and continued to show no evidence of progression many years later.

The reason some patients experience this kind of success: Unlike the mechanism of action of conventional chemotherapy or targeted therapies, where ongoing treatment would be important to continue to exert an inhibitory effect, the active substrate of immunotherapy is the patient’s immune system, which can potentially have a self-sustaining efficacy beyond the stimulatory effect of the checkpoint inhibitor.

Though we don’t want to overtreat our patients, the question remains: Will patients do just as well off treatment, with the potential to resume as needed?

One trial directly addressed this question of stopping vs. continuing treatment in patients on immunotherapy. The CheckMate 153 trial, published in 2020, randomly assigned 252 previously treated patients who hadn’t demonstrated progression after 1 year on nivolumab to either discontinue nivolumab or continue nivolumab on an ongoing basis. The results were strongly in favor of ongoing therapy. Both progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who continued therapy: PFS of 24.7 months vs. 9.4 months and OS not reached vs. 32.5 months.

This finding is important, but there’s an important caveat. The study population included many heavily pretreated patients, but, in practice, immunotherapy has generally moved into the first-line setting, where we see dramatic responses in a significant subset of patients.

Even more recent data are emerging that may help us evaluate who will do well off therapy and who should continue treatment.

We now have a growing collection of long-term data on patients who are more likely to have good outcomes with immunotherapy, specifically those with high tumor programmed death-ligand 1 (PD-L1) expression (≥ 50%), from the KEYNOTE-024 trial. In this study, 39 of 151 (25.8%) patients assigned to pembrolizumab completed the planned maximum of 2 years of treatment, among whom 82.1% achieved an objective response; but, only 10% (4 patients) achieved a complete response. The proportion of patients without progression and remaining off therapy wasn’t reported, but the OS rate 3 years after completing treatment was 81.4%.

In addition, restarting immunotherapy after discontinuing appears to be a moderately effective strategy. In the KEYNOTE-024 trial, 12 patients received a second course of pembrolizumab because of disease progression a median of 15.2 months after discontinuing pembrolizumab. In this small cohort, eight of these patients (66.7%) were alive at the data cutoff, and six (50%) achieved stable disease.

Recently, we received additional insight in the follow-up from two chemoimmunotherapy trials that have most shaped my practice for patients with advanced NSCLC and any level of PD-L1 expression. These are the KEYNOTE-189 trial of platinum-pemetrexed with pembrolizumab vs. placebo in those with nonsquamous NSCLC, and the KEYNOTE-407 trial of carboplatin-taxane with pembrolizumab vs. placebo in patients with advanced squamous NSCLC. The National Comprehensive Cancer Network has designated each as a “preferred regimen” for patients with advanced NSCLC.

Both regimens have demonstrated sustained efficacy benefits with prolonged follow-up, including significantly superior objective response rate, PFS, and OS with the addition of pembrolizumab. These findings merely cemented the role of these regimens in our practice, but the trials also reported on the cohort of patients who completed 35 cycles of treatment over 2 years then discontinued therapy. In both, the majority of patients showed an objective response (86% in KEYNOTE-189 and 90% in KEYNOTE-407), with most patients alive at 3 years after 2 years of treatment (71.9% in KEYNOTE-189 and 69.5% in KEYNOTE-407). In addition, the proportion of patients alive without disease progression or subsequent therapy was notable – 40.4% in KEYNOTE-189 and 43.6% KEYNOTE-407.

How should we interpret these data for the patient who is in the exam room with us?

The short answer is that we don’t know. I see this as a half-empty, half-full conundrum.

I’m disappointed that more patients who responded for 2 years will experience disease progression in the 1-3 years that follow. This signals that their immune systems have not perpetuated their initial response over the long-term. But these patients may have demonstrated disease progression even if they had continued therapy.

We also know that some patients can be rechallenged and will respond again. Some of these patients will show stable disease, whereas others will progress with repeat treatment. I would love to be able to better predict which patients are destined to do well without treatment vs. those who benefit from treatment beyond 2 years.

Might the level of PD-L1 expression tell us? Can PET imaging discriminate those with residual hypermetabolism who may need continued treatment from those with no residual uptake who could be spared it? Would serial measurement of circulating tumor DNA (ctDNA) in responding patients identify when they have achieved a point of diminishing returns, potentially indicating that some can safely discontinue treatment after 2 years, whereas others need to continue to suppress on prolonged maintenance therapy?

These questions have yet to be studied systematically. In the meantime, I take an individualized approach with my patients facing this decision. Some have experienced escalating arthralgias and myalgias, cost concerns, or other issues related to immunotherapy that may dissuade us from continuing treatment. But several others have been grateful to continue with their treatment, hesitant to do anything that could change the path of their disease.

In my patients who tolerate therapy well, I’m more worried about potential undertreatment than overtreatment. I tend to favor having my patients continue therapy in the absence of problematic toxicity or practical challenges. There is certainly room for debate here while we await data to better guide these decisions. How do you approach these patients?

Dr. West is Clinical Associate Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Care, Duarte, Calif. He reported conflicts of interest with Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, Merck, and Eli Lilly.

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

In September, the World Professional Association for Transgender Health released its much-anticipated standards of care (SOC8). While this update has unfortunately received intense scrutiny for its guidance about gender-diverse adolescents and youth, the SOC8 is their most evidence-based version to date. Recommendations were developed based on data from independent systematic literature reviews, background reviews, and expert opinions.¹ These guidelines also recognize knowledge deficits and are intended to be flexible to meet the individual needs of transgender patients. While the scope of this column will not delve into all 258 pages of these new standards, it will highlight pertinent information on hormonal management.

Ever since the original publication of the standards of care in 1979, gender-affirming hormone therapy (GAHT) has been considered medically necessary. The approach to GAHT depends on the patient’s goals and the age at which the patient is seeking to medically transition. Given the complexity of GAHT for transgender youth and adolescents, this article will focus primarily on adult patients.

There are a few pertinent differences in the management and monitoring of GAHT in adults. For patients assigned female at birth, testosterone is the primary modality by which patients can achieve masculinizing features. GAHT for patients assigned male at birth often consists of estrogen and an androgen-lowering medication. Like its predecessor, SOC8 recommends against prescribing ethinyl estradiol because of its marked association with thromboembolic events.

While the formulations of estrogen (oral, injectable, and patches) and hormone blockers (finasteride, spironolactone, gonadotropin-releasing hormone agonists, and bicalutamide) are discussed in prior standards of care, SOC8 further delineates their utilization. It suggests that transdermal estrogen should be considered in transgender women over the age of 45 who are at high risk for developing a venous thromboembolism or have a previous history of thromboembolism. Furthermore, SOC8 establishes spironolactone as the mainstay for androgen blockage and discourages routine usage of bicalutamide and finasteride because of a lack of safety data and questionable efficacy.¹ Even though some patients anecdotally report increased breast growth with progesterone supplementation, there is insufficient evidence to regularly prescribe progesterone for breast development.¹

Both WPATH and the Endocrine Society recommend checking serum levels of sex hormones every 3 months during the first year until stable levels are achieved, then once or twice a year thereafter.¹ Hormone levels should be maintained at physiologic concentrations of the targeted gender. Some patients on feminizing GAHT often request evaluation of estrone/estradiol ratios as there was an assumption that higher ratios were associated with antagonistic effects on breast development. However, recent published evidence refutes this claim and estrone/estradiol ratios need not be measured.¹

In addition to monitoring sex hormone levels, providers should check the metabolic effects that can be associated with GAHT. Both testosterone and estrogen can influence lipid panels: Testosterone can increase the red blood cell count, and spironolactone may cause hyperkalemia. While the SOC7 previously encouraged assessment of these laboratory values every 3 months, the new guidelines are more flexible in the frequency of testing of asymptomatic individuals as there is no strong evidence from published studies that supports these 3-month intervals.¹

Providers are responsible for informing patients about the possible effects of GAHT on fertility. Estrogen often will cause a reduction in spermatogenesis, which may be irreversible. Patients who plan on taking estrogen should be counseled regarding sperm cryopreservation prior to starting GAHT. Even though testosterone inhibits ovulation and induces menstrual suppression, patients often regain their fertility after cessation of testosterone therapy. However, given the significant knowledge deficit about long-term fertility in transmasculine patients, providers should still offer oocyte or embryo cryopreservation.

Health care providers should collaborate with surgeons regarding preoperative and postoperative GAHT. To mitigate the risk of thromboembolism, many surgeons would stop hormones 1-4 weeks before and after gender-affirming surgery. Recent evidence does not support this practice, as studies indicate no increased risk for venous thromboembolism in individuals on GAHT undergoing surgery. These studies are consistent with other well-established guidelines on preoperative management of cisgender women taking estrogen or progestins. As exogenous sex steroids are necessary for bone health in patients who undergo gonadectomy, surgeons and other health care providers should educate patients on the importance of continuing GAHT.

There are many procedures available for gender-affirming surgery. Many of these surgeries involve three regions: the face, chest/breast, and/or genitalia (both internal and external). Prior to making a surgical referral, providers should be familiar with the surgeon’s scope of practice, performance measures, and surgical outcomes.¹ For the first time, the SOC8 also addresses the surgical training of the providers who offer these procedures. While gender-affirming surgery can be performed by a variety of different specialists, training and documented supervision (often by an existing expert in gender-affirming surgery) is essential. Maintaining an active practice in these procedures, tracking surgical outcomes, and continuing education within the field of gender-affirming surgery are additional requirements for surgeons performing these complex operations.¹

As their name implies, the SOC8 attempts to create a standardized guide to assist practitioners caring for gender-diverse patients. It’s important for providers to be familiar with updates while also recognizing the evolving nature of this rapidly growing field.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

Reference

1. World Professional Association for Transgender Health. Standards of care for the health of transgender and gender diverse people, Version 8. Int J Transgend Health. 2022 Sep 15. doi: 10.1080/26895269.2022.2100644.

In September, the World Professional Association for Transgender Health released its much-anticipated standards of care (SOC8). While this update has unfortunately received intense scrutiny for its guidance about gender-diverse adolescents and youth, the SOC8 is their most evidence-based version to date. Recommendations were developed based on data from independent systematic literature reviews, background reviews, and expert opinions.¹ These guidelines also recognize knowledge deficits and are intended to be flexible to meet the individual needs of transgender patients. While the scope of this column will not delve into all 258 pages of these new standards, it will highlight pertinent information on hormonal management.

Ever since the original publication of the standards of care in 1979, gender-affirming hormone therapy (GAHT) has been considered medically necessary. The approach to GAHT depends on the patient’s goals and the age at which the patient is seeking to medically transition. Given the complexity of GAHT for transgender youth and adolescents, this article will focus primarily on adult patients.

There are a few pertinent differences in the management and monitoring of GAHT in adults. For patients assigned female at birth, testosterone is the primary modality by which patients can achieve masculinizing features. GAHT for patients assigned male at birth often consists of estrogen and an androgen-lowering medication. Like its predecessor, SOC8 recommends against prescribing ethinyl estradiol because of its marked association with thromboembolic events.

While the formulations of estrogen (oral, injectable, and patches) and hormone blockers (finasteride, spironolactone, gonadotropin-releasing hormone agonists, and bicalutamide) are discussed in prior standards of care, SOC8 further delineates their utilization. It suggests that transdermal estrogen should be considered in transgender women over the age of 45 who are at high risk for developing a venous thromboembolism or have a previous history of thromboembolism. Furthermore, SOC8 establishes spironolactone as the mainstay for androgen blockage and discourages routine usage of bicalutamide and finasteride because of a lack of safety data and questionable efficacy.¹ Even though some patients anecdotally report increased breast growth with progesterone supplementation, there is insufficient evidence to regularly prescribe progesterone for breast development.¹

Both WPATH and the Endocrine Society recommend checking serum levels of sex hormones every 3 months during the first year until stable levels are achieved, then once or twice a year thereafter.¹ Hormone levels should be maintained at physiologic concentrations of the targeted gender. Some patients on feminizing GAHT often request evaluation of estrone/estradiol ratios as there was an assumption that higher ratios were associated with antagonistic effects on breast development. However, recent published evidence refutes this claim and estrone/estradiol ratios need not be measured.¹

In addition to monitoring sex hormone levels, providers should check the metabolic effects that can be associated with GAHT. Both testosterone and estrogen can influence lipid panels: Testosterone can increase the red blood cell count, and spironolactone may cause hyperkalemia. While the SOC7 previously encouraged assessment of these laboratory values every 3 months, the new guidelines are more flexible in the frequency of testing of asymptomatic individuals as there is no strong evidence from published studies that supports these 3-month intervals.¹

Providers are responsible for informing patients about the possible effects of GAHT on fertility. Estrogen often will cause a reduction in spermatogenesis, which may be irreversible. Patients who plan on taking estrogen should be counseled regarding sperm cryopreservation prior to starting GAHT. Even though testosterone inhibits ovulation and induces menstrual suppression, patients often regain their fertility after cessation of testosterone therapy. However, given the significant knowledge deficit about long-term fertility in transmasculine patients, providers should still offer oocyte or embryo cryopreservation.

Health care providers should collaborate with surgeons regarding preoperative and postoperative GAHT. To mitigate the risk of thromboembolism, many surgeons would stop hormones 1-4 weeks before and after gender-affirming surgery. Recent evidence does not support this practice, as studies indicate no increased risk for venous thromboembolism in individuals on GAHT undergoing surgery. These studies are consistent with other well-established guidelines on preoperative management of cisgender women taking estrogen or progestins. As exogenous sex steroids are necessary for bone health in patients who undergo gonadectomy, surgeons and other health care providers should educate patients on the importance of continuing GAHT.

There are many procedures available for gender-affirming surgery. Many of these surgeries involve three regions: the face, chest/breast, and/or genitalia (both internal and external). Prior to making a surgical referral, providers should be familiar with the surgeon’s scope of practice, performance measures, and surgical outcomes.¹ For the first time, the SOC8 also addresses the surgical training of the providers who offer these procedures. While gender-affirming surgery can be performed by a variety of different specialists, training and documented supervision (often by an existing expert in gender-affirming surgery) is essential. Maintaining an active practice in these procedures, tracking surgical outcomes, and continuing education within the field of gender-affirming surgery are additional requirements for surgeons performing these complex operations.¹

As their name implies, the SOC8 attempts to create a standardized guide to assist practitioners caring for gender-diverse patients. It’s important for providers to be familiar with updates while also recognizing the evolving nature of this rapidly growing field.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

Reference

1. World Professional Association for Transgender Health. Standards of care for the health of transgender and gender diverse people, Version 8. Int J Transgend Health. 2022 Sep 15. doi: 10.1080/26895269.2022.2100644.

In September, the World Professional Association for Transgender Health released its much-anticipated standards of care (SOC8). While this update has unfortunately received intense scrutiny for its guidance about gender-diverse adolescents and youth, the SOC8 is their most evidence-based version to date. Recommendations were developed based on data from independent systematic literature reviews, background reviews, and expert opinions.¹ These guidelines also recognize knowledge deficits and are intended to be flexible to meet the individual needs of transgender patients. While the scope of this column will not delve into all 258 pages of these new standards, it will highlight pertinent information on hormonal management.

Ever since the original publication of the standards of care in 1979, gender-affirming hormone therapy (GAHT) has been considered medically necessary. The approach to GAHT depends on the patient’s goals and the age at which the patient is seeking to medically transition. Given the complexity of GAHT for transgender youth and adolescents, this article will focus primarily on adult patients.

There are a few pertinent differences in the management and monitoring of GAHT in adults. For patients assigned female at birth, testosterone is the primary modality by which patients can achieve masculinizing features. GAHT for patients assigned male at birth often consists of estrogen and an androgen-lowering medication. Like its predecessor, SOC8 recommends against prescribing ethinyl estradiol because of its marked association with thromboembolic events.

While the formulations of estrogen (oral, injectable, and patches) and hormone blockers (finasteride, spironolactone, gonadotropin-releasing hormone agonists, and bicalutamide) are discussed in prior standards of care, SOC8 further delineates their utilization. It suggests that transdermal estrogen should be considered in transgender women over the age of 45 who are at high risk for developing a venous thromboembolism or have a previous history of thromboembolism. Furthermore, SOC8 establishes spironolactone as the mainstay for androgen blockage and discourages routine usage of bicalutamide and finasteride because of a lack of safety data and questionable efficacy.¹ Even though some patients anecdotally report increased breast growth with progesterone supplementation, there is insufficient evidence to regularly prescribe progesterone for breast development.¹

Both WPATH and the Endocrine Society recommend checking serum levels of sex hormones every 3 months during the first year until stable levels are achieved, then once or twice a year thereafter.¹ Hormone levels should be maintained at physiologic concentrations of the targeted gender. Some patients on feminizing GAHT often request evaluation of estrone/estradiol ratios as there was an assumption that higher ratios were associated with antagonistic effects on breast development. However, recent published evidence refutes this claim and estrone/estradiol ratios need not be measured.¹

In addition to monitoring sex hormone levels, providers should check the metabolic effects that can be associated with GAHT. Both testosterone and estrogen can influence lipid panels: Testosterone can increase the red blood cell count, and spironolactone may cause hyperkalemia. While the SOC7 previously encouraged assessment of these laboratory values every 3 months, the new guidelines are more flexible in the frequency of testing of asymptomatic individuals as there is no strong evidence from published studies that supports these 3-month intervals.¹

Providers are responsible for informing patients about the possible effects of GAHT on fertility. Estrogen often will cause a reduction in spermatogenesis, which may be irreversible. Patients who plan on taking estrogen should be counseled regarding sperm cryopreservation prior to starting GAHT. Even though testosterone inhibits ovulation and induces menstrual suppression, patients often regain their fertility after cessation of testosterone therapy. However, given the significant knowledge deficit about long-term fertility in transmasculine patients, providers should still offer oocyte or embryo cryopreservation.

Health care providers should collaborate with surgeons regarding preoperative and postoperative GAHT. To mitigate the risk of thromboembolism, many surgeons would stop hormones 1-4 weeks before and after gender-affirming surgery. Recent evidence does not support this practice, as studies indicate no increased risk for venous thromboembolism in individuals on GAHT undergoing surgery. These studies are consistent with other well-established guidelines on preoperative management of cisgender women taking estrogen or progestins. As exogenous sex steroids are necessary for bone health in patients who undergo gonadectomy, surgeons and other health care providers should educate patients on the importance of continuing GAHT.

There are many procedures available for gender-affirming surgery. Many of these surgeries involve three regions: the face, chest/breast, and/or genitalia (both internal and external). Prior to making a surgical referral, providers should be familiar with the surgeon’s scope of practice, performance measures, and surgical outcomes.¹ For the first time, the SOC8 also addresses the surgical training of the providers who offer these procedures. While gender-affirming surgery can be performed by a variety of different specialists, training and documented supervision (often by an existing expert in gender-affirming surgery) is essential. Maintaining an active practice in these procedures, tracking surgical outcomes, and continuing education within the field of gender-affirming surgery are additional requirements for surgeons performing these complex operations.¹

As their name implies, the SOC8 attempts to create a standardized guide to assist practitioners caring for gender-diverse patients. It’s important for providers to be familiar with updates while also recognizing the evolving nature of this rapidly growing field.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

Reference

1. World Professional Association for Transgender Health. Standards of care for the health of transgender and gender diverse people, Version 8. Int J Transgend Health. 2022 Sep 15. doi: 10.1080/26895269.2022.2100644.

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Vulvar squamous cell carcinomas (VSCC) comprise approximately 90% of all vulvar malignancies. Unlike cervical SCC, which are predominantly human papilloma virus (HPV) positive, only a minority of VSCC are HPV positive – on the order of 15%-25% of cases. Most cases occur in the setting of lichen sclerosus and are HPV negative.

Lichen sclerosus is a chronic inflammatory dermatitis typically involving the anogenital area, which in some cases can become seriously distorted (e.g. atrophy of the labia minora, clitoral phimosis, and introital stenosis). Although most cases are diagnosed in postmenopausal women, LS can affect women of any age. The true prevalence of lichen sclerosus is unknown. Recent studies have shown a prevalence of 1 in 60; among older women, it can even be as high as 1 in 30. While lichen sclerosus is a pruriginous condition, it is often asymptomatic. It is not considered a premalignant condition. The diagnosis is clinical; however, suspicious lesions (erosions/ulcerations, hyperkeratosis, pigmented areas, ecchymosis, warty or papular lesions), particularly when recalcitrant to adequate first-line therapy, should be biopsied.

VSCC arises from precursor lesions or high-grade vulvar intraepithelial neoplasia (VIN). The 2015 International Society for the Study of Vulvovaginal Disease nomenclature classifies high-grade VIN into high-grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN). Most patients with high-grade VIN are diagnosed with HSIL or usual type VIN. A preponderance of these lesions (75%-85%) are HPV positive, predominantly HPV 16. Vulvar HSIL (vHSIL) lesions affect younger women. The lesions tend to be multifocal and extensive. On the other hand, dVIN typically affects older women and commonly develops as a solitary lesion. While dVIN accounts for only a small subset of patients with high-grade VIN, these lesions are HPV negative and associated with lichen sclerosus.

Both disease entities, vHSIL and dVIN, are increasing in incidence. There is a higher risk and shortened period of progression to cancer in patients with dVIN compared to HSIL. The cancer risk of vHSIL is relatively low. The 10-year cumulative VSCC risk reported in the literature is 10.3%; 9.7% for vHSIL and 50% for dVIN. Patients with vHSIL could benefit from less aggressive treatment modalities.

Dr. Jackson-Moore is associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the university.
 

References

Cendejas BR et al. Am J Obstet Gynecol. 2015 Mar;212(3):291-7.

Lebreton M et al. J Gynecol Obstet Hum Reprod. 2020 Nov;49(9):101801.

Thuijs NB et al. Int J Cancer. 2021 Jan 1;148(1):90-8. doi: 10.1002/ijc.33198. .

Trutnovsky G et al. Lancet. 2022 May 7;399(10337):1790-8. Erratum in: Lancet. 2022 Oct 8;400(10359):1194.

Vulvar squamous cell carcinomas (VSCC) comprise approximately 90% of all vulvar malignancies. Unlike cervical SCC, which are predominantly human papilloma virus (HPV) positive, only a minority of VSCC are HPV positive – on the order of 15%-25% of cases. Most cases occur in the setting of lichen sclerosus and are HPV negative.

Lichen sclerosus is a chronic inflammatory dermatitis typically involving the anogenital area, which in some cases can become seriously distorted (e.g. atrophy of the labia minora, clitoral phimosis, and introital stenosis). Although most cases are diagnosed in postmenopausal women, LS can affect women of any age. The true prevalence of lichen sclerosus is unknown. Recent studies have shown a prevalence of 1 in 60; among older women, it can even be as high as 1 in 30. While lichen sclerosus is a pruriginous condition, it is often asymptomatic. It is not considered a premalignant condition. The diagnosis is clinical; however, suspicious lesions (erosions/ulcerations, hyperkeratosis, pigmented areas, ecchymosis, warty or papular lesions), particularly when recalcitrant to adequate first-line therapy, should be biopsied.

VSCC arises from precursor lesions or high-grade vulvar intraepithelial neoplasia (VIN). The 2015 International Society for the Study of Vulvovaginal Disease nomenclature classifies high-grade VIN into high-grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN). Most patients with high-grade VIN are diagnosed with HSIL or usual type VIN. A preponderance of these lesions (75%-85%) are HPV positive, predominantly HPV 16. Vulvar HSIL (vHSIL) lesions affect younger women. The lesions tend to be multifocal and extensive. On the other hand, dVIN typically affects older women and commonly develops as a solitary lesion. While dVIN accounts for only a small subset of patients with high-grade VIN, these lesions are HPV negative and associated with lichen sclerosus.

Both disease entities, vHSIL and dVIN, are increasing in incidence. There is a higher risk and shortened period of progression to cancer in patients with dVIN compared to HSIL. The cancer risk of vHSIL is relatively low. The 10-year cumulative VSCC risk reported in the literature is 10.3%; 9.7% for vHSIL and 50% for dVIN. Patients with vHSIL could benefit from less aggressive treatment modalities.

Dr. Jackson-Moore is associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the university.
 

References

Cendejas BR et al. Am J Obstet Gynecol. 2015 Mar;212(3):291-7.

Lebreton M et al. J Gynecol Obstet Hum Reprod. 2020 Nov;49(9):101801.

Thuijs NB et al. Int J Cancer. 2021 Jan 1;148(1):90-8. doi: 10.1002/ijc.33198. .

Trutnovsky G et al. Lancet. 2022 May 7;399(10337):1790-8. Erratum in: Lancet. 2022 Oct 8;400(10359):1194.

Vulvar squamous cell carcinomas (VSCC) comprise approximately 90% of all vulvar malignancies. Unlike cervical SCC, which are predominantly human papilloma virus (HPV) positive, only a minority of VSCC are HPV positive – on the order of 15%-25% of cases. Most cases occur in the setting of lichen sclerosus and are HPV negative.

Lichen sclerosus is a chronic inflammatory dermatitis typically involving the anogenital area, which in some cases can become seriously distorted (e.g. atrophy of the labia minora, clitoral phimosis, and introital stenosis). Although most cases are diagnosed in postmenopausal women, LS can affect women of any age. The true prevalence of lichen sclerosus is unknown. Recent studies have shown a prevalence of 1 in 60; among older women, it can even be as high as 1 in 30. While lichen sclerosus is a pruriginous condition, it is often asymptomatic. It is not considered a premalignant condition. The diagnosis is clinical; however, suspicious lesions (erosions/ulcerations, hyperkeratosis, pigmented areas, ecchymosis, warty or papular lesions), particularly when recalcitrant to adequate first-line therapy, should be biopsied.

VSCC arises from precursor lesions or high-grade vulvar intraepithelial neoplasia (VIN). The 2015 International Society for the Study of Vulvovaginal Disease nomenclature classifies high-grade VIN into high-grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN). Most patients with high-grade VIN are diagnosed with HSIL or usual type VIN. A preponderance of these lesions (75%-85%) are HPV positive, predominantly HPV 16. Vulvar HSIL (vHSIL) lesions affect younger women. The lesions tend to be multifocal and extensive. On the other hand, dVIN typically affects older women and commonly develops as a solitary lesion. While dVIN accounts for only a small subset of patients with high-grade VIN, these lesions are HPV negative and associated with lichen sclerosus.

Both disease entities, vHSIL and dVIN, are increasing in incidence. There is a higher risk and shortened period of progression to cancer in patients with dVIN compared to HSIL. The cancer risk of vHSIL is relatively low. The 10-year cumulative VSCC risk reported in the literature is 10.3%; 9.7% for vHSIL and 50% for dVIN. Patients with vHSIL could benefit from less aggressive treatment modalities.

Dr. Jackson-Moore is associate professor in gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the university.
 

References

Cendejas BR et al. Am J Obstet Gynecol. 2015 Mar;212(3):291-7.

Lebreton M et al. J Gynecol Obstet Hum Reprod. 2020 Nov;49(9):101801.

Thuijs NB et al. Int J Cancer. 2021 Jan 1;148(1):90-8. doi: 10.1002/ijc.33198. .

Trutnovsky G et al. Lancet. 2022 May 7;399(10337):1790-8. Erratum in: Lancet. 2022 Oct 8;400(10359):1194.

From the Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Clinical inertia is defined as the failure of clinicians to initiate or escalate guideline-directed medical therapy to achieve treatment goals for well-defined clinical conditions.^1,2 Evidence-based guidelines recommend optimal disease management with readily available medical therapies throughout the phases of clinical care. Unfortunately, the care provided to individual patients undergoes multiple modifications throughout the disease course, resulting in divergent pathways, significant deviations from treatment guidelines, and failure of “safeguard” checkpoints to reinstate, initiate, optimize, or stop treatments. Clinical inertia generally describes rigidity or resistance to change around implementing evidence-based guidelines. Furthermore, this term describes treatment behavior on the part of an individual clinician, not organizational inertia, which generally encompasses both internal (immediate clinical practice settings) and external factors (national and international guidelines and recommendations), eventually leading to resistance to optimizing disease treatment and therapeutic regimens. Individual clinicians’ clinical inertia in the form of resistance to guideline implementation and evidence-based principles can be one factor that drives organizational inertia. In turn, such individual behavior can be dictated by personal beliefs, knowledge, interpretation, skills, management principles, and biases. The terms therapeutic inertia or clinical inertia should not be confused with nonadherence from the patient’s standpoint when the clinician follows the best practice guidelines.³

Clinical inertia has been described in several clinical domains, including diabetes,^4,5 hypertension,^6,7 heart failure,⁸ depression,⁹ pulmonary medicine,¹⁰ and complex disease management.¹¹ Clinicians can set suboptimal treatment goals due to specific beliefs and attitudes around optimal therapeutic goals. For example, when treating a patient with a chronic disease that is presently stable, a clinician could elect to initiate suboptimal treatment, as escalation of treatment might not be the priority in stable disease; they also may have concerns about overtreatment. Other factors that can contribute to clinical inertia (ie, undertreatment in the presence of indications for treatment) include those related to the patient, the clinical setting, and the organization, along with the importance of individualizing therapies in specific patients. Organizational inertia is the initial global resistance by the system to implementation, which can slow the dissemination and adaptation of best practices but eventually declines over time. Individual clinical inertia, on the other hand, will likely persist after the system-level rollout of guideline-based approaches.

The trajectory of dissemination, implementation, and adaptation of innovations and best practices is illustrated in the Figure. When the guidelines and medical societies endorse the adaptation of innovations or practice change after the benefits of such innovations/change have been established by the regulatory bodies, uptake can be hindered by both organizational and clinical inertia. Overcoming inertia to system-level changes requires addressing individual clinicians, along with practice and organizational factors, in order to ensure systematic adaptations. From the clinicians’ view, training and cognitive interventions to improve the adaptation and coping skills can improve understanding of treatment options through standardized educational and behavioral modification tools, direct and indirect feedback around performance, and decision support through a continuous improvement approach on both individual and system levels.

Addressing inertia in clinical practice requires a deep understanding of the individual and organizational elements that foster resistance to adapting best practice models. Research that explores tools and approaches to overcome inertia in managing complex diseases is a key step in advancing clinical innovation and disseminating best practices.

Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]

Disclosures: None reported.

From the Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Clinical inertia is defined as the failure of clinicians to initiate or escalate guideline-directed medical therapy to achieve treatment goals for well-defined clinical conditions.^1,2 Evidence-based guidelines recommend optimal disease management with readily available medical therapies throughout the phases of clinical care. Unfortunately, the care provided to individual patients undergoes multiple modifications throughout the disease course, resulting in divergent pathways, significant deviations from treatment guidelines, and failure of “safeguard” checkpoints to reinstate, initiate, optimize, or stop treatments. Clinical inertia generally describes rigidity or resistance to change around implementing evidence-based guidelines. Furthermore, this term describes treatment behavior on the part of an individual clinician, not organizational inertia, which generally encompasses both internal (immediate clinical practice settings) and external factors (national and international guidelines and recommendations), eventually leading to resistance to optimizing disease treatment and therapeutic regimens. Individual clinicians’ clinical inertia in the form of resistance to guideline implementation and evidence-based principles can be one factor that drives organizational inertia. In turn, such individual behavior can be dictated by personal beliefs, knowledge, interpretation, skills, management principles, and biases. The terms therapeutic inertia or clinical inertia should not be confused with nonadherence from the patient’s standpoint when the clinician follows the best practice guidelines.³

Clinical inertia has been described in several clinical domains, including diabetes,^4,5 hypertension,^6,7 heart failure,⁸ depression,⁹ pulmonary medicine,¹⁰ and complex disease management.¹¹ Clinicians can set suboptimal treatment goals due to specific beliefs and attitudes around optimal therapeutic goals. For example, when treating a patient with a chronic disease that is presently stable, a clinician could elect to initiate suboptimal treatment, as escalation of treatment might not be the priority in stable disease; they also may have concerns about overtreatment. Other factors that can contribute to clinical inertia (ie, undertreatment in the presence of indications for treatment) include those related to the patient, the clinical setting, and the organization, along with the importance of individualizing therapies in specific patients. Organizational inertia is the initial global resistance by the system to implementation, which can slow the dissemination and adaptation of best practices but eventually declines over time. Individual clinical inertia, on the other hand, will likely persist after the system-level rollout of guideline-based approaches.

The trajectory of dissemination, implementation, and adaptation of innovations and best practices is illustrated in the Figure. When the guidelines and medical societies endorse the adaptation of innovations or practice change after the benefits of such innovations/change have been established by the regulatory bodies, uptake can be hindered by both organizational and clinical inertia. Overcoming inertia to system-level changes requires addressing individual clinicians, along with practice and organizational factors, in order to ensure systematic adaptations. From the clinicians’ view, training and cognitive interventions to improve the adaptation and coping skills can improve understanding of treatment options through standardized educational and behavioral modification tools, direct and indirect feedback around performance, and decision support through a continuous improvement approach on both individual and system levels.

Addressing inertia in clinical practice requires a deep understanding of the individual and organizational elements that foster resistance to adapting best practice models. Research that explores tools and approaches to overcome inertia in managing complex diseases is a key step in advancing clinical innovation and disseminating best practices.

Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]

Disclosures: None reported.

From the Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Clinical inertia is defined as the failure of clinicians to initiate or escalate guideline-directed medical therapy to achieve treatment goals for well-defined clinical conditions.^1,2 Evidence-based guidelines recommend optimal disease management with readily available medical therapies throughout the phases of clinical care. Unfortunately, the care provided to individual patients undergoes multiple modifications throughout the disease course, resulting in divergent pathways, significant deviations from treatment guidelines, and failure of “safeguard” checkpoints to reinstate, initiate, optimize, or stop treatments. Clinical inertia generally describes rigidity or resistance to change around implementing evidence-based guidelines. Furthermore, this term describes treatment behavior on the part of an individual clinician, not organizational inertia, which generally encompasses both internal (immediate clinical practice settings) and external factors (national and international guidelines and recommendations), eventually leading to resistance to optimizing disease treatment and therapeutic regimens. Individual clinicians’ clinical inertia in the form of resistance to guideline implementation and evidence-based principles can be one factor that drives organizational inertia. In turn, such individual behavior can be dictated by personal beliefs, knowledge, interpretation, skills, management principles, and biases. The terms therapeutic inertia or clinical inertia should not be confused with nonadherence from the patient’s standpoint when the clinician follows the best practice guidelines.³

Clinical inertia has been described in several clinical domains, including diabetes,^4,5 hypertension,^6,7 heart failure,⁸ depression,⁹ pulmonary medicine,¹⁰ and complex disease management.¹¹ Clinicians can set suboptimal treatment goals due to specific beliefs and attitudes around optimal therapeutic goals. For example, when treating a patient with a chronic disease that is presently stable, a clinician could elect to initiate suboptimal treatment, as escalation of treatment might not be the priority in stable disease; they also may have concerns about overtreatment. Other factors that can contribute to clinical inertia (ie, undertreatment in the presence of indications for treatment) include those related to the patient, the clinical setting, and the organization, along with the importance of individualizing therapies in specific patients. Organizational inertia is the initial global resistance by the system to implementation, which can slow the dissemination and adaptation of best practices but eventually declines over time. Individual clinical inertia, on the other hand, will likely persist after the system-level rollout of guideline-based approaches.

The trajectory of dissemination, implementation, and adaptation of innovations and best practices is illustrated in the Figure. When the guidelines and medical societies endorse the adaptation of innovations or practice change after the benefits of such innovations/change have been established by the regulatory bodies, uptake can be hindered by both organizational and clinical inertia. Overcoming inertia to system-level changes requires addressing individual clinicians, along with practice and organizational factors, in order to ensure systematic adaptations. From the clinicians’ view, training and cognitive interventions to improve the adaptation and coping skills can improve understanding of treatment options through standardized educational and behavioral modification tools, direct and indirect feedback around performance, and decision support through a continuous improvement approach on both individual and system levels.

Addressing inertia in clinical practice requires a deep understanding of the individual and organizational elements that foster resistance to adapting best practice models. Research that explores tools and approaches to overcome inertia in managing complex diseases is a key step in advancing clinical innovation and disseminating best practices.

Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]

Disclosures: None reported.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

In a recent column, I cautiously discussed what has been called gender-affirming or transgender care.

In the days following the appearance of that Letters From Maine column on this topic, I received an unusual number of responses from readers suggesting I had touched on a topic that was on the minds of many pediatricians.

Since then, the Florida Board of Medicine and Osteopathic Medicine voted to forbid physicians from prescribing puberty blockers and hormones and/or performing surgeries in patients under age 18 who were seeking transgender care. Children already receiving treatments were exempt from the ruling. The osteopathic board added a second exception in cases where the child was a participant in a research protocol. The board of medicine inexplicably did not include this exception.

Regardless of how one feels about the ethics and the appropriateness of transgender care, it is not an issue to be decided by a politically appointed entity.

As I look back over what I have learned by watching this tragic drama play out, I am struck by a distinction that has yet to receive enough attention. When we are discussing gender dysphoria we are really talking about two different pediatric populations and scenarios. There is the child who from a very young age has consistently preferred to dress and behave in a manner that is different from the gender he or she was assigned at birth. The management of this child is a challenge that requires a careful balance of support and protection from the harsh realities of the gender-regimented world.

The second scenario stars the adolescent who has no prior history of gender dysphoria, or at least no outward manifestations. Then, faced by the challenges of puberty and adolescence, something or things happen that erupt into a full-blown gender-dysphoric storm. We currently have very little understanding of what those “things” are.

Each population can probably be further divided into subgroups – and that’s just the point. Every gender-dysphoric child, whether their dysphoria began at age 2 or 12, is an individual with a unique family dynamic and socioeconomic background. They may share some as yet unknown genetic signature, but in our current state of ignorance they deserve, as do all of our patients, to be treated as individuals by their primary care physicians and consultants who must at first do no harm. One size does not fit all and certainly their care should not be dictated by a politically influenced entity.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent column, I cautiously discussed what has been called gender-affirming or transgender care.

In the days following the appearance of that Letters From Maine column on this topic, I received an unusual number of responses from readers suggesting I had touched on a topic that was on the minds of many pediatricians.

Since then, the Florida Board of Medicine and Osteopathic Medicine voted to forbid physicians from prescribing puberty blockers and hormones and/or performing surgeries in patients under age 18 who were seeking transgender care. Children already receiving treatments were exempt from the ruling. The osteopathic board added a second exception in cases where the child was a participant in a research protocol. The board of medicine inexplicably did not include this exception.

Regardless of how one feels about the ethics and the appropriateness of transgender care, it is not an issue to be decided by a politically appointed entity.

As I look back over what I have learned by watching this tragic drama play out, I am struck by a distinction that has yet to receive enough attention. When we are discussing gender dysphoria we are really talking about two different pediatric populations and scenarios. There is the child who from a very young age has consistently preferred to dress and behave in a manner that is different from the gender he or she was assigned at birth. The management of this child is a challenge that requires a careful balance of support and protection from the harsh realities of the gender-regimented world.

The second scenario stars the adolescent who has no prior history of gender dysphoria, or at least no outward manifestations. Then, faced by the challenges of puberty and adolescence, something or things happen that erupt into a full-blown gender-dysphoric storm. We currently have very little understanding of what those “things” are.

Each population can probably be further divided into subgroups – and that’s just the point. Every gender-dysphoric child, whether their dysphoria began at age 2 or 12, is an individual with a unique family dynamic and socioeconomic background. They may share some as yet unknown genetic signature, but in our current state of ignorance they deserve, as do all of our patients, to be treated as individuals by their primary care physicians and consultants who must at first do no harm. One size does not fit all and certainly their care should not be dictated by a politically influenced entity.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a recent column, I cautiously discussed what has been called gender-affirming or transgender care.

In the days following the appearance of that Letters From Maine column on this topic, I received an unusual number of responses from readers suggesting I had touched on a topic that was on the minds of many pediatricians.

Since then, the Florida Board of Medicine and Osteopathic Medicine voted to forbid physicians from prescribing puberty blockers and hormones and/or performing surgeries in patients under age 18 who were seeking transgender care. Children already receiving treatments were exempt from the ruling. The osteopathic board added a second exception in cases where the child was a participant in a research protocol. The board of medicine inexplicably did not include this exception.

Regardless of how one feels about the ethics and the appropriateness of transgender care, it is not an issue to be decided by a politically appointed entity.

As I look back over what I have learned by watching this tragic drama play out, I am struck by a distinction that has yet to receive enough attention. When we are discussing gender dysphoria we are really talking about two different pediatric populations and scenarios. There is the child who from a very young age has consistently preferred to dress and behave in a manner that is different from the gender he or she was assigned at birth. The management of this child is a challenge that requires a careful balance of support and protection from the harsh realities of the gender-regimented world.

The second scenario stars the adolescent who has no prior history of gender dysphoria, or at least no outward manifestations. Then, faced by the challenges of puberty and adolescence, something or things happen that erupt into a full-blown gender-dysphoric storm. We currently have very little understanding of what those “things” are.

Each population can probably be further divided into subgroups – and that’s just the point. Every gender-dysphoric child, whether their dysphoria began at age 2 or 12, is an individual with a unique family dynamic and socioeconomic background. They may share some as yet unknown genetic signature, but in our current state of ignorance they deserve, as do all of our patients, to be treated as individuals by their primary care physicians and consultants who must at first do no harm. One size does not fit all and certainly their care should not be dictated by a politically influenced entity.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Meditation has become a popular practice in the United States over the last decade. It is not limited to adults, but can be learned and practiced by children and teenagers also. Variants are being used in many schools as parts of a social and emotional learning curriculum, and different kinds of mindfulness practices are common parts of psychological treatments. In this month’s column, we will review the evidence that supports the efficacy of a meditation practice to treat the mental health problems that are common in children and adolescents, and review how it might be a useful adjunct to the screening, education, and treatments that you offer your young patients.

There are many different types of meditation practices, but the unifying feature is known as mindfulness. Most broadly, mindfulness refers to a state of nonjudgmental awareness of one’s thoughts, feelings, or sensations. A mindfulness meditation practice involves physical stillness and focused attention, typically on the physical sensations of one’s breath. When thoughts, feelings, or physical sensations intrude on the stillness, one learns to cultivate a nonjudgmental awareness of those experiences without disrupting the state of quiet concentration. It could be said that meditation is easy to learn and difficult to master, and that is why it should be practiced regularly. Part of its growing popularity has undoubtedly been served by the ease with which people can access a variety of guided meditations (through apps, YouTube, and beyond) that make it relatively easy to access a variety of methods to learn how to practice mindfulness meditation.

The benefits of meditation in adults are well-established, including lower blood pressure, lower rates of heart disease, lower markers of inflammation, better sleep, and self-described levels of well-being. Meditation appears to be especially effective at mitigating the cardiovascular, metabolic, autoimmune, and inflammatory consequences of high-stress or unhealthy lifestyles in adults. Children and adolescents typically do not suffer from these diseases, but there is growing evidence that mindfulness practices can improve self-reported stress management skills, well-being, and sleep in young people; skills that can protect their physical and mental health. In addition, there is some evidence that mindfulness can be effective as a treatment for the common psychiatric illnesses of youth.
 

Anxiety

There is robust evidence for the efficacy of mindfulness-based interventions (including a regular mindfulness meditation practice) in the treatment of anxiety disorders in youth. Multiple studies and meta-analyses have demonstrated significant and sustained improvement in anxiety symptoms in these young patients. This makes sense when one considers that most psychotherapy treatments for anxiety include the cultivation of self-awareness and the ability to recognize the feelings of anxiety. This is critical as youth with anxiety disorders often mistake these feelings for facts. The treatment then shifts toward practice tolerating these feelings to help children develop an appreciation that they can face and manage anxiety and that it does not need to be avoided. Part of tolerating these feelings includes building skills to facilitate calm and physical relaxation in the face of these anxious feelings.

This is the core of exposure-based psychotherapies. Mindfulness practices echo the cultivation of self-awareness with focus and physical calm. Studies have shown that mindfulness-based interventions have significant and lasting effects on the symptoms of anxiety disorders in youth, including those youth with comorbid ADHD and learning disabilities. It is important to be aware that, for youth who have experienced trauma, mindfulness meditation can trigger a flood of re-experiencing phenomena, and it is important that those youth also are receiving treatment for PTSD.
 

Depression

There is evidence that some of the symptoms that occur as part of depression in adolescents improve with mindfulness-based interventions. In particular, symptoms of anger, irritability, disruptive behaviors, suicidality, and even impulsive self-injury improve with mindfulness-based interventions. Dialectical behavioral therapy (DBT) and acceptance and commitment therapy (ACT) have the nonjudgmental self-awareness of mindfulness built in as a component of the therapy. But mindfulness practices without explicit cognitive and behavioral components of psychotherapy for depression are not effective as stand-alone treatment of major depressive disorder in youth.

Multiple meta-analyses have demonstrated that stimulant treatment is more effective than behavioral or environmental interventions in the treatment of ADHD in children and adolescents, and combined treatments have not shown substantial additional improvement over medications alone in randomized controlled studies. But there is a lot of interest in finding effective treatments beyond medications that will help children with ADHD build important cognitive and behavioral skills that may lag developmentally.

Now there is an emerging body of evidence indicating that mindfulness skills in children with ADHD are quite effective for improving their sustained attention, social skills, behavioral control, and even hyperactivity. Additionally, methods to teach mindfulness skills to children who struggle with stillness and focused attention have been developed for these studies (“mindful martial arts”). Again, this intervention has not yet shown the same level of efficacy as medication treatments for ADHD symptoms, but it has demonstrated promise in early trials. Interestingly, it has also shown promise as a component of parenting interventions for youth with ADHD.

You do not need to wait for decisive evidence from randomized controlled trials to recommend mindfulness training for your patients with anxiety, ADHD, or even depression. Indeed, this practice alone may be adequate as a treatment for mild to moderate anxiety disorders. But you can also recommend it as an empowering and effective adjunctive treatment for almost every psychiatric illness and subclinical syndrome, and one that is affordable and easy for families to access. It would be valuable for you to recommend that your patients and their parents both try a mindfulness practice alongside your recommendations about healthy sleep, exercise, and nutrition. There are free apps such as Smiling Mind, Sound Mind, and Thrive Global that families can try together. Some children may need to move physically to be able to practice mindfulness, so yoga or walking meditations can be a better practice for them. When parents can try mindfulness practice alongside their children, it will facilitate their child’s efforts to develop these skills, and the improved sleep, focus, and stress management skills in parents can make a significant difference in the health and well-being of the whole family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Meditation has become a popular practice in the United States over the last decade. It is not limited to adults, but can be learned and practiced by children and teenagers also. Variants are being used in many schools as parts of a social and emotional learning curriculum, and different kinds of mindfulness practices are common parts of psychological treatments. In this month’s column, we will review the evidence that supports the efficacy of a meditation practice to treat the mental health problems that are common in children and adolescents, and review how it might be a useful adjunct to the screening, education, and treatments that you offer your young patients.

There are many different types of meditation practices, but the unifying feature is known as mindfulness. Most broadly, mindfulness refers to a state of nonjudgmental awareness of one’s thoughts, feelings, or sensations. A mindfulness meditation practice involves physical stillness and focused attention, typically on the physical sensations of one’s breath. When thoughts, feelings, or physical sensations intrude on the stillness, one learns to cultivate a nonjudgmental awareness of those experiences without disrupting the state of quiet concentration. It could be said that meditation is easy to learn and difficult to master, and that is why it should be practiced regularly. Part of its growing popularity has undoubtedly been served by the ease with which people can access a variety of guided meditations (through apps, YouTube, and beyond) that make it relatively easy to access a variety of methods to learn how to practice mindfulness meditation.

The benefits of meditation in adults are well-established, including lower blood pressure, lower rates of heart disease, lower markers of inflammation, better sleep, and self-described levels of well-being. Meditation appears to be especially effective at mitigating the cardiovascular, metabolic, autoimmune, and inflammatory consequences of high-stress or unhealthy lifestyles in adults. Children and adolescents typically do not suffer from these diseases, but there is growing evidence that mindfulness practices can improve self-reported stress management skills, well-being, and sleep in young people; skills that can protect their physical and mental health. In addition, there is some evidence that mindfulness can be effective as a treatment for the common psychiatric illnesses of youth.
 

Anxiety

There is robust evidence for the efficacy of mindfulness-based interventions (including a regular mindfulness meditation practice) in the treatment of anxiety disorders in youth. Multiple studies and meta-analyses have demonstrated significant and sustained improvement in anxiety symptoms in these young patients. This makes sense when one considers that most psychotherapy treatments for anxiety include the cultivation of self-awareness and the ability to recognize the feelings of anxiety. This is critical as youth with anxiety disorders often mistake these feelings for facts. The treatment then shifts toward practice tolerating these feelings to help children develop an appreciation that they can face and manage anxiety and that it does not need to be avoided. Part of tolerating these feelings includes building skills to facilitate calm and physical relaxation in the face of these anxious feelings.

This is the core of exposure-based psychotherapies. Mindfulness practices echo the cultivation of self-awareness with focus and physical calm. Studies have shown that mindfulness-based interventions have significant and lasting effects on the symptoms of anxiety disorders in youth, including those youth with comorbid ADHD and learning disabilities. It is important to be aware that, for youth who have experienced trauma, mindfulness meditation can trigger a flood of re-experiencing phenomena, and it is important that those youth also are receiving treatment for PTSD.
 

Depression

There is evidence that some of the symptoms that occur as part of depression in adolescents improve with mindfulness-based interventions. In particular, symptoms of anger, irritability, disruptive behaviors, suicidality, and even impulsive self-injury improve with mindfulness-based interventions. Dialectical behavioral therapy (DBT) and acceptance and commitment therapy (ACT) have the nonjudgmental self-awareness of mindfulness built in as a component of the therapy. But mindfulness practices without explicit cognitive and behavioral components of psychotherapy for depression are not effective as stand-alone treatment of major depressive disorder in youth.

Multiple meta-analyses have demonstrated that stimulant treatment is more effective than behavioral or environmental interventions in the treatment of ADHD in children and adolescents, and combined treatments have not shown substantial additional improvement over medications alone in randomized controlled studies. But there is a lot of interest in finding effective treatments beyond medications that will help children with ADHD build important cognitive and behavioral skills that may lag developmentally.

Now there is an emerging body of evidence indicating that mindfulness skills in children with ADHD are quite effective for improving their sustained attention, social skills, behavioral control, and even hyperactivity. Additionally, methods to teach mindfulness skills to children who struggle with stillness and focused attention have been developed for these studies (“mindful martial arts”). Again, this intervention has not yet shown the same level of efficacy as medication treatments for ADHD symptoms, but it has demonstrated promise in early trials. Interestingly, it has also shown promise as a component of parenting interventions for youth with ADHD.

You do not need to wait for decisive evidence from randomized controlled trials to recommend mindfulness training for your patients with anxiety, ADHD, or even depression. Indeed, this practice alone may be adequate as a treatment for mild to moderate anxiety disorders. But you can also recommend it as an empowering and effective adjunctive treatment for almost every psychiatric illness and subclinical syndrome, and one that is affordable and easy for families to access. It would be valuable for you to recommend that your patients and their parents both try a mindfulness practice alongside your recommendations about healthy sleep, exercise, and nutrition. There are free apps such as Smiling Mind, Sound Mind, and Thrive Global that families can try together. Some children may need to move physically to be able to practice mindfulness, so yoga or walking meditations can be a better practice for them. When parents can try mindfulness practice alongside their children, it will facilitate their child’s efforts to develop these skills, and the improved sleep, focus, and stress management skills in parents can make a significant difference in the health and well-being of the whole family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Meditation has become a popular practice in the United States over the last decade. It is not limited to adults, but can be learned and practiced by children and teenagers also. Variants are being used in many schools as parts of a social and emotional learning curriculum, and different kinds of mindfulness practices are common parts of psychological treatments. In this month’s column, we will review the evidence that supports the efficacy of a meditation practice to treat the mental health problems that are common in children and adolescents, and review how it might be a useful adjunct to the screening, education, and treatments that you offer your young patients.

There are many different types of meditation practices, but the unifying feature is known as mindfulness. Most broadly, mindfulness refers to a state of nonjudgmental awareness of one’s thoughts, feelings, or sensations. A mindfulness meditation practice involves physical stillness and focused attention, typically on the physical sensations of one’s breath. When thoughts, feelings, or physical sensations intrude on the stillness, one learns to cultivate a nonjudgmental awareness of those experiences without disrupting the state of quiet concentration. It could be said that meditation is easy to learn and difficult to master, and that is why it should be practiced regularly. Part of its growing popularity has undoubtedly been served by the ease with which people can access a variety of guided meditations (through apps, YouTube, and beyond) that make it relatively easy to access a variety of methods to learn how to practice mindfulness meditation.

The benefits of meditation in adults are well-established, including lower blood pressure, lower rates of heart disease, lower markers of inflammation, better sleep, and self-described levels of well-being. Meditation appears to be especially effective at mitigating the cardiovascular, metabolic, autoimmune, and inflammatory consequences of high-stress or unhealthy lifestyles in adults. Children and adolescents typically do not suffer from these diseases, but there is growing evidence that mindfulness practices can improve self-reported stress management skills, well-being, and sleep in young people; skills that can protect their physical and mental health. In addition, there is some evidence that mindfulness can be effective as a treatment for the common psychiatric illnesses of youth.
 

Anxiety

There is robust evidence for the efficacy of mindfulness-based interventions (including a regular mindfulness meditation practice) in the treatment of anxiety disorders in youth. Multiple studies and meta-analyses have demonstrated significant and sustained improvement in anxiety symptoms in these young patients. This makes sense when one considers that most psychotherapy treatments for anxiety include the cultivation of self-awareness and the ability to recognize the feelings of anxiety. This is critical as youth with anxiety disorders often mistake these feelings for facts. The treatment then shifts toward practice tolerating these feelings to help children develop an appreciation that they can face and manage anxiety and that it does not need to be avoided. Part of tolerating these feelings includes building skills to facilitate calm and physical relaxation in the face of these anxious feelings.

This is the core of exposure-based psychotherapies. Mindfulness practices echo the cultivation of self-awareness with focus and physical calm. Studies have shown that mindfulness-based interventions have significant and lasting effects on the symptoms of anxiety disorders in youth, including those youth with comorbid ADHD and learning disabilities. It is important to be aware that, for youth who have experienced trauma, mindfulness meditation can trigger a flood of re-experiencing phenomena, and it is important that those youth also are receiving treatment for PTSD.
 

Depression

There is evidence that some of the symptoms that occur as part of depression in adolescents improve with mindfulness-based interventions. In particular, symptoms of anger, irritability, disruptive behaviors, suicidality, and even impulsive self-injury improve with mindfulness-based interventions. Dialectical behavioral therapy (DBT) and acceptance and commitment therapy (ACT) have the nonjudgmental self-awareness of mindfulness built in as a component of the therapy. But mindfulness practices without explicit cognitive and behavioral components of psychotherapy for depression are not effective as stand-alone treatment of major depressive disorder in youth.

Multiple meta-analyses have demonstrated that stimulant treatment is more effective than behavioral or environmental interventions in the treatment of ADHD in children and adolescents, and combined treatments have not shown substantial additional improvement over medications alone in randomized controlled studies. But there is a lot of interest in finding effective treatments beyond medications that will help children with ADHD build important cognitive and behavioral skills that may lag developmentally.

Now there is an emerging body of evidence indicating that mindfulness skills in children with ADHD are quite effective for improving their sustained attention, social skills, behavioral control, and even hyperactivity. Additionally, methods to teach mindfulness skills to children who struggle with stillness and focused attention have been developed for these studies (“mindful martial arts”). Again, this intervention has not yet shown the same level of efficacy as medication treatments for ADHD symptoms, but it has demonstrated promise in early trials. Interestingly, it has also shown promise as a component of parenting interventions for youth with ADHD.

You do not need to wait for decisive evidence from randomized controlled trials to recommend mindfulness training for your patients with anxiety, ADHD, or even depression. Indeed, this practice alone may be adequate as a treatment for mild to moderate anxiety disorders. But you can also recommend it as an empowering and effective adjunctive treatment for almost every psychiatric illness and subclinical syndrome, and one that is affordable and easy for families to access. It would be valuable for you to recommend that your patients and their parents both try a mindfulness practice alongside your recommendations about healthy sleep, exercise, and nutrition. There are free apps such as Smiling Mind, Sound Mind, and Thrive Global that families can try together. Some children may need to move physically to be able to practice mindfulness, so yoga or walking meditations can be a better practice for them. When parents can try mindfulness practice alongside their children, it will facilitate their child’s efforts to develop these skills, and the improved sleep, focus, and stress management skills in parents can make a significant difference in the health and well-being of the whole family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Dear Colleagues,

We have a mismatch. The evidence supporting treatment for Paxlovid is compelling for people aged 60 or over, but the older patients in the United States are much less likely to be treated. Not only was there a randomized, placebo-controlled trial of high-risk patients which showed 89% reduction of hospitalizations and deaths (median age, 45), but there have been multiple real-world effectiveness studies subsequently published that have partitioned the benefit for age 65 or older, such as the ones from Israel and Hong Kong (age 60+). Overall, the real-world effectiveness in the first month after treatment is at least as good, if not better, than in the high-risk randomized trial.

But it’s more likely in the United States for a person age 45-50 to get Paxlovid over people age 80 or older. Why? We’re doing the current survey to find out, but the most likely reasons include (1) lack of confidence of benefit; (2) medication interactions; and (3) concerns over rebound.

Let me address each of these briefly. The lack of confidence in benefit stems from the fact that the initial high-risk trial was in unvaccinated individuals. That concern can now be put aside because all of the several real-world studies confirming the protective benefit against hospitalizations and deaths are in people who have been vaccinated, and a significant proportion received booster shots.

The potential medication interactions due to the ritonavir component of the Paxlovid drug combination, attributable to its cytochrome P450 3A4 inhibition, have been unduly emphasized. There are many drug-interaction checkers for Paxlovid, but this one from the University of Liverpool is user friendly, color- and icon-coded, and shows that the vast majority of interactions can be sidestepped by discontinuing the medication of concern for the length of the Paxlovid treatment, 5 days. The simple chart is provided in my recent substack newsletter.

As far as rebound, this problem has unfortunately been exaggerated because of lack of prospective systematic studies and appreciation that a positive test of clinical symptom rebound can occur without Paxlovid. There are soon to be multiple reports that the incidence of Paxlovid rebound is fairly low, in the range of 10%. That concern should not be a reason to withhold treatment.

Now the plot thickens. A new preprint report from the Veterans Health Administration, the largest health care system in the United States, looks at 90-day outcomes of about 9,000 Paxlovid-treated patients and approximately 47,000 controls. Not only was there a 26% reduction in long COVID, but of the breakdown of 12 organs/systems and symptoms, 10 of 12 were significantly reduced with Paxlovid, including pulmonary embolism, deep vein thrombosis, and neurocognitive impairment. There was also a 48% reduction in death and a 30% reduction in hospitalizations after the first 30 days. I have reviewed all of these data and put them in context in a recent newsletter. A key point is that the magnitude of benefit was unaffected by vaccination or booster status, or prior COVID infections, or unvaccinated status. Also, it was the same for men and women, as well as for age > 70 and age < 60. These findings all emphasize a new reason to be using Paxlovid therapy, and if replicated, Paxlovid may even be indicated for younger patients (who are at low risk for hospitalizations and deaths but at increased risk for long COVID).

In summary, for older patients, we should be thinking of why we should be using Paxlovid rather than the reason not to treat. We’ll be interested in the survey results to understand the mismatch better, and we look forward to your ideas and feedback to make better use of this treatment for the people who need it the most.

Sincerely yours, Eric J. Topol, MD

Dr. Topol reports no conflicts of interest with Pfizer; he receives no honoraria or speaker fees, does not serve in an advisory role, and has no financial association with the company.

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

Dear Colleagues,

We have a mismatch. The evidence supporting treatment for Paxlovid is compelling for people aged 60 or over, but the older patients in the United States are much less likely to be treated. Not only was there a randomized, placebo-controlled trial of high-risk patients which showed 89% reduction of hospitalizations and deaths (median age, 45), but there have been multiple real-world effectiveness studies subsequently published that have partitioned the benefit for age 65 or older, such as the ones from Israel and Hong Kong (age 60+). Overall, the real-world effectiveness in the first month after treatment is at least as good, if not better, than in the high-risk randomized trial.

But it’s more likely in the United States for a person age 45-50 to get Paxlovid over people age 80 or older. Why? We’re doing the current survey to find out, but the most likely reasons include (1) lack of confidence of benefit; (2) medication interactions; and (3) concerns over rebound.

Let me address each of these briefly. The lack of confidence in benefit stems from the fact that the initial high-risk trial was in unvaccinated individuals. That concern can now be put aside because all of the several real-world studies confirming the protective benefit against hospitalizations and deaths are in people who have been vaccinated, and a significant proportion received booster shots.

The potential medication interactions due to the ritonavir component of the Paxlovid drug combination, attributable to its cytochrome P450 3A4 inhibition, have been unduly emphasized. There are many drug-interaction checkers for Paxlovid, but this one from the University of Liverpool is user friendly, color- and icon-coded, and shows that the vast majority of interactions can be sidestepped by discontinuing the medication of concern for the length of the Paxlovid treatment, 5 days. The simple chart is provided in my recent substack newsletter.

As far as rebound, this problem has unfortunately been exaggerated because of lack of prospective systematic studies and appreciation that a positive test of clinical symptom rebound can occur without Paxlovid. There are soon to be multiple reports that the incidence of Paxlovid rebound is fairly low, in the range of 10%. That concern should not be a reason to withhold treatment.

Now the plot thickens. A new preprint report from the Veterans Health Administration, the largest health care system in the United States, looks at 90-day outcomes of about 9,000 Paxlovid-treated patients and approximately 47,000 controls. Not only was there a 26% reduction in long COVID, but of the breakdown of 12 organs/systems and symptoms, 10 of 12 were significantly reduced with Paxlovid, including pulmonary embolism, deep vein thrombosis, and neurocognitive impairment. There was also a 48% reduction in death and a 30% reduction in hospitalizations after the first 30 days. I have reviewed all of these data and put them in context in a recent newsletter. A key point is that the magnitude of benefit was unaffected by vaccination or booster status, or prior COVID infections, or unvaccinated status. Also, it was the same for men and women, as well as for age > 70 and age < 60. These findings all emphasize a new reason to be using Paxlovid therapy, and if replicated, Paxlovid may even be indicated for younger patients (who are at low risk for hospitalizations and deaths but at increased risk for long COVID).

In summary, for older patients, we should be thinking of why we should be using Paxlovid rather than the reason not to treat. We’ll be interested in the survey results to understand the mismatch better, and we look forward to your ideas and feedback to make better use of this treatment for the people who need it the most.

Sincerely yours, Eric J. Topol, MD

Dr. Topol reports no conflicts of interest with Pfizer; he receives no honoraria or speaker fees, does not serve in an advisory role, and has no financial association with the company.

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

Dear Colleagues,

We have a mismatch. The evidence supporting treatment for Paxlovid is compelling for people aged 60 or over, but the older patients in the United States are much less likely to be treated. Not only was there a randomized, placebo-controlled trial of high-risk patients which showed 89% reduction of hospitalizations and deaths (median age, 45), but there have been multiple real-world effectiveness studies subsequently published that have partitioned the benefit for age 65 or older, such as the ones from Israel and Hong Kong (age 60+). Overall, the real-world effectiveness in the first month after treatment is at least as good, if not better, than in the high-risk randomized trial.

But it’s more likely in the United States for a person age 45-50 to get Paxlovid over people age 80 or older. Why? We’re doing the current survey to find out, but the most likely reasons include (1) lack of confidence of benefit; (2) medication interactions; and (3) concerns over rebound.

Let me address each of these briefly. The lack of confidence in benefit stems from the fact that the initial high-risk trial was in unvaccinated individuals. That concern can now be put aside because all of the several real-world studies confirming the protective benefit against hospitalizations and deaths are in people who have been vaccinated, and a significant proportion received booster shots.

The potential medication interactions due to the ritonavir component of the Paxlovid drug combination, attributable to its cytochrome P450 3A4 inhibition, have been unduly emphasized. There are many drug-interaction checkers for Paxlovid, but this one from the University of Liverpool is user friendly, color- and icon-coded, and shows that the vast majority of interactions can be sidestepped by discontinuing the medication of concern for the length of the Paxlovid treatment, 5 days. The simple chart is provided in my recent substack newsletter.

As far as rebound, this problem has unfortunately been exaggerated because of lack of prospective systematic studies and appreciation that a positive test of clinical symptom rebound can occur without Paxlovid. There are soon to be multiple reports that the incidence of Paxlovid rebound is fairly low, in the range of 10%. That concern should not be a reason to withhold treatment.

Now the plot thickens. A new preprint report from the Veterans Health Administration, the largest health care system in the United States, looks at 90-day outcomes of about 9,000 Paxlovid-treated patients and approximately 47,000 controls. Not only was there a 26% reduction in long COVID, but of the breakdown of 12 organs/systems and symptoms, 10 of 12 were significantly reduced with Paxlovid, including pulmonary embolism, deep vein thrombosis, and neurocognitive impairment. There was also a 48% reduction in death and a 30% reduction in hospitalizations after the first 30 days. I have reviewed all of these data and put them in context in a recent newsletter. A key point is that the magnitude of benefit was unaffected by vaccination or booster status, or prior COVID infections, or unvaccinated status. Also, it was the same for men and women, as well as for age > 70 and age < 60. These findings all emphasize a new reason to be using Paxlovid therapy, and if replicated, Paxlovid may even be indicated for younger patients (who are at low risk for hospitalizations and deaths but at increased risk for long COVID).

In summary, for older patients, we should be thinking of why we should be using Paxlovid rather than the reason not to treat. We’ll be interested in the survey results to understand the mismatch better, and we look forward to your ideas and feedback to make better use of this treatment for the people who need it the most.

Sincerely yours, Eric J. Topol, MD

Dr. Topol reports no conflicts of interest with Pfizer; he receives no honoraria or speaker fees, does not serve in an advisory role, and has no financial association with the company.

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