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Mid-career advice
You’ve arrived at an important milestone when someone asks you to give a grand rounds titled ... “Mid-Career Advice.” Yes, I’ve been asked.
I’m flattered to be asked (although I hope I’m not halfway). Mid-career “crisis!” is what Google expected me to talk about when I searched on this topic. Apparently, I’d rather be me today than me in residency – you learn an awful lot in 40K patient visits. Here are a few notes from my journey:
1. Knowing how to care for patients is as important as knowing medicine. The bulk of work to be done in outpatient care depends on bonding, trust, and affecting change efficiently and effectively. Sometimes great diagnostic acumen and procedural skills are needed. Yet, for most, this isn’t hard. Access to differential diagnoses, recommended work-ups, and best practice treatments are easily accessible, just in time. In contrast, it’s often hard to convince patients of their diagnosis and to help them adhere to the best plan.
2. You can do everything right and still have it end up wrong. Medicine is more like poker than chess. In chess, most information is knowable, and there is always one best move. In poker, much is unknown, and a lot depends on chance. You might perform surgery with perfect sterile technique and still, the patient develops an infection. You could prescribe all the best treatments for pyoderma gangrenosum and the disease might still progress. Thinking probabilistically helps me make better choices and sleep better at night, especially when the outcome was not commensurate with the quality of care.
3. Patients are sometimes impertinent, sometimes wrong, sometimes stubborn, sometimes rude. “Restrain your indignation,” Dr. Osler advised his medical students in 1889, and remember that “offences of this kind come; expect them, and do not be vexed.” You might give the best care, the most compassionate, time-generous appointment, and still your patient files a grievance, posts a bad review, fails to follow through, chooses CBD oil instead. Remember, they are just people with all our shortcomings. Do your best to serve and know in your heart that you are enough and have done enough. Then move on; patients are waiting.
4. Adverse outcomes can be devastating, to us as well as to our patients. Any harm caused to a patient or an angry complaint against you can trigger anxiety, regret, and endless ruminating. Sometimes these thoughts become intrusive. Try setting boundaries. Take the time to absorb the discomfort, still knowing you are strong, you are not alone, and failure is sometimes inevitable. Learn what you can, then when you find you’re unable to stop your thoughts, choose an activity (like AngryBirds!) to break your thoughts. You will be a healthier human and provide better care if you can find your equanimity often and early.
5. Amor fati, or “love your fate.” You cannot know what life has planned. Small, seemingly insignificant events in my life changed my path dramatically. I could have been a store manager in Attleboro, Mass., an orthopedic surgeon in Winston-Salem, or a psychologist in Denver. I could never have known then that I’d end up here, as chief of dermatology in San Diego. Rather than depend only on a deliberate strategy with happiness at your destination being “find the job you love,” rely more on an evolving strategy. Do your job and then exploit opportunities as they develop. Forget sunk costs and move ahead. Don’t depend on fate for your happiness or search for a career to fulfill you. Close your eyes and find the happiness in you, then open your eyes and be so right there. Love your fate.
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
You’ve arrived at an important milestone when someone asks you to give a grand rounds titled ... “Mid-Career Advice.” Yes, I’ve been asked.
I’m flattered to be asked (although I hope I’m not halfway). Mid-career “crisis!” is what Google expected me to talk about when I searched on this topic. Apparently, I’d rather be me today than me in residency – you learn an awful lot in 40K patient visits. Here are a few notes from my journey:
1. Knowing how to care for patients is as important as knowing medicine. The bulk of work to be done in outpatient care depends on bonding, trust, and affecting change efficiently and effectively. Sometimes great diagnostic acumen and procedural skills are needed. Yet, for most, this isn’t hard. Access to differential diagnoses, recommended work-ups, and best practice treatments are easily accessible, just in time. In contrast, it’s often hard to convince patients of their diagnosis and to help them adhere to the best plan.
2. You can do everything right and still have it end up wrong. Medicine is more like poker than chess. In chess, most information is knowable, and there is always one best move. In poker, much is unknown, and a lot depends on chance. You might perform surgery with perfect sterile technique and still, the patient develops an infection. You could prescribe all the best treatments for pyoderma gangrenosum and the disease might still progress. Thinking probabilistically helps me make better choices and sleep better at night, especially when the outcome was not commensurate with the quality of care.
3. Patients are sometimes impertinent, sometimes wrong, sometimes stubborn, sometimes rude. “Restrain your indignation,” Dr. Osler advised his medical students in 1889, and remember that “offences of this kind come; expect them, and do not be vexed.” You might give the best care, the most compassionate, time-generous appointment, and still your patient files a grievance, posts a bad review, fails to follow through, chooses CBD oil instead. Remember, they are just people with all our shortcomings. Do your best to serve and know in your heart that you are enough and have done enough. Then move on; patients are waiting.
4. Adverse outcomes can be devastating, to us as well as to our patients. Any harm caused to a patient or an angry complaint against you can trigger anxiety, regret, and endless ruminating. Sometimes these thoughts become intrusive. Try setting boundaries. Take the time to absorb the discomfort, still knowing you are strong, you are not alone, and failure is sometimes inevitable. Learn what you can, then when you find you’re unable to stop your thoughts, choose an activity (like AngryBirds!) to break your thoughts. You will be a healthier human and provide better care if you can find your equanimity often and early.
5. Amor fati, or “love your fate.” You cannot know what life has planned. Small, seemingly insignificant events in my life changed my path dramatically. I could have been a store manager in Attleboro, Mass., an orthopedic surgeon in Winston-Salem, or a psychologist in Denver. I could never have known then that I’d end up here, as chief of dermatology in San Diego. Rather than depend only on a deliberate strategy with happiness at your destination being “find the job you love,” rely more on an evolving strategy. Do your job and then exploit opportunities as they develop. Forget sunk costs and move ahead. Don’t depend on fate for your happiness or search for a career to fulfill you. Close your eyes and find the happiness in you, then open your eyes and be so right there. Love your fate.
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
You’ve arrived at an important milestone when someone asks you to give a grand rounds titled ... “Mid-Career Advice.” Yes, I’ve been asked.
I’m flattered to be asked (although I hope I’m not halfway). Mid-career “crisis!” is what Google expected me to talk about when I searched on this topic. Apparently, I’d rather be me today than me in residency – you learn an awful lot in 40K patient visits. Here are a few notes from my journey:
1. Knowing how to care for patients is as important as knowing medicine. The bulk of work to be done in outpatient care depends on bonding, trust, and affecting change efficiently and effectively. Sometimes great diagnostic acumen and procedural skills are needed. Yet, for most, this isn’t hard. Access to differential diagnoses, recommended work-ups, and best practice treatments are easily accessible, just in time. In contrast, it’s often hard to convince patients of their diagnosis and to help them adhere to the best plan.
2. You can do everything right and still have it end up wrong. Medicine is more like poker than chess. In chess, most information is knowable, and there is always one best move. In poker, much is unknown, and a lot depends on chance. You might perform surgery with perfect sterile technique and still, the patient develops an infection. You could prescribe all the best treatments for pyoderma gangrenosum and the disease might still progress. Thinking probabilistically helps me make better choices and sleep better at night, especially when the outcome was not commensurate with the quality of care.
3. Patients are sometimes impertinent, sometimes wrong, sometimes stubborn, sometimes rude. “Restrain your indignation,” Dr. Osler advised his medical students in 1889, and remember that “offences of this kind come; expect them, and do not be vexed.” You might give the best care, the most compassionate, time-generous appointment, and still your patient files a grievance, posts a bad review, fails to follow through, chooses CBD oil instead. Remember, they are just people with all our shortcomings. Do your best to serve and know in your heart that you are enough and have done enough. Then move on; patients are waiting.
4. Adverse outcomes can be devastating, to us as well as to our patients. Any harm caused to a patient or an angry complaint against you can trigger anxiety, regret, and endless ruminating. Sometimes these thoughts become intrusive. Try setting boundaries. Take the time to absorb the discomfort, still knowing you are strong, you are not alone, and failure is sometimes inevitable. Learn what you can, then when you find you’re unable to stop your thoughts, choose an activity (like AngryBirds!) to break your thoughts. You will be a healthier human and provide better care if you can find your equanimity often and early.
5. Amor fati, or “love your fate.” You cannot know what life has planned. Small, seemingly insignificant events in my life changed my path dramatically. I could have been a store manager in Attleboro, Mass., an orthopedic surgeon in Winston-Salem, or a psychologist in Denver. I could never have known then that I’d end up here, as chief of dermatology in San Diego. Rather than depend only on a deliberate strategy with happiness at your destination being “find the job you love,” rely more on an evolving strategy. Do your job and then exploit opportunities as they develop. Forget sunk costs and move ahead. Don’t depend on fate for your happiness or search for a career to fulfill you. Close your eyes and find the happiness in you, then open your eyes and be so right there. Love your fate.
Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.
Taking vaccines to the next level via mucosal immunity
Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.
Mucosal vs. systemic immunity
Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.1 The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.
Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
Live attenuated influenza vaccine (LAIV) induces mucosal immunity
Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).
Other vaccines likely need to induce mucosal immunity
Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.2 
So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.
Let’s look at a novel “two-site” chlamydia vaccine
Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.3 This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:
1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).
2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).
3. Placebo (saline).
The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).
Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.
Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.
In summary
While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at pdnews@mdedge.com.
References
1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.
2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).
3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.
Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.
Mucosal vs. systemic immunity
Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.1 The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.
Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
Live attenuated influenza vaccine (LAIV) induces mucosal immunity
Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).
Other vaccines likely need to induce mucosal immunity
Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.2
So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.
Let’s look at a novel “two-site” chlamydia vaccine
Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.3 This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:
1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).
2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).
3. Placebo (saline).
The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).
Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.
Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.
In summary
While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at pdnews@mdedge.com.
References
1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.
2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).
3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.
Vaccines are marvelous, and there are many well documented success stories, including rotavirus (RV) vaccines, where a live vaccine is administered to the gastrointestinal mucosa via oral drops. Antigens presented at the mucosal/epithelial surface not only induce systemic serum IgG – as do injectable vaccines – but also induce secretory IgA (sIgA), which is most helpful in diseases that directly affect the mucosa.
Mucosal vs. systemic immunity
Antibody being present on mucosal surfaces (point of initial pathogen contact) has a chance to neutralize the pathogen before it gains a foothold. Pathogen-specific mucosal lymphoid elements (e.g. in Peyer’s patches in the gut) also appear critical for optimal protection.1 The presence of both mucosal immune elements means that infection is severely limited or at times entirely prevented. So virus entering the GI tract causes minimal to no gut lining injury. Hence, there is no or mostly reduced vomiting/diarrhea. A downside of mucosally-administered live vaccines is that preexisting antibody to the vaccine antigens can reduce or block vaccine virus replication in the vaccinee, blunting or preventing protection. Note: Preexisting antibody also affects injectable live vaccines, such as the measles vaccine, similarly.
Classic injectable live or nonlive vaccines provide their most potent protection via systemic cellular responses antibody and/or antibodies in serum and extracellular fluid (ECF) where IgG and IgM are in highest concentrations. So even successful injectable vaccines still allow mucosal infection to start but then intercept further spread and prevent most of the downstream damage (think pertussis) or neutralize an infection-generated toxin (pertussis or tetanus). It usually is only after infection-induced damage occurs that systemic IgG and IgM gain better access to respiratory epithelial surfaces, but still only at a fraction of circulating concentrations. Indeed, pertussis vaccine–induced systemic immunity allows the pathogen to attack and replicate in/on host surface cells, causing toxin release and variable amounts of local mucosal injury/inflammation before vaccine-induced systemic immunity gains adequate access to the pathogen and/or to its toxin which may enter systemic circulation.
Live attenuated influenza vaccine (LAIV) induces mucosal immunity
Another “standard” vaccine that induces mucosal immunity – LAIV – was developed to improve on protection afforded by injectable influenza vaccines (IIVs), but LAIV has had hiccups in the United States. One example is several years of negligible protection against H1N1 disease. As long as LAIV’s vaccine strain had reasonably matched the circulating strains, LAIV worked at least as well as injectable influenza vaccine, and even offered some cross-protection against mildly mismatched strains. But after a number of years of LAIV use, vaccine effectiveness in the United States vs. H1N1 strains appeared to fade due to previously undetected but significant changes in the circulating H1N1 strain. The lesson is that mucosal immunity’s advantages are lost if too much change occurs in the pathogen target for sIgA and mucosally-associated lymphoid tissue cells (MALT)).
Other vaccines likely need to induce mucosal immunity
Protection at the mucosal level will likely be needed for success against norovirus, parainfluenza, respiratory syncytial virus (RSV), Neisseria gonorrhea, and chlamydia. Another helpful aspect of mucosal immunity is that immune cells and sIgA not only reside on the mucosa where the antigen was originally presented, but there is also a reasonable chance that these components will traffic to other mucosal surfaces.2
So intranasal vaccine could be expected to protect distant mucosal surfaces (urogenital, GI, and respiratory), leading to vaccine-induced systemic antibody plus mucosal immunity (sIGA and MALT responses) at each site.
Let’s look at a novel “two-site” chlamydia vaccine
Recently a phase 1 chlamydia vaccine that used a novel two-pronged administration site/schedule was successful at inducing both mucosal and systemic immunity in a proof-of-concept study – achieving the best of both worlds.3 This may be a template for vaccines in years to come. British investigators studied 50 healthy women aged 19-45 years in a double-blind, parallel, randomized, placebo-controlled trial that used a recombinant chlamydia protein subunit antigen (CTH522). The vaccine schedule involved three injectable priming doses followed soon thereafter by two intranasal boosting doses. There were three groups:
1. CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01).
2. CTH522 adjuvanted with aluminum hydroxide (CTH522:AH).
3. Placebo (saline).
The intramuscular (IM) priming schedule was 0, 1, and 4 months. The intranasal vaccine booster doses or placebo were given at 4.5 and 5 months. No related serious adverse reactions occurred. For injectable dosing, the most frequent adverse event was mild local injection-site reactions in all subjects in both vaccine groups vs. in 60% of placebo recipients (P = .053). The adjuvants were the likely cause for local reactions. Intranasal doses had local reactions in 47% of both vaccine groups and 60% of placebo recipients; P = 1.000).
Both vaccines produced systemic IgG seroconversion (including neutralizing antibody) plus small amounts of IgG in the nasal cavity and genital tract in all vaccine recipients; no placebo recipient seroconverted. Interestingly, liposomally-adjuvanted vaccine produced a more rapid systemic IgG response and higher serum titers than the alum-adjuvanted vaccine. Likewise, the IM liposomal vaccine also induced higher but still small mucosal IgG antibody responses (P = .0091). Intranasal IM-induced IgG titers were not boosted by later intranasal vaccine dosing.
Subjects getting liposomal vaccine (but not alum vaccine or placebo) boosters had detectable sIgA titers in both nasal and genital tract secretions. Liposomal vaccine recipients also had fivefold to sixfold higher median titers than alum vaccine recipients after the priming dose, and these higher titers persisted to the end of the study. All liposomal vaccine recipients developed antichlamydial cell-mediated responses vs. 57% alum-adjuvanted vaccine recipients. (P = .01). So both use of two-site dosing and the liposomal adjuvant appeared critical to better responses.
In summary
While this candidate vaccine has hurdles to overcome before coming into routine use, the proof-of-principle that a combination injectable-intranasal vaccine schedule can induce robust systemic and mucosal immunity when given with an appropriate adjuvant is very promising. Adding more vaccines to the schedule then becomes an issue, but that is one of those “good” problems we can deal with later.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospital-Kansas City, Mo. Children’s Mercy Hospital receives grant funding to study two candidate RSV vaccines, receives funding from GlaxoSmithKline for studies on pneumococcal and rotavirus vaccines, and from Pfizer for a study on pneumococcal vaccine on which Dr. Harrison is a sub-investigator. The hospital also receives Centers for Disease Control and Prevention funding under the New Vaccine Surveillance Network for multicenter surveillance of acute respiratory infections, including influenza, RSV, and parainfluenza virus, and also for rotavirus. Email Dr. Harrison at pdnews@mdedge.com.
References
1. PLOS Biology. 2012 Sep 1. doi: 10.1371/journal.pbio.1001397.
2. Mucosal Immunity in the Human Female Reproductive Tract in “Mucosal Immunology,” 4th ed., Volume 2 (Cambridge, MA: Academic Press, 2015, pp. 2097-124).
3. Lancet Infect Dis. 2019. doi: 10.1016/S1473-3099(19)30279-8.
Helping patients find balance between self and other
Cultural considerations require careful assessments on therapists’ part
This column is dedicated to the late Carl C. Bell, MD.
When we work with patients and their families from cultures that are not the culture in which we ourselves were raised, we think more deeply about this balance. In this column, I offer a simple but solid framework for this inquiry.
The first family therapist to crystallize the dialectic between the self and its relationship to others was Murray Bowen, MD. He believed that the differentiation of self from the family was the major task of human development. Dr. Bowen worked in a time when vilification of the “other” was common practice in individual psychotherapies and the goal of individual psychotherapy was the development of a healthy sense of self rather than repairing or developing relationships.
When faced with patients from cultures that are unfamiliar to us, we are less confident about how to assess the balance between self and other. In many cultures, marriages are based on social class and perceived social opportunities and are arranged by the respective families. If you come from a collectivist culture, where the focus is on the belief that the group is more important than the individual, the focus is more on self in relation to a group, belonging to a group, and participating in a group than self-striving. This is most evident in the role of women in many families (as well as in other organizations), in which women shoulder the responsibility for keeping families functional and together.
American culture is focused on serious self-striving. From kindergarten, children are expected to excel and to become the best self that they can be – regardless of the toll this takes on relationships. Self-expression and self-actualization frequently are considered the pinnacle of a life’s achievement. Relationships may take a backseat, often being transitory or utilitarian. This leads to switching relationships, peer groups, and friends – and a strong emphasis on cultivating work relationships.
Exploring Dr. Bowen’s theories
Dr. Bowen posited that the family relational pull affects individual development in a negative way. Despite this, his model is considered one of the most comprehensive explanations for the development of psychological problems from a systemic, relational, and multigenerational perspective.1 He identified the basic self (B-self), which strives for differentiation in contrast to the false/pseudo/relational self (R-self), which strives to meet group or family norms.
Dr. Bowen was the oldest of three and grew up in a small town in Tennessee. His father was the mayor of the town and owned several properties, including the funeral home. Following medical training, Dr. Bowen served during World War II. He accepted a fellowship in surgery at the Mayo Clinic in Rochester, Minn., but his wartime experiences resulted in a change of interest to psychiatry. Dr. Bowen trained at the Menninger Clinic in Topeka, Kan., and in 1954 became the first director of the family division at the National Institute of Mental Health. He and his colleagues studied the families of patients with schizophrenia. They described eight fundamental concepts that supported the important aspects of individual growth. When he moved to Georgetown University in Washington, he developed the Bowen Family Systems Theory.2
Dr. Bowen’s eight concepts
1. Nuclear Family Emotional Process
2. Differentiation of self
3. Triangles
4. Emotional cutoff
5. Family projection process
6. Multigenerational transmission process
7. Sibling position
8. Societal Emotional Process
According to Dr. Bowen, the B-self makes decisions on facts, principles, and intrinsic motivation and decides what they are willing to do/not willing to do based on their own internal ethics. On the other hand, the R-self goes along with everybody else, even when the person internally disagrees. He considered the R-self as wanting acceptance in relationship, possibly changing beliefs to find approval, and striving to be liked. Carmen Knudson-Martin, PhD,3 explored the relationship between the B-self and the R-self and suggested that they exist along two dimensions, both of which are important. My contention is that the R-self is undertheorized and deserves much more exploration.
Developmental psychologists and psychiatrists have focused on understanding the process of psychological maturation of the individual throughout life. However, there is little study of the development of a healthy relationship between self and other. We have, instead, gathered examples and descriptors of the pathological examples of the “other.” We can readily call out enmeshment, the manipulations of the borderline personality disordered, the cold withholding mother – to name the most vilified. What do we know about the healthy R-self?
Measuring the relational self
We have understood the R-self mostly through the study of pathological relationships. For example, pathological parenting has been shown to “result” in individual pathology and as a factor in the development of psychiatric illness. The measurement of the relationship between patient and family member/partner is aimed at elucidating pathology. The supreme example is emotional overinvolvement (EOI).
EOI is an integral part of the construct called expressed emotion and is often measured using the Camberwell Family Interview.4 High EOI has been identified routinely as predictive of worsening of psychiatric illness.5 However, exceptions are found (when you look for them)! In African American families, for example, high EOI is predictive of better outcomes in patients with schizophrenia.6 Jill M. Hooley, DPhil, also has identified that patients with borderline personality disorders do better in families with high EOI.7
A shorter equivalent research tool is the 5-minute speech sample (FMSS). The FMSS analyses 5 minutes of the speech of a parent/family member who is asked to describe the identified patient. EOI is identified by expressions of excessive worry or concern, self-sacrifice, or exaggerated praise. In a study of 223 child-mother dyads, 56.5% of which were Hispanic, use of the FMSS found high EOI predicted externalizing behaviors.8
More recently, psychiatry has sought to identify and measure positive factors, such as family warmth. In Puerto Rican children, high parental warmth was found to be protective against psychiatric disorders.9 In a study of Burmese migrant families from 20 communities in Thailand (513 caregivers and 479 patients with schizophrenia, aged 7-15 years), families were randomized to a waitlist or a 12-week family intervention that promoted warmth.10 The family intervention resulted in increased parental warmth and affection and increased family well-being.
Applying the theories to practice
An adolescent, Jan, does not speak when her mother is in the room. Jan has a small B-self, and her mother has a large B-self. Not only does Jan have to develop a strong B, but she also has to change how she is in relation – she has to change her R-self. For Jan, individual therapy supports the development of a stronger B-self. Working with the patient and her mother, the balance between both B-selves and the joined R-self can be reworked. In essence, the therapist encourages Jan to speak and helps the mother keep her own counsel. This is a situation in which the individual and family intervention are best implemented by the same therapist.
Systemic family therapy, a specific type of family intervention, focuses on how all the R-selves in a family work together as a unit called the family, or F-self. The F-self also has its own family history, as relationship patterns are transmitted and played out through families and play out through subsequent generations. A new type of family therapy called family constellation therapy (FCT) focuses on the F-self as a collection of ancestral selves. This resonates strongly with families who have experienced significant trauma, such as war and Holocaust survivors. FCT is popular in collectivist cultures, where there is a strong belief in the power and influence of ancestors and where the self is understood as an “assemblage of ancestral relationships that often creates problems in the present day.”11 Dr. Bowen recognized this multigenerational pattern as one of his eight fundamental principles.
The patients whom we see often have failing or fractured relationships. They might be stuck in dysfunctional transactional patterns with intimate partners, or they might fail to find a suitable intimate partner. We recognize relational dysfunction such as “codependency,” “symbiosis,” and “enmeshment.” We recognize too much distance, identifying family cutoffs. We still have a long way to go before clinical practice incorporates the importance of assessment and development of healthy relationships in a deep way. A typical question heard across all clinics: Is your partner/family supportive? Not much else is asked in regard to relationships, unless the answer is no. We have yet to develop a good set of inquiring questions that focus on the assessment of healthy relationships.
What can the therapist do to help the patient manage this continual dialectic? The therapist can ask the questions: How important is your B-self versus your R-self? What is the balance between your B-self and your R-self? What do you know about your family or F-self? Is your F-self important to you?
References
1. Nichols MP and Davis S. Family Therapy: Concepts & Methods, 8th ed. (Boston: Allyn & Bacon, 2008).
2. The Bowen Center for the Study of the Family.
3. Knudson-Martin C. Fam J. 1996 Jul 1. doi: 1066480796043002.
4. Leff J and Vaughn C. Expressed Emotion in Families. (New York: The Guilford Press, 1985).
5. Breitborde NJK et al. J Nerv Ment Dis. 2013 Oct;201(10):833-40.
6. Gurak K and de Mamani AW. Fam Process. 2017;56(2):476-86.
7. Hooley JM et al. J Clin Psychiatry. 2010 Aug;71(8):1017-24.
8. Khafi TY et al. J Fam Psychol. 2015 Aug;29(4):585-94.
9. Santesteban-Echarr et al. J Psychiatr Res. 2017 Apr;87:30-6.
10. Puffer ES et al. PLoS One. 2017 Mar 28;12(3):e0172611.
11. Pritzker SE and WL Duncan. Cult Med Psychiatry. 2019 Sep;43(3):468-95.
Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of Working With Families in Family Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals (New York: Routledge, 2013). She has no conflicts of interest.
Cultural considerations require careful assessments on therapists’ part
Cultural considerations require careful assessments on therapists’ part
This column is dedicated to the late Carl C. Bell, MD.
When we work with patients and their families from cultures that are not the culture in which we ourselves were raised, we think more deeply about this balance. In this column, I offer a simple but solid framework for this inquiry.
The first family therapist to crystallize the dialectic between the self and its relationship to others was Murray Bowen, MD. He believed that the differentiation of self from the family was the major task of human development. Dr. Bowen worked in a time when vilification of the “other” was common practice in individual psychotherapies and the goal of individual psychotherapy was the development of a healthy sense of self rather than repairing or developing relationships.
When faced with patients from cultures that are unfamiliar to us, we are less confident about how to assess the balance between self and other. In many cultures, marriages are based on social class and perceived social opportunities and are arranged by the respective families. If you come from a collectivist culture, where the focus is on the belief that the group is more important than the individual, the focus is more on self in relation to a group, belonging to a group, and participating in a group than self-striving. This is most evident in the role of women in many families (as well as in other organizations), in which women shoulder the responsibility for keeping families functional and together.
American culture is focused on serious self-striving. From kindergarten, children are expected to excel and to become the best self that they can be – regardless of the toll this takes on relationships. Self-expression and self-actualization frequently are considered the pinnacle of a life’s achievement. Relationships may take a backseat, often being transitory or utilitarian. This leads to switching relationships, peer groups, and friends – and a strong emphasis on cultivating work relationships.
Exploring Dr. Bowen’s theories
Dr. Bowen posited that the family relational pull affects individual development in a negative way. Despite this, his model is considered one of the most comprehensive explanations for the development of psychological problems from a systemic, relational, and multigenerational perspective.1 He identified the basic self (B-self), which strives for differentiation in contrast to the false/pseudo/relational self (R-self), which strives to meet group or family norms.
Dr. Bowen was the oldest of three and grew up in a small town in Tennessee. His father was the mayor of the town and owned several properties, including the funeral home. Following medical training, Dr. Bowen served during World War II. He accepted a fellowship in surgery at the Mayo Clinic in Rochester, Minn., but his wartime experiences resulted in a change of interest to psychiatry. Dr. Bowen trained at the Menninger Clinic in Topeka, Kan., and in 1954 became the first director of the family division at the National Institute of Mental Health. He and his colleagues studied the families of patients with schizophrenia. They described eight fundamental concepts that supported the important aspects of individual growth. When he moved to Georgetown University in Washington, he developed the Bowen Family Systems Theory.2
Dr. Bowen’s eight concepts
1. Nuclear Family Emotional Process
2. Differentiation of self
3. Triangles
4. Emotional cutoff
5. Family projection process
6. Multigenerational transmission process
7. Sibling position
8. Societal Emotional Process
According to Dr. Bowen, the B-self makes decisions on facts, principles, and intrinsic motivation and decides what they are willing to do/not willing to do based on their own internal ethics. On the other hand, the R-self goes along with everybody else, even when the person internally disagrees. He considered the R-self as wanting acceptance in relationship, possibly changing beliefs to find approval, and striving to be liked. Carmen Knudson-Martin, PhD,3 explored the relationship between the B-self and the R-self and suggested that they exist along two dimensions, both of which are important. My contention is that the R-self is undertheorized and deserves much more exploration.
Developmental psychologists and psychiatrists have focused on understanding the process of psychological maturation of the individual throughout life. However, there is little study of the development of a healthy relationship between self and other. We have, instead, gathered examples and descriptors of the pathological examples of the “other.” We can readily call out enmeshment, the manipulations of the borderline personality disordered, the cold withholding mother – to name the most vilified. What do we know about the healthy R-self?
Measuring the relational self
We have understood the R-self mostly through the study of pathological relationships. For example, pathological parenting has been shown to “result” in individual pathology and as a factor in the development of psychiatric illness. The measurement of the relationship between patient and family member/partner is aimed at elucidating pathology. The supreme example is emotional overinvolvement (EOI).
EOI is an integral part of the construct called expressed emotion and is often measured using the Camberwell Family Interview.4 High EOI has been identified routinely as predictive of worsening of psychiatric illness.5 However, exceptions are found (when you look for them)! In African American families, for example, high EOI is predictive of better outcomes in patients with schizophrenia.6 Jill M. Hooley, DPhil, also has identified that patients with borderline personality disorders do better in families with high EOI.7
A shorter equivalent research tool is the 5-minute speech sample (FMSS). The FMSS analyses 5 minutes of the speech of a parent/family member who is asked to describe the identified patient. EOI is identified by expressions of excessive worry or concern, self-sacrifice, or exaggerated praise. In a study of 223 child-mother dyads, 56.5% of which were Hispanic, use of the FMSS found high EOI predicted externalizing behaviors.8
More recently, psychiatry has sought to identify and measure positive factors, such as family warmth. In Puerto Rican children, high parental warmth was found to be protective against psychiatric disorders.9 In a study of Burmese migrant families from 20 communities in Thailand (513 caregivers and 479 patients with schizophrenia, aged 7-15 years), families were randomized to a waitlist or a 12-week family intervention that promoted warmth.10 The family intervention resulted in increased parental warmth and affection and increased family well-being.
Applying the theories to practice
An adolescent, Jan, does not speak when her mother is in the room. Jan has a small B-self, and her mother has a large B-self. Not only does Jan have to develop a strong B, but she also has to change how she is in relation – she has to change her R-self. For Jan, individual therapy supports the development of a stronger B-self. Working with the patient and her mother, the balance between both B-selves and the joined R-self can be reworked. In essence, the therapist encourages Jan to speak and helps the mother keep her own counsel. This is a situation in which the individual and family intervention are best implemented by the same therapist.
Systemic family therapy, a specific type of family intervention, focuses on how all the R-selves in a family work together as a unit called the family, or F-self. The F-self also has its own family history, as relationship patterns are transmitted and played out through families and play out through subsequent generations. A new type of family therapy called family constellation therapy (FCT) focuses on the F-self as a collection of ancestral selves. This resonates strongly with families who have experienced significant trauma, such as war and Holocaust survivors. FCT is popular in collectivist cultures, where there is a strong belief in the power and influence of ancestors and where the self is understood as an “assemblage of ancestral relationships that often creates problems in the present day.”11 Dr. Bowen recognized this multigenerational pattern as one of his eight fundamental principles.
The patients whom we see often have failing or fractured relationships. They might be stuck in dysfunctional transactional patterns with intimate partners, or they might fail to find a suitable intimate partner. We recognize relational dysfunction such as “codependency,” “symbiosis,” and “enmeshment.” We recognize too much distance, identifying family cutoffs. We still have a long way to go before clinical practice incorporates the importance of assessment and development of healthy relationships in a deep way. A typical question heard across all clinics: Is your partner/family supportive? Not much else is asked in regard to relationships, unless the answer is no. We have yet to develop a good set of inquiring questions that focus on the assessment of healthy relationships.
What can the therapist do to help the patient manage this continual dialectic? The therapist can ask the questions: How important is your B-self versus your R-self? What is the balance between your B-self and your R-self? What do you know about your family or F-self? Is your F-self important to you?
References
1. Nichols MP and Davis S. Family Therapy: Concepts & Methods, 8th ed. (Boston: Allyn & Bacon, 2008).
2. The Bowen Center for the Study of the Family.
3. Knudson-Martin C. Fam J. 1996 Jul 1. doi: 1066480796043002.
4. Leff J and Vaughn C. Expressed Emotion in Families. (New York: The Guilford Press, 1985).
5. Breitborde NJK et al. J Nerv Ment Dis. 2013 Oct;201(10):833-40.
6. Gurak K and de Mamani AW. Fam Process. 2017;56(2):476-86.
7. Hooley JM et al. J Clin Psychiatry. 2010 Aug;71(8):1017-24.
8. Khafi TY et al. J Fam Psychol. 2015 Aug;29(4):585-94.
9. Santesteban-Echarr et al. J Psychiatr Res. 2017 Apr;87:30-6.
10. Puffer ES et al. PLoS One. 2017 Mar 28;12(3):e0172611.
11. Pritzker SE and WL Duncan. Cult Med Psychiatry. 2019 Sep;43(3):468-95.
Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of Working With Families in Family Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals (New York: Routledge, 2013). She has no conflicts of interest.
This column is dedicated to the late Carl C. Bell, MD.
When we work with patients and their families from cultures that are not the culture in which we ourselves were raised, we think more deeply about this balance. In this column, I offer a simple but solid framework for this inquiry.
The first family therapist to crystallize the dialectic between the self and its relationship to others was Murray Bowen, MD. He believed that the differentiation of self from the family was the major task of human development. Dr. Bowen worked in a time when vilification of the “other” was common practice in individual psychotherapies and the goal of individual psychotherapy was the development of a healthy sense of self rather than repairing or developing relationships.
When faced with patients from cultures that are unfamiliar to us, we are less confident about how to assess the balance between self and other. In many cultures, marriages are based on social class and perceived social opportunities and are arranged by the respective families. If you come from a collectivist culture, where the focus is on the belief that the group is more important than the individual, the focus is more on self in relation to a group, belonging to a group, and participating in a group than self-striving. This is most evident in the role of women in many families (as well as in other organizations), in which women shoulder the responsibility for keeping families functional and together.
American culture is focused on serious self-striving. From kindergarten, children are expected to excel and to become the best self that they can be – regardless of the toll this takes on relationships. Self-expression and self-actualization frequently are considered the pinnacle of a life’s achievement. Relationships may take a backseat, often being transitory or utilitarian. This leads to switching relationships, peer groups, and friends – and a strong emphasis on cultivating work relationships.
Exploring Dr. Bowen’s theories
Dr. Bowen posited that the family relational pull affects individual development in a negative way. Despite this, his model is considered one of the most comprehensive explanations for the development of psychological problems from a systemic, relational, and multigenerational perspective.1 He identified the basic self (B-self), which strives for differentiation in contrast to the false/pseudo/relational self (R-self), which strives to meet group or family norms.
Dr. Bowen was the oldest of three and grew up in a small town in Tennessee. His father was the mayor of the town and owned several properties, including the funeral home. Following medical training, Dr. Bowen served during World War II. He accepted a fellowship in surgery at the Mayo Clinic in Rochester, Minn., but his wartime experiences resulted in a change of interest to psychiatry. Dr. Bowen trained at the Menninger Clinic in Topeka, Kan., and in 1954 became the first director of the family division at the National Institute of Mental Health. He and his colleagues studied the families of patients with schizophrenia. They described eight fundamental concepts that supported the important aspects of individual growth. When he moved to Georgetown University in Washington, he developed the Bowen Family Systems Theory.2
Dr. Bowen’s eight concepts
1. Nuclear Family Emotional Process
2. Differentiation of self
3. Triangles
4. Emotional cutoff
5. Family projection process
6. Multigenerational transmission process
7. Sibling position
8. Societal Emotional Process
According to Dr. Bowen, the B-self makes decisions on facts, principles, and intrinsic motivation and decides what they are willing to do/not willing to do based on their own internal ethics. On the other hand, the R-self goes along with everybody else, even when the person internally disagrees. He considered the R-self as wanting acceptance in relationship, possibly changing beliefs to find approval, and striving to be liked. Carmen Knudson-Martin, PhD,3 explored the relationship between the B-self and the R-self and suggested that they exist along two dimensions, both of which are important. My contention is that the R-self is undertheorized and deserves much more exploration.
Developmental psychologists and psychiatrists have focused on understanding the process of psychological maturation of the individual throughout life. However, there is little study of the development of a healthy relationship between self and other. We have, instead, gathered examples and descriptors of the pathological examples of the “other.” We can readily call out enmeshment, the manipulations of the borderline personality disordered, the cold withholding mother – to name the most vilified. What do we know about the healthy R-self?
Measuring the relational self
We have understood the R-self mostly through the study of pathological relationships. For example, pathological parenting has been shown to “result” in individual pathology and as a factor in the development of psychiatric illness. The measurement of the relationship between patient and family member/partner is aimed at elucidating pathology. The supreme example is emotional overinvolvement (EOI).
EOI is an integral part of the construct called expressed emotion and is often measured using the Camberwell Family Interview.4 High EOI has been identified routinely as predictive of worsening of psychiatric illness.5 However, exceptions are found (when you look for them)! In African American families, for example, high EOI is predictive of better outcomes in patients with schizophrenia.6 Jill M. Hooley, DPhil, also has identified that patients with borderline personality disorders do better in families with high EOI.7
A shorter equivalent research tool is the 5-minute speech sample (FMSS). The FMSS analyses 5 minutes of the speech of a parent/family member who is asked to describe the identified patient. EOI is identified by expressions of excessive worry or concern, self-sacrifice, or exaggerated praise. In a study of 223 child-mother dyads, 56.5% of which were Hispanic, use of the FMSS found high EOI predicted externalizing behaviors.8
More recently, psychiatry has sought to identify and measure positive factors, such as family warmth. In Puerto Rican children, high parental warmth was found to be protective against psychiatric disorders.9 In a study of Burmese migrant families from 20 communities in Thailand (513 caregivers and 479 patients with schizophrenia, aged 7-15 years), families were randomized to a waitlist or a 12-week family intervention that promoted warmth.10 The family intervention resulted in increased parental warmth and affection and increased family well-being.
Applying the theories to practice
An adolescent, Jan, does not speak when her mother is in the room. Jan has a small B-self, and her mother has a large B-self. Not only does Jan have to develop a strong B, but she also has to change how she is in relation – she has to change her R-self. For Jan, individual therapy supports the development of a stronger B-self. Working with the patient and her mother, the balance between both B-selves and the joined R-self can be reworked. In essence, the therapist encourages Jan to speak and helps the mother keep her own counsel. This is a situation in which the individual and family intervention are best implemented by the same therapist.
Systemic family therapy, a specific type of family intervention, focuses on how all the R-selves in a family work together as a unit called the family, or F-self. The F-self also has its own family history, as relationship patterns are transmitted and played out through families and play out through subsequent generations. A new type of family therapy called family constellation therapy (FCT) focuses on the F-self as a collection of ancestral selves. This resonates strongly with families who have experienced significant trauma, such as war and Holocaust survivors. FCT is popular in collectivist cultures, where there is a strong belief in the power and influence of ancestors and where the self is understood as an “assemblage of ancestral relationships that often creates problems in the present day.”11 Dr. Bowen recognized this multigenerational pattern as one of his eight fundamental principles.
The patients whom we see often have failing or fractured relationships. They might be stuck in dysfunctional transactional patterns with intimate partners, or they might fail to find a suitable intimate partner. We recognize relational dysfunction such as “codependency,” “symbiosis,” and “enmeshment.” We recognize too much distance, identifying family cutoffs. We still have a long way to go before clinical practice incorporates the importance of assessment and development of healthy relationships in a deep way. A typical question heard across all clinics: Is your partner/family supportive? Not much else is asked in regard to relationships, unless the answer is no. We have yet to develop a good set of inquiring questions that focus on the assessment of healthy relationships.
What can the therapist do to help the patient manage this continual dialectic? The therapist can ask the questions: How important is your B-self versus your R-self? What is the balance between your B-self and your R-self? What do you know about your family or F-self? Is your F-self important to you?
References
1. Nichols MP and Davis S. Family Therapy: Concepts & Methods, 8th ed. (Boston: Allyn & Bacon, 2008).
2. The Bowen Center for the Study of the Family.
3. Knudson-Martin C. Fam J. 1996 Jul 1. doi: 1066480796043002.
4. Leff J and Vaughn C. Expressed Emotion in Families. (New York: The Guilford Press, 1985).
5. Breitborde NJK et al. J Nerv Ment Dis. 2013 Oct;201(10):833-40.
6. Gurak K and de Mamani AW. Fam Process. 2017;56(2):476-86.
7. Hooley JM et al. J Clin Psychiatry. 2010 Aug;71(8):1017-24.
8. Khafi TY et al. J Fam Psychol. 2015 Aug;29(4):585-94.
9. Santesteban-Echarr et al. J Psychiatr Res. 2017 Apr;87:30-6.
10. Puffer ES et al. PLoS One. 2017 Mar 28;12(3):e0172611.
11. Pritzker SE and WL Duncan. Cult Med Psychiatry. 2019 Sep;43(3):468-95.
Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of Working With Families in Family Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals (New York: Routledge, 2013). She has no conflicts of interest.
Observation versus inpatient status
A dilemma for hospitalists and patients
A federal effort to reduce health care expenditures has left many older Medicare recipients experiencing the sticker shock of “observation status.” Patients who are not sick enough to meet inpatient admission criteria, however, still require hospitalization, and may be placed under Medicare observation care.
Seniors can get frustrated, confused, and anxious as their status can be changed while they are in the hospital, and they may receive large medical bills after they are discharged. The Centers for Medicare & Medicaid Services’ “3-day rule” mandates that Medicare will not pay for skilled nursing facility care unless the patient is admitted as an “inpatient” for at least 3 days. Observation days do not count towards this 3-day hospital stay.
There has been an increase in outpatient services over the years since 2006. The 2018 State of Hospital Medicine Report (SoHM) highlights the percentage of discharges based on hospitalists’ billed Current Procedural Terminology codes. Codes 99217 (observation discharge) and 99238-99239 (inpatient discharge) were used to calculate the percentages. 80.7% of adult medicine hospitalist discharges were coded using inpatient discharge codes, while 19.3% of patients were discharged with observation discharge codes.
In the 2016 SoHM report, the ratio was 76.0% inpatient and 21.1% observation codes and in the 2014 report we saw 80.3% inpatient and 16.1% observation discharges (see table 1). But in both of those surveys, same-day admission/discharge codes were also separately reported, which did not occur in 2018. That makes year-over-year comparison of the data challenging.
Interestingly, the 2017 CMS data on Evaluation and Management Codes by Specialty for the first time included separate data for hospitalists, based on hospitalists who credentialed with Medicare using the new C6 specialty code. Based on that data, when looking only at inpatient (99238-99239) and observation (99217) codes, 83% of the discharges were inpatient and 17% were observation.
Physicians feel the pressure of strained patient-physician relationships as a consequence of patients feeling the brunt of the financing gap related to observation status. Patients often feel they were not warned adequately about the financial ramifications of observation status. Even if Medicare beneficiaries have received the Medicare Outpatient Observation Notice, outlined by the Notice of Observation Treatment and Implication for Care Eligibility Act, they have no rights to appeal.
Currently Medicare beneficiaries admitted as inpatients only incur a Part A deductible; they are not liable for tests, procedures, and nursing care. On the other hand, in observation status all services are billed separately. For Medicare Part B services (which covers observation care) patients must pay 20% of services after the Part B deductible, which could result in a huge financial burden. Costs for skilled nursing facilities, when they are not covered by Medicare Part A, because of the 3-day rule, can easily go up to $20,000 or more. Medicare beneficiaries have no cap on costs for an observation stay. In some cases, hospitals have to apply a condition code 44 and retroactively change the stay to observation status.
I attended the 2019 Society of Hospital Medicine Annual Conference in Washington. Hospitalists from all parts of the country advocated on Capitol Hill against the “observation bill,” and “meet and greets” with congressional representatives increased their opposition to the bill. These efforts may work in favor of protecting patients from surprise medical bills. Hospital medicine physicians are on the front lines for providing health care in the hospital setting; they have demanded a fix to this legislative loophole which brings high out of pocket costs to our nation’s most vulnerable seniors. The observation status “2-midnight rule” utilized by CMS has increased financial barriers and decreased access to postacute care, affecting the provision of high-quality care for patients.
My hospital has a utilization review committee which reviews all cases to determine the appropriateness of an inpatient versus an observation designation. (An interesting question is whether the financial resources used to support this additional staff could be better assigned to provide high-quality care.) Distribution of these patients is determined on very specific criteria as outlined by Medicare. Observation is basically considered a billing method implemented by payers to decrease dollars paid to acute care hospitals for inpatient care. It pertains to admission status, not to the level of care provided in the hospital. Unfortunately, it is felt that no two payers define observation the same way. A few examples of common observation diagnoses are chest pain, abdominal pain, syncope, and migraine headache; in other words, patients with diagnoses where it is suspected that a less than 24-hour stay in the hospital could be sufficient.
Observation care is increasing and can sometimes contribute to work flow impediments and frustrations in hospitalists; thus, hospitalists are demanding reform. It has been proposed that observation could be eliminated altogether by creating a payment blend of inpatient/outpatient rates. Another option could be to assign lower Diagnosis Related Group coding to lower acuity disease processes, instead of separate observation reimbursement.
Patients and doctors lament that “Once you are in the hospital, you are admitted!” I don’t know the right answer that would solve the observation versus inpatient dilemma, but it is intriguing to consider changes in policy that might focus on the complete elimination of observation status.
Dr. Puri is a hospitalist at Lahey Hospital and Medical Center in Burlington, Mass.
A dilemma for hospitalists and patients
A dilemma for hospitalists and patients
A federal effort to reduce health care expenditures has left many older Medicare recipients experiencing the sticker shock of “observation status.” Patients who are not sick enough to meet inpatient admission criteria, however, still require hospitalization, and may be placed under Medicare observation care.
Seniors can get frustrated, confused, and anxious as their status can be changed while they are in the hospital, and they may receive large medical bills after they are discharged. The Centers for Medicare & Medicaid Services’ “3-day rule” mandates that Medicare will not pay for skilled nursing facility care unless the patient is admitted as an “inpatient” for at least 3 days. Observation days do not count towards this 3-day hospital stay.
There has been an increase in outpatient services over the years since 2006. The 2018 State of Hospital Medicine Report (SoHM) highlights the percentage of discharges based on hospitalists’ billed Current Procedural Terminology codes. Codes 99217 (observation discharge) and 99238-99239 (inpatient discharge) were used to calculate the percentages. 80.7% of adult medicine hospitalist discharges were coded using inpatient discharge codes, while 19.3% of patients were discharged with observation discharge codes.
In the 2016 SoHM report, the ratio was 76.0% inpatient and 21.1% observation codes and in the 2014 report we saw 80.3% inpatient and 16.1% observation discharges (see table 1). But in both of those surveys, same-day admission/discharge codes were also separately reported, which did not occur in 2018. That makes year-over-year comparison of the data challenging.
Interestingly, the 2017 CMS data on Evaluation and Management Codes by Specialty for the first time included separate data for hospitalists, based on hospitalists who credentialed with Medicare using the new C6 specialty code. Based on that data, when looking only at inpatient (99238-99239) and observation (99217) codes, 83% of the discharges were inpatient and 17% were observation.
Physicians feel the pressure of strained patient-physician relationships as a consequence of patients feeling the brunt of the financing gap related to observation status. Patients often feel they were not warned adequately about the financial ramifications of observation status. Even if Medicare beneficiaries have received the Medicare Outpatient Observation Notice, outlined by the Notice of Observation Treatment and Implication for Care Eligibility Act, they have no rights to appeal.
Currently Medicare beneficiaries admitted as inpatients only incur a Part A deductible; they are not liable for tests, procedures, and nursing care. On the other hand, in observation status all services are billed separately. For Medicare Part B services (which covers observation care) patients must pay 20% of services after the Part B deductible, which could result in a huge financial burden. Costs for skilled nursing facilities, when they are not covered by Medicare Part A, because of the 3-day rule, can easily go up to $20,000 or more. Medicare beneficiaries have no cap on costs for an observation stay. In some cases, hospitals have to apply a condition code 44 and retroactively change the stay to observation status.
I attended the 2019 Society of Hospital Medicine Annual Conference in Washington. Hospitalists from all parts of the country advocated on Capitol Hill against the “observation bill,” and “meet and greets” with congressional representatives increased their opposition to the bill. These efforts may work in favor of protecting patients from surprise medical bills. Hospital medicine physicians are on the front lines for providing health care in the hospital setting; they have demanded a fix to this legislative loophole which brings high out of pocket costs to our nation’s most vulnerable seniors. The observation status “2-midnight rule” utilized by CMS has increased financial barriers and decreased access to postacute care, affecting the provision of high-quality care for patients.
My hospital has a utilization review committee which reviews all cases to determine the appropriateness of an inpatient versus an observation designation. (An interesting question is whether the financial resources used to support this additional staff could be better assigned to provide high-quality care.) Distribution of these patients is determined on very specific criteria as outlined by Medicare. Observation is basically considered a billing method implemented by payers to decrease dollars paid to acute care hospitals for inpatient care. It pertains to admission status, not to the level of care provided in the hospital. Unfortunately, it is felt that no two payers define observation the same way. A few examples of common observation diagnoses are chest pain, abdominal pain, syncope, and migraine headache; in other words, patients with diagnoses where it is suspected that a less than 24-hour stay in the hospital could be sufficient.
Observation care is increasing and can sometimes contribute to work flow impediments and frustrations in hospitalists; thus, hospitalists are demanding reform. It has been proposed that observation could be eliminated altogether by creating a payment blend of inpatient/outpatient rates. Another option could be to assign lower Diagnosis Related Group coding to lower acuity disease processes, instead of separate observation reimbursement.
Patients and doctors lament that “Once you are in the hospital, you are admitted!” I don’t know the right answer that would solve the observation versus inpatient dilemma, but it is intriguing to consider changes in policy that might focus on the complete elimination of observation status.
Dr. Puri is a hospitalist at Lahey Hospital and Medical Center in Burlington, Mass.
A federal effort to reduce health care expenditures has left many older Medicare recipients experiencing the sticker shock of “observation status.” Patients who are not sick enough to meet inpatient admission criteria, however, still require hospitalization, and may be placed under Medicare observation care.
Seniors can get frustrated, confused, and anxious as their status can be changed while they are in the hospital, and they may receive large medical bills after they are discharged. The Centers for Medicare & Medicaid Services’ “3-day rule” mandates that Medicare will not pay for skilled nursing facility care unless the patient is admitted as an “inpatient” for at least 3 days. Observation days do not count towards this 3-day hospital stay.
There has been an increase in outpatient services over the years since 2006. The 2018 State of Hospital Medicine Report (SoHM) highlights the percentage of discharges based on hospitalists’ billed Current Procedural Terminology codes. Codes 99217 (observation discharge) and 99238-99239 (inpatient discharge) were used to calculate the percentages. 80.7% of adult medicine hospitalist discharges were coded using inpatient discharge codes, while 19.3% of patients were discharged with observation discharge codes.
In the 2016 SoHM report, the ratio was 76.0% inpatient and 21.1% observation codes and in the 2014 report we saw 80.3% inpatient and 16.1% observation discharges (see table 1). But in both of those surveys, same-day admission/discharge codes were also separately reported, which did not occur in 2018. That makes year-over-year comparison of the data challenging.
Interestingly, the 2017 CMS data on Evaluation and Management Codes by Specialty for the first time included separate data for hospitalists, based on hospitalists who credentialed with Medicare using the new C6 specialty code. Based on that data, when looking only at inpatient (99238-99239) and observation (99217) codes, 83% of the discharges were inpatient and 17% were observation.
Physicians feel the pressure of strained patient-physician relationships as a consequence of patients feeling the brunt of the financing gap related to observation status. Patients often feel they were not warned adequately about the financial ramifications of observation status. Even if Medicare beneficiaries have received the Medicare Outpatient Observation Notice, outlined by the Notice of Observation Treatment and Implication for Care Eligibility Act, they have no rights to appeal.
Currently Medicare beneficiaries admitted as inpatients only incur a Part A deductible; they are not liable for tests, procedures, and nursing care. On the other hand, in observation status all services are billed separately. For Medicare Part B services (which covers observation care) patients must pay 20% of services after the Part B deductible, which could result in a huge financial burden. Costs for skilled nursing facilities, when they are not covered by Medicare Part A, because of the 3-day rule, can easily go up to $20,000 or more. Medicare beneficiaries have no cap on costs for an observation stay. In some cases, hospitals have to apply a condition code 44 and retroactively change the stay to observation status.
I attended the 2019 Society of Hospital Medicine Annual Conference in Washington. Hospitalists from all parts of the country advocated on Capitol Hill against the “observation bill,” and “meet and greets” with congressional representatives increased their opposition to the bill. These efforts may work in favor of protecting patients from surprise medical bills. Hospital medicine physicians are on the front lines for providing health care in the hospital setting; they have demanded a fix to this legislative loophole which brings high out of pocket costs to our nation’s most vulnerable seniors. The observation status “2-midnight rule” utilized by CMS has increased financial barriers and decreased access to postacute care, affecting the provision of high-quality care for patients.
My hospital has a utilization review committee which reviews all cases to determine the appropriateness of an inpatient versus an observation designation. (An interesting question is whether the financial resources used to support this additional staff could be better assigned to provide high-quality care.) Distribution of these patients is determined on very specific criteria as outlined by Medicare. Observation is basically considered a billing method implemented by payers to decrease dollars paid to acute care hospitals for inpatient care. It pertains to admission status, not to the level of care provided in the hospital. Unfortunately, it is felt that no two payers define observation the same way. A few examples of common observation diagnoses are chest pain, abdominal pain, syncope, and migraine headache; in other words, patients with diagnoses where it is suspected that a less than 24-hour stay in the hospital could be sufficient.
Observation care is increasing and can sometimes contribute to work flow impediments and frustrations in hospitalists; thus, hospitalists are demanding reform. It has been proposed that observation could be eliminated altogether by creating a payment blend of inpatient/outpatient rates. Another option could be to assign lower Diagnosis Related Group coding to lower acuity disease processes, instead of separate observation reimbursement.
Patients and doctors lament that “Once you are in the hospital, you are admitted!” I don’t know the right answer that would solve the observation versus inpatient dilemma, but it is intriguing to consider changes in policy that might focus on the complete elimination of observation status.
Dr. Puri is a hospitalist at Lahey Hospital and Medical Center in Burlington, Mass.
My patient tells me that they are transgender – now what?
I am privileged to work in a university hospital system where I have access to colleagues with expertise in LGBT health; however, medical providers in the community may not enjoy such resources. Many transgender and gender-diverse (TGD) youth now are seeking help from their community primary care providers to affirm their gender identity, but many community primary care providers do not have the luxury of referring these patients to an expert in gender-affirming care when their TGD patients express the desire to affirm their gender through medical and surgical means. This is even more difficult if the nearest referral center is hundreds of miles away. Nevertheless,
If a TGD youth discloses their gender identity to you, it is critical that you make the patient feel safe and supported. Showing support is important in maintaining rapport between you and the patient. Furthermore, you may be one of the very few adults in the child’s life whom they can trust.
First of all, thank them. For many TGD patients, disclosing their gender identity to a health care provider can be a herculean task. They may have spent many hours trying to find the right words to say to disclose an important aspect of themselves to you. They also probably spent a fair amount of time worrying about whether or not you would react positively to this disclosure. This fear is reasonable. About one-fifth of transgender people have reported being kicked out of a medical practice because of their disclosure of their gender identity.1
Secondly, assure the TGD patient that your treatment would be no different from the care provided for other patients. Discrimination from a health care provider has frequently been reported by TGD patients1 and is expected from this population.2 By emphasizing this, you have signaled to them that you are committed to treating them with dignity and respect. Furthermore, signal your commitment to this treatment by making the clinic a safe and welcoming place for LGBT youth. Several resources exist that can help with this. The American Medical Association provides a good example on how to draft a nondiscrimination statement that can be posted in waiting areas;3 the Fenway Institute has a good example of an intake form that is LGBT friendly.4
In addition, a good way to help affirm their gender identity is to tell them that being transgender or gender-diverse is normal and healthy. Many times, TGD youth will hear narratives that gender diversity is pathological or aberrant; however, hearing that they are healthy and normal, especially from a health care provider, can make a powerful impact on feeling supported and affirmed.
Furthermore, inform your TGD youth of their right to confidentiality. Many TGD youth may not be out to their parents, and you may be the first person to whom they disclosed their gender identity. This is especially helpful if you describe their right to and the limits of confidentiality (e.g., suicidality) at the beginning of the visit. Assurance of confidentiality is a vital reason adolescents and young adults seek health care from a medical provider,5 and the same can be said of TGD youth; however, keep in mind that if they do desire to transition using cross-sex hormones or surgery, parental permission is required.
If they are not out to their parents and they are planning to come out to their parents, offer to be there when they do. Having someone to support the child – someone who is a medical provider – can add to the sense of legitimacy that what the child is experiencing is normal and healthy. Providing guidance on how parents can support their TGD child is essential for successful affirmation, and some suggestions can be found in an LGBT Youth Consult column I wrote titled, “Guidance for parents of LGBT youth.”
If you practice in a location where the nearest expert in gender-affirming care can be hundreds of miles away, educate yourself on gender-affirming care. Several guidelines are available. The World Professional Society for Transgender Standards of Care (SOC) focuses on the mental health aspects of gender-affirming care. The SOC recommends, but no longer requires, letters from a mental health therapist to start gender-affirming medical treatments and does allow for a discussion between you and the patient on the risks, benefits, alternatives, unknowns, limitations of treatment, and risks of not treating (i.e., obtaining informed consent) as the threshold for hormone therapy.6 This approach, known as the “informed consent model,” can be helpful in expanding health care access for TGD youth. Furthermore, there’s the Endocrine Society Clinical Practice Guidelines7 and the University of California, San Francisco, Guidelines,8 which focus on the medical aspects of gender-affirming care, such as when to start pubertal blockers and dosing for cross-sex hormones. Finally, there are resources that allow providers to consult an expert remotely for more complicated cases. Transline is a transgender medical consultation service staffed by medical providers with expertise in gender-affirming care. Providers can learn more about this valuable service on the website: http://project-health.org/transline/.
Working in a major medical center is not necessary in providing gender-affirming care to TGD youth. Being respectful, supportive, and having the willingness to learn are the minimal requirements. Resources are available to help guide you on the more technical aspects of gender-affirming care. Maintaining a supportive environment and using these resources will help you expand health care access for this population.
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@mdedge.com.
References
1. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
2. Psychol Bull. 2003 Sep;129(5):674-97.
3. “Creating an LGBTQ-friendly practice,” American Medical Association.
4. Fenway Health Client Registration Form.
5. JAMA. 1993 Mar 17;269(11):1404-7.
6. Int J Transgenderism 2012;13:165-232.
7. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-903.
8. “Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People,” 2nd edition (San Francisco, CA: University of California, San Francisco, June 17, 2016).
I am privileged to work in a university hospital system where I have access to colleagues with expertise in LGBT health; however, medical providers in the community may not enjoy such resources. Many transgender and gender-diverse (TGD) youth now are seeking help from their community primary care providers to affirm their gender identity, but many community primary care providers do not have the luxury of referring these patients to an expert in gender-affirming care when their TGD patients express the desire to affirm their gender through medical and surgical means. This is even more difficult if the nearest referral center is hundreds of miles away. Nevertheless,
If a TGD youth discloses their gender identity to you, it is critical that you make the patient feel safe and supported. Showing support is important in maintaining rapport between you and the patient. Furthermore, you may be one of the very few adults in the child’s life whom they can trust.
First of all, thank them. For many TGD patients, disclosing their gender identity to a health care provider can be a herculean task. They may have spent many hours trying to find the right words to say to disclose an important aspect of themselves to you. They also probably spent a fair amount of time worrying about whether or not you would react positively to this disclosure. This fear is reasonable. About one-fifth of transgender people have reported being kicked out of a medical practice because of their disclosure of their gender identity.1
Secondly, assure the TGD patient that your treatment would be no different from the care provided for other patients. Discrimination from a health care provider has frequently been reported by TGD patients1 and is expected from this population.2 By emphasizing this, you have signaled to them that you are committed to treating them with dignity and respect. Furthermore, signal your commitment to this treatment by making the clinic a safe and welcoming place for LGBT youth. Several resources exist that can help with this. The American Medical Association provides a good example on how to draft a nondiscrimination statement that can be posted in waiting areas;3 the Fenway Institute has a good example of an intake form that is LGBT friendly.4
In addition, a good way to help affirm their gender identity is to tell them that being transgender or gender-diverse is normal and healthy. Many times, TGD youth will hear narratives that gender diversity is pathological or aberrant; however, hearing that they are healthy and normal, especially from a health care provider, can make a powerful impact on feeling supported and affirmed.
Furthermore, inform your TGD youth of their right to confidentiality. Many TGD youth may not be out to their parents, and you may be the first person to whom they disclosed their gender identity. This is especially helpful if you describe their right to and the limits of confidentiality (e.g., suicidality) at the beginning of the visit. Assurance of confidentiality is a vital reason adolescents and young adults seek health care from a medical provider,5 and the same can be said of TGD youth; however, keep in mind that if they do desire to transition using cross-sex hormones or surgery, parental permission is required.
If they are not out to their parents and they are planning to come out to their parents, offer to be there when they do. Having someone to support the child – someone who is a medical provider – can add to the sense of legitimacy that what the child is experiencing is normal and healthy. Providing guidance on how parents can support their TGD child is essential for successful affirmation, and some suggestions can be found in an LGBT Youth Consult column I wrote titled, “Guidance for parents of LGBT youth.”
If you practice in a location where the nearest expert in gender-affirming care can be hundreds of miles away, educate yourself on gender-affirming care. Several guidelines are available. The World Professional Society for Transgender Standards of Care (SOC) focuses on the mental health aspects of gender-affirming care. The SOC recommends, but no longer requires, letters from a mental health therapist to start gender-affirming medical treatments and does allow for a discussion between you and the patient on the risks, benefits, alternatives, unknowns, limitations of treatment, and risks of not treating (i.e., obtaining informed consent) as the threshold for hormone therapy.6 This approach, known as the “informed consent model,” can be helpful in expanding health care access for TGD youth. Furthermore, there’s the Endocrine Society Clinical Practice Guidelines7 and the University of California, San Francisco, Guidelines,8 which focus on the medical aspects of gender-affirming care, such as when to start pubertal blockers and dosing for cross-sex hormones. Finally, there are resources that allow providers to consult an expert remotely for more complicated cases. Transline is a transgender medical consultation service staffed by medical providers with expertise in gender-affirming care. Providers can learn more about this valuable service on the website: http://project-health.org/transline/.
Working in a major medical center is not necessary in providing gender-affirming care to TGD youth. Being respectful, supportive, and having the willingness to learn are the minimal requirements. Resources are available to help guide you on the more technical aspects of gender-affirming care. Maintaining a supportive environment and using these resources will help you expand health care access for this population.
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@mdedge.com.
References
1. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
2. Psychol Bull. 2003 Sep;129(5):674-97.
3. “Creating an LGBTQ-friendly practice,” American Medical Association.
4. Fenway Health Client Registration Form.
5. JAMA. 1993 Mar 17;269(11):1404-7.
6. Int J Transgenderism 2012;13:165-232.
7. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-903.
8. “Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People,” 2nd edition (San Francisco, CA: University of California, San Francisco, June 17, 2016).
I am privileged to work in a university hospital system where I have access to colleagues with expertise in LGBT health; however, medical providers in the community may not enjoy such resources. Many transgender and gender-diverse (TGD) youth now are seeking help from their community primary care providers to affirm their gender identity, but many community primary care providers do not have the luxury of referring these patients to an expert in gender-affirming care when their TGD patients express the desire to affirm their gender through medical and surgical means. This is even more difficult if the nearest referral center is hundreds of miles away. Nevertheless,
If a TGD youth discloses their gender identity to you, it is critical that you make the patient feel safe and supported. Showing support is important in maintaining rapport between you and the patient. Furthermore, you may be one of the very few adults in the child’s life whom they can trust.
First of all, thank them. For many TGD patients, disclosing their gender identity to a health care provider can be a herculean task. They may have spent many hours trying to find the right words to say to disclose an important aspect of themselves to you. They also probably spent a fair amount of time worrying about whether or not you would react positively to this disclosure. This fear is reasonable. About one-fifth of transgender people have reported being kicked out of a medical practice because of their disclosure of their gender identity.1
Secondly, assure the TGD patient that your treatment would be no different from the care provided for other patients. Discrimination from a health care provider has frequently been reported by TGD patients1 and is expected from this population.2 By emphasizing this, you have signaled to them that you are committed to treating them with dignity and respect. Furthermore, signal your commitment to this treatment by making the clinic a safe and welcoming place for LGBT youth. Several resources exist that can help with this. The American Medical Association provides a good example on how to draft a nondiscrimination statement that can be posted in waiting areas;3 the Fenway Institute has a good example of an intake form that is LGBT friendly.4
In addition, a good way to help affirm their gender identity is to tell them that being transgender or gender-diverse is normal and healthy. Many times, TGD youth will hear narratives that gender diversity is pathological or aberrant; however, hearing that they are healthy and normal, especially from a health care provider, can make a powerful impact on feeling supported and affirmed.
Furthermore, inform your TGD youth of their right to confidentiality. Many TGD youth may not be out to their parents, and you may be the first person to whom they disclosed their gender identity. This is especially helpful if you describe their right to and the limits of confidentiality (e.g., suicidality) at the beginning of the visit. Assurance of confidentiality is a vital reason adolescents and young adults seek health care from a medical provider,5 and the same can be said of TGD youth; however, keep in mind that if they do desire to transition using cross-sex hormones or surgery, parental permission is required.
If they are not out to their parents and they are planning to come out to their parents, offer to be there when they do. Having someone to support the child – someone who is a medical provider – can add to the sense of legitimacy that what the child is experiencing is normal and healthy. Providing guidance on how parents can support their TGD child is essential for successful affirmation, and some suggestions can be found in an LGBT Youth Consult column I wrote titled, “Guidance for parents of LGBT youth.”
If you practice in a location where the nearest expert in gender-affirming care can be hundreds of miles away, educate yourself on gender-affirming care. Several guidelines are available. The World Professional Society for Transgender Standards of Care (SOC) focuses on the mental health aspects of gender-affirming care. The SOC recommends, but no longer requires, letters from a mental health therapist to start gender-affirming medical treatments and does allow for a discussion between you and the patient on the risks, benefits, alternatives, unknowns, limitations of treatment, and risks of not treating (i.e., obtaining informed consent) as the threshold for hormone therapy.6 This approach, known as the “informed consent model,” can be helpful in expanding health care access for TGD youth. Furthermore, there’s the Endocrine Society Clinical Practice Guidelines7 and the University of California, San Francisco, Guidelines,8 which focus on the medical aspects of gender-affirming care, such as when to start pubertal blockers and dosing for cross-sex hormones. Finally, there are resources that allow providers to consult an expert remotely for more complicated cases. Transline is a transgender medical consultation service staffed by medical providers with expertise in gender-affirming care. Providers can learn more about this valuable service on the website: http://project-health.org/transline/.
Working in a major medical center is not necessary in providing gender-affirming care to TGD youth. Being respectful, supportive, and having the willingness to learn are the minimal requirements. Resources are available to help guide you on the more technical aspects of gender-affirming care. Maintaining a supportive environment and using these resources will help you expand health care access for this population.
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@mdedge.com.
References
1. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
2. Psychol Bull. 2003 Sep;129(5):674-97.
3. “Creating an LGBTQ-friendly practice,” American Medical Association.
4. Fenway Health Client Registration Form.
5. JAMA. 1993 Mar 17;269(11):1404-7.
6. Int J Transgenderism 2012;13:165-232.
7. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-903.
8. “Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People,” 2nd edition (San Francisco, CA: University of California, San Francisco, June 17, 2016).
Clinical research in private practice? It can be done, and here’s how
Not every physician coming out of medical school wants to go down the path of conducting clinical research. But for those who do, the decision is a rewarding one that can make a real difference in patients’ lives.
I took a nontraditional route to get to my current role as the director of clinical research and education at the largest gastroenterology practice in the United States. I had a business degree coming out of college and worked for years in the business world prior to going to medical school. After graduation, I got an offer to join the pharmaceutical industry in medical affairs. There, I focused on inflammatory bowel disease (IBD), where my role was to share high-level scientific data and liaise with IBD disease state experts. Part of the role was working internally with clinical operations and externally with sites conducting research throughout the United States. In the next 6 years, I had the opportunity to observe how research was run in both the academic and community practice settings, noting those characteristics that allowed some to succeed and far more to stagnate or fail.
In 2014, I joined Texas Digestive Disease Consultants with the goal to ramp up the practice’s clinical research arm and create a department expressly for that purpose. To date, the department has become incredibly successful and ultimately sustainable. If you’re considering joining a practice based on its clinical research program or starting one in your current practice, here is what I’ve learned along the way:
Know the benefit to patients
You have to decide to conduct clinical research because of its benefit to the patient, not because you see it as an alternative revenue stream. It will never be sustainable if viewed as a profit center. Clinical research offers therapeutic advancements that will not be available to most for the next 5-10 years. Additionally, patients do not need insurance in order to participate in a study. The sponsor covers all study visits, procedures, and therapeutics.
Know the value to the practice
Having a clinical trials program brings both direct and indirect enterprise value to the practice. It may come in the form of referrals from other practices that don’t have the same capabilities. Patients may view your practice differently, knowing that it has the added value of research. There is a halo effect from having clinical trials capabilities in how you are viewed by patients and other physicians in the community.
Get the right people in place
First, you will need an enthusiastic primary investigator who can take a bit of time from practice to conduct clinical trials. But just as importantly, you need a knowledgeable clinical research coordinator. Without an effective coordinator, the program is doomed. A good coordinator should be well rounded in all aspects of research (e.g., regulatory, patient recruitment, quality assurance, contracts, budgets, running labs, conducting patient visits) and able to deal with the day-to-day intricacies of running clinical trials, which will allow a doctor to take care of the existing practice. They should also be versed in the requisite equipment (e.g., locking refrigerator, freezer, and ambient cabinet, temperature monitoring devices, EKG machine, and centrifuge) necessary to run a clinical study.
Know how to recruit patients
The database at Texas Digestive Disease Consultants/GI Alliance (TDDC/GIA) is vast, which makes identification of patients who may qualify for a trial an easier task. Many practices will have an electronic medical record that will aid in identification, but if that is not the case at your practice, there are a number of ways you can go about this. First, talk to physicians in your practice and in other practices – internists, family physicians, and other gastroenterologists come to mind – about what you can offer. Send a letter or an email out to physicians in the community with the inclusion/exclusion criteria for your study, and always direct them to https://clinicaltrials.gov/ for additional information. Patient advocacy organizations are another good source of referrals for clinical trials. And of course, pharmaceutical companies have recruitment services that they use and can help steer patients your way.
Understand the ethics
There are numerous ethical and legal considerations when it comes to running clinical trials. The principles of Good Clinical Practice (GCP) and Human Subject Protection (HSP) guide the conduct of clinical trials in the United States. Understanding the concepts and regulations around caring for patients in trials is not only “good practice,” it’s a necessity. There are free Good Clinical Practice training courses available, which are required every few years for everyone conducting clinical research. These courses are quite lengthy (3-6 hours), but provide a great overview of the Food and Drug Administration regulations, ethical considerations, and other advice on successfully operating a clinical trials program. Again, a capable clinical research coordinator will help guide you here.
Adopt standard operating procedures
Every clinical trials sponsor will require standard operating procedures for such facets of research as informed consent, reporting requirements, and safety monitoring. Here again, a seasoned clinical trials coordinator can put you on the right path. You may choose to purchase standardized templates or work with another group that already has them and would be willing to share.
Be smart about spending
While this may depend on the scale you want to grow your research, at TDDC/GIA we knew we wanted to build a sustainable program. We invested a lot of time and money into our infrastructure, as well as adopting a robust Clinical Trials Management System (CTMS). A CTMS system will provide the ability to measure productivity, finances, schedule patient visits, and pay patient stipends. Some systems even automate the regulatory process (E-Regulatory) or source process (E-source), which can cut down on the paper burden on a site.
Seek mentors
Look for someone to emulate who is already established in operating a clinical research program in private practice. Reach out to the practices or physicians that are already doing this work and doing it well. For physicians who are just starting out or still in training, look for opportunities to publish or be involved with the clinical trials program at your institution.
Contacts in the pharmaceutical industry are very important to getting a new program off the ground. Ask the pharma sales representatives who visit your clinic to put you in touch with their medical science liaison (MSL). The MSL can get you information about the clinical trials their company is currently running and those they have in the pipeline.
Dr. Chris Fourment, director of clinical research and education, Texas Digestive Disease Consultants/GI Alliance.
Not every physician coming out of medical school wants to go down the path of conducting clinical research. But for those who do, the decision is a rewarding one that can make a real difference in patients’ lives.
I took a nontraditional route to get to my current role as the director of clinical research and education at the largest gastroenterology practice in the United States. I had a business degree coming out of college and worked for years in the business world prior to going to medical school. After graduation, I got an offer to join the pharmaceutical industry in medical affairs. There, I focused on inflammatory bowel disease (IBD), where my role was to share high-level scientific data and liaise with IBD disease state experts. Part of the role was working internally with clinical operations and externally with sites conducting research throughout the United States. In the next 6 years, I had the opportunity to observe how research was run in both the academic and community practice settings, noting those characteristics that allowed some to succeed and far more to stagnate or fail.
In 2014, I joined Texas Digestive Disease Consultants with the goal to ramp up the practice’s clinical research arm and create a department expressly for that purpose. To date, the department has become incredibly successful and ultimately sustainable. If you’re considering joining a practice based on its clinical research program or starting one in your current practice, here is what I’ve learned along the way:
Know the benefit to patients
You have to decide to conduct clinical research because of its benefit to the patient, not because you see it as an alternative revenue stream. It will never be sustainable if viewed as a profit center. Clinical research offers therapeutic advancements that will not be available to most for the next 5-10 years. Additionally, patients do not need insurance in order to participate in a study. The sponsor covers all study visits, procedures, and therapeutics.
Know the value to the practice
Having a clinical trials program brings both direct and indirect enterprise value to the practice. It may come in the form of referrals from other practices that don’t have the same capabilities. Patients may view your practice differently, knowing that it has the added value of research. There is a halo effect from having clinical trials capabilities in how you are viewed by patients and other physicians in the community.
Get the right people in place
First, you will need an enthusiastic primary investigator who can take a bit of time from practice to conduct clinical trials. But just as importantly, you need a knowledgeable clinical research coordinator. Without an effective coordinator, the program is doomed. A good coordinator should be well rounded in all aspects of research (e.g., regulatory, patient recruitment, quality assurance, contracts, budgets, running labs, conducting patient visits) and able to deal with the day-to-day intricacies of running clinical trials, which will allow a doctor to take care of the existing practice. They should also be versed in the requisite equipment (e.g., locking refrigerator, freezer, and ambient cabinet, temperature monitoring devices, EKG machine, and centrifuge) necessary to run a clinical study.
Know how to recruit patients
The database at Texas Digestive Disease Consultants/GI Alliance (TDDC/GIA) is vast, which makes identification of patients who may qualify for a trial an easier task. Many practices will have an electronic medical record that will aid in identification, but if that is not the case at your practice, there are a number of ways you can go about this. First, talk to physicians in your practice and in other practices – internists, family physicians, and other gastroenterologists come to mind – about what you can offer. Send a letter or an email out to physicians in the community with the inclusion/exclusion criteria for your study, and always direct them to https://clinicaltrials.gov/ for additional information. Patient advocacy organizations are another good source of referrals for clinical trials. And of course, pharmaceutical companies have recruitment services that they use and can help steer patients your way.
Understand the ethics
There are numerous ethical and legal considerations when it comes to running clinical trials. The principles of Good Clinical Practice (GCP) and Human Subject Protection (HSP) guide the conduct of clinical trials in the United States. Understanding the concepts and regulations around caring for patients in trials is not only “good practice,” it’s a necessity. There are free Good Clinical Practice training courses available, which are required every few years for everyone conducting clinical research. These courses are quite lengthy (3-6 hours), but provide a great overview of the Food and Drug Administration regulations, ethical considerations, and other advice on successfully operating a clinical trials program. Again, a capable clinical research coordinator will help guide you here.
Adopt standard operating procedures
Every clinical trials sponsor will require standard operating procedures for such facets of research as informed consent, reporting requirements, and safety monitoring. Here again, a seasoned clinical trials coordinator can put you on the right path. You may choose to purchase standardized templates or work with another group that already has them and would be willing to share.
Be smart about spending
While this may depend on the scale you want to grow your research, at TDDC/GIA we knew we wanted to build a sustainable program. We invested a lot of time and money into our infrastructure, as well as adopting a robust Clinical Trials Management System (CTMS). A CTMS system will provide the ability to measure productivity, finances, schedule patient visits, and pay patient stipends. Some systems even automate the regulatory process (E-Regulatory) or source process (E-source), which can cut down on the paper burden on a site.
Seek mentors
Look for someone to emulate who is already established in operating a clinical research program in private practice. Reach out to the practices or physicians that are already doing this work and doing it well. For physicians who are just starting out or still in training, look for opportunities to publish or be involved with the clinical trials program at your institution.
Contacts in the pharmaceutical industry are very important to getting a new program off the ground. Ask the pharma sales representatives who visit your clinic to put you in touch with their medical science liaison (MSL). The MSL can get you information about the clinical trials their company is currently running and those they have in the pipeline.
Dr. Chris Fourment, director of clinical research and education, Texas Digestive Disease Consultants/GI Alliance.
Not every physician coming out of medical school wants to go down the path of conducting clinical research. But for those who do, the decision is a rewarding one that can make a real difference in patients’ lives.
I took a nontraditional route to get to my current role as the director of clinical research and education at the largest gastroenterology practice in the United States. I had a business degree coming out of college and worked for years in the business world prior to going to medical school. After graduation, I got an offer to join the pharmaceutical industry in medical affairs. There, I focused on inflammatory bowel disease (IBD), where my role was to share high-level scientific data and liaise with IBD disease state experts. Part of the role was working internally with clinical operations and externally with sites conducting research throughout the United States. In the next 6 years, I had the opportunity to observe how research was run in both the academic and community practice settings, noting those characteristics that allowed some to succeed and far more to stagnate or fail.
In 2014, I joined Texas Digestive Disease Consultants with the goal to ramp up the practice’s clinical research arm and create a department expressly for that purpose. To date, the department has become incredibly successful and ultimately sustainable. If you’re considering joining a practice based on its clinical research program or starting one in your current practice, here is what I’ve learned along the way:
Know the benefit to patients
You have to decide to conduct clinical research because of its benefit to the patient, not because you see it as an alternative revenue stream. It will never be sustainable if viewed as a profit center. Clinical research offers therapeutic advancements that will not be available to most for the next 5-10 years. Additionally, patients do not need insurance in order to participate in a study. The sponsor covers all study visits, procedures, and therapeutics.
Know the value to the practice
Having a clinical trials program brings both direct and indirect enterprise value to the practice. It may come in the form of referrals from other practices that don’t have the same capabilities. Patients may view your practice differently, knowing that it has the added value of research. There is a halo effect from having clinical trials capabilities in how you are viewed by patients and other physicians in the community.
Get the right people in place
First, you will need an enthusiastic primary investigator who can take a bit of time from practice to conduct clinical trials. But just as importantly, you need a knowledgeable clinical research coordinator. Without an effective coordinator, the program is doomed. A good coordinator should be well rounded in all aspects of research (e.g., regulatory, patient recruitment, quality assurance, contracts, budgets, running labs, conducting patient visits) and able to deal with the day-to-day intricacies of running clinical trials, which will allow a doctor to take care of the existing practice. They should also be versed in the requisite equipment (e.g., locking refrigerator, freezer, and ambient cabinet, temperature monitoring devices, EKG machine, and centrifuge) necessary to run a clinical study.
Know how to recruit patients
The database at Texas Digestive Disease Consultants/GI Alliance (TDDC/GIA) is vast, which makes identification of patients who may qualify for a trial an easier task. Many practices will have an electronic medical record that will aid in identification, but if that is not the case at your practice, there are a number of ways you can go about this. First, talk to physicians in your practice and in other practices – internists, family physicians, and other gastroenterologists come to mind – about what you can offer. Send a letter or an email out to physicians in the community with the inclusion/exclusion criteria for your study, and always direct them to https://clinicaltrials.gov/ for additional information. Patient advocacy organizations are another good source of referrals for clinical trials. And of course, pharmaceutical companies have recruitment services that they use and can help steer patients your way.
Understand the ethics
There are numerous ethical and legal considerations when it comes to running clinical trials. The principles of Good Clinical Practice (GCP) and Human Subject Protection (HSP) guide the conduct of clinical trials in the United States. Understanding the concepts and regulations around caring for patients in trials is not only “good practice,” it’s a necessity. There are free Good Clinical Practice training courses available, which are required every few years for everyone conducting clinical research. These courses are quite lengthy (3-6 hours), but provide a great overview of the Food and Drug Administration regulations, ethical considerations, and other advice on successfully operating a clinical trials program. Again, a capable clinical research coordinator will help guide you here.
Adopt standard operating procedures
Every clinical trials sponsor will require standard operating procedures for such facets of research as informed consent, reporting requirements, and safety monitoring. Here again, a seasoned clinical trials coordinator can put you on the right path. You may choose to purchase standardized templates or work with another group that already has them and would be willing to share.
Be smart about spending
While this may depend on the scale you want to grow your research, at TDDC/GIA we knew we wanted to build a sustainable program. We invested a lot of time and money into our infrastructure, as well as adopting a robust Clinical Trials Management System (CTMS). A CTMS system will provide the ability to measure productivity, finances, schedule patient visits, and pay patient stipends. Some systems even automate the regulatory process (E-Regulatory) or source process (E-source), which can cut down on the paper burden on a site.
Seek mentors
Look for someone to emulate who is already established in operating a clinical research program in private practice. Reach out to the practices or physicians that are already doing this work and doing it well. For physicians who are just starting out or still in training, look for opportunities to publish or be involved with the clinical trials program at your institution.
Contacts in the pharmaceutical industry are very important to getting a new program off the ground. Ask the pharma sales representatives who visit your clinic to put you in touch with their medical science liaison (MSL). The MSL can get you information about the clinical trials their company is currently running and those they have in the pipeline.
Dr. Chris Fourment, director of clinical research and education, Texas Digestive Disease Consultants/GI Alliance.
Pneumonia with tender, dry, crusted lips
Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”
Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.
EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.
SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.1 SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.
MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.2 Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.
Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.
The differential diagnosis between RIME/MIRM, SJS, and TEN may be difficult to distinguish in the first few days of presentation, and consideration of infections and possible medication causes is important. DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) also is in the differential diagnosis. DRESS usually has a long latency (2-8 weeks) between drug exposure and disease onset.
Treatment of RIME/MIRM is supportive care and treatment of any underlying infection. Steroids and intravenous immune globulin (IVIG) have been used to treat reactive mucositis, as well as cyclosporine and biologic agents (such as etanercept), in an attempt to minimize the extent and duration of mucous membrane vesiculation and denudation. While these drugs may help shorten the duration of the disease course, controlled trials are lacking and there is little comparative literature on efficacy or safety of these agents.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at pdnews@mdedge.com.
References
1. Arch Dermatol. 1993 Jan;129(1):92-6.
2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.
Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”
Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.
EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.
SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.1 SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.
MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.2 Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.
Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.
The differential diagnosis between RIME/MIRM, SJS, and TEN may be difficult to distinguish in the first few days of presentation, and consideration of infections and possible medication causes is important. DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) also is in the differential diagnosis. DRESS usually has a long latency (2-8 weeks) between drug exposure and disease onset.
Treatment of RIME/MIRM is supportive care and treatment of any underlying infection. Steroids and intravenous immune globulin (IVIG) have been used to treat reactive mucositis, as well as cyclosporine and biologic agents (such as etanercept), in an attempt to minimize the extent and duration of mucous membrane vesiculation and denudation. While these drugs may help shorten the duration of the disease course, controlled trials are lacking and there is little comparative literature on efficacy or safety of these agents.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at pdnews@mdedge.com.
References
1. Arch Dermatol. 1993 Jan;129(1):92-6.
2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.
Mycoplasma pneumoniae infection commonly manifests as an upper or lower respiratory tract infection with associated fever, dyspnea, cough, and coryza. However, patients can present with extrapulmonary complications with dermatologic findings including mucocutaneous eruptions. M. pneumoniae–associated mucocutaneous disease has prominent mucositis and typically sparse cutaneous involvement. The mucositis usually involves the lips and oral mucosa, eye conjunctivae, and nasal mucosa and can involve urogenital lesions. It predominantly is observed in children and adolescents. This condition is essentially a subtype of Stevens-Johnson syndrome, with a specific infection-associated etiology, and has been called “Mycoplasma pneumoniae–induced rash and mucositis,” shortened to “MIRM.”
Severe reactive mucocutaneous eruptions include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). While there has been semantic confusion over the years, there are some distinctive characteristics.
EM is characterized by typical three-ringed target papules that are predominantly acral in location and often without mucosal involvement. The lesions are “multiforme” in that they can appear polymorphous and evolve during an episode, with erythematous macules progressing to edematous papules, sometimes with a halo of pallor and concentric “target-like” appearance. Lesions of EM are fixed, meaning individual lesions last 7-10 days, unlike urticarial lesions that last hours. EM classically is associated with herpes simplex virus infections which usually precede its development.
SJS and TEN display atypical macules and papules which develop into erythematous vesicles, bullae, and potentially extensive desquamation, usually presenting with fever and systemic symptoms, with multiple mucosal sites involved. SJS usually is defined by having bullae restricted to less than 10% of body surface area (BSA), TEN as greater than 30% BSA, and “overlap SJS-TEN” as 20%-30% skin detachment.1 SJS and TEN commonly are induced by medications and on a spectrum of drug hypersensitivity–induced epidermal necrolysis.
MIRM has been highlighted as a distinct, common condition, usually mucous-membrane predominant with involvement of two or more mucosal sites, less than 10% total BSA, the presence of few vesiculobullous lesions or scattered atypical targets with or without targetoid lesions (without rash is called MIRM sine rash), and clinical and laboratory evidence of atypical pneumonia.2 Other infections can cause similar eruptions (for example, Chlamydia pneumoniae), and a recent proposal by the Pediatric Dermatology Research Alliance has suggested the term “Reactive Infectious Mucocutaneous Eruption” (RIME) to include MIRM and other infection-induced reactions.
Laboratory diagnosis of M. pneumoniae is via serology or polymerase chain reaction. Antibody titers begin to rise approximately 7-9 days after infection and peak at 3-4 weeks. Enzyme immunoassay is more sensitive in detecting acute infection than culture and has sensitivity comparable to the polymerase chain reaction if there has been sufficient time to develop an antibody response.
The differential diagnosis between RIME/MIRM, SJS, and TEN may be difficult to distinguish in the first few days of presentation, and consideration of infections and possible medication causes is important. DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) also is in the differential diagnosis. DRESS usually has a long latency (2-8 weeks) between drug exposure and disease onset.
Treatment of RIME/MIRM is supportive care and treatment of any underlying infection. Steroids and intravenous immune globulin (IVIG) have been used to treat reactive mucositis, as well as cyclosporine and biologic agents (such as etanercept), in an attempt to minimize the extent and duration of mucous membrane vesiculation and denudation. While these drugs may help shorten the duration of the disease course, controlled trials are lacking and there is little comparative literature on efficacy or safety of these agents.
Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. They said they have no financial disclosures. Email Dr. Eichenfield and Dr. Bhatti at pdnews@mdedge.com.
References
1. Arch Dermatol. 1993 Jan;129(1):92-6.
2. J Am Acad Dermatol. 2015 Feb;72(2):239-45.
Long-term survival in stage IV NSCLC
In this edition of “How I will treat my next patient,” I highlight two studies addressing long-term survival for patients with stage IV non–small cell lung cancer (NSCLC). One summarizes survival of patients who received nivolumab therapy in the second- or later-line setting. The other is a retrospective database query regarding whether local consolidation (LC) improves survival after systemic treatment of patients with oligometastatic NSCLC.
Nivolumab therapy
Scott J. Antonia, MD, PhD, and colleagues sought to determine the frequency of long-term survival among advanced NSCLC patients who received nivolumab in the second-line or later settings (Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045[19]30407-3). They aggregated the results of four trials. Checkmate 017 and 057 were phase 3 comparisons of nivolumab with docetaxel for nonsquamous and squamous NSCLC, respectively – with crossover from docetaxel to nivolumab permitted. Checkmate 003 was a dose-escalation trial and Checkmate 063 was a phase 2 study of nivolumab in advanced, refractory squamous NSCLC. A minimum follow-up of 4 years was required.
In total, 664 patients participated in the four trials, more than 85% of whom received the fairly standard dose of 3 mg/kg every 2 weeks. In a very data-dense analysis, among all patients who received nivolumab, the 4-year overall survival was 14% (95% confidence interval, 11%-17%). Four-year overall survival was higher (19%; 95% CI, 15%-24%) in patients with at least 1% programmed death-ligand 1 (PD-L1) expression. There was no difference by histology (squamous vs. nonsquamous). Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, PD-L1 greater than 10%, and absence of liver metastases were more likely to achieve 4-year overall survival.
Although progression-free survival was low (8%, overall; 19% for patients achieving complete remission or partial remission), depth of response correlated with the 4-year overall survival rate. Those patients in complete or partial remission at 6 months had an overall survival at 4 years of 56%. Stable disease at 6 months showed an overall survival at 4 years of 19%, which was superior to the results for patients with partial disease as best response (4%).
There were two treatment-related deaths with nivolumab, with no unexpected safety signals. Despite allowing continuous treatment in three of the four studies, most potentially immune-related toxic events occurred in the first 2-3 years of therapy. In the two randomized studies (017 and 057), 4-year overall survival was higher with nivolumab (14%) than with docetaxel (5%), with no overlap in the 95% confidence intervals.
What this means in practice
British prime minister, Benjamin Disraeli (and, later, Mark Twain) said, “There are three kinds of lies: lies, damned lies, and statistics.” There are no lies in Dr. Antonia’s paper, but there are plenty of statistics – which oncologists love. The reported data enable us to put some boundaries on the figures we quote when patients ask us, “How well could I do with this treatment?” Dr. Antonia’s paper significantly assists with these very practical discussions. For patients who want more detail, the boundaries can be further refined. Dr. Antonia and colleagues have given us clinical (depth of response, performance status, sites of metastasis) and molecular (proportion of cells with PD-L1) refinements to personalize our consultations with patients.
Unfortunately, the data do not allow us to predict who should not receive an immune checkpoint inhibitor and, instead, receive late-line chemotherapy or early hospice referral. The data summarize well-executed clinical trials, but it is well known that (as reported at the Quality Care Symposium 2019) NSCLC patients participating in clinical trials have significantly improved survival rates – perhaps as much as two times – compared with those not enrolled in trials. These realities, however, should not obscure the fact that immune checkpoint inhibitors are a major advance for metastatic NSCLC patients, including those who have progressed after prior treatment. They offer hope for cancer-free or cancer-controlled survival that would have properly been placed in the category of “a miracle” just a few years ago.
Local consolidation
Johannes Uhlig, MD, and colleagues analyzed 6 years of National Cancer Database records, identifying 34,887 stage IV NSCLC patients who had fewer than two distant metastatic lesions in the liver, lung, brain, or bone (JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702). Treatment groups were divided into patients who received systemic therapy alone (70.3% of the total patients), had surgical resection of the primary site plus systemic therapy (2.4%), or received external beam radiation therapy or thermal ablation (EBRT/TA) of the primary site plus systemic therapy (27.3%). Multivariable Cox proportional hazards models, incorporating a number of clinical variables, were used to compare overall survival between the three groups at a median follow-up of approximately 39 months.
They found that patients treated with surgical consolidation had a 41% lower mortality, in comparison with systemic therapy alone. EBRT/TA was also associated with lower mortality (by 5%), in comparison with systemic therapy alone, but the benefit was more nuanced. For instance, patients with squamous cell histology with low tumor bulk, low nodal burden, and fewer distant sites of disease benefited, but patients with adenocarcinoma and bulkier disease or more than two distant sites did not benefit.
The discussion emphasized all of the caveats that would be appropriate for a retrospective, telescopic record review – patient selection factors; lack of detail about systemic therapy; small numbers of patients in various subsets; exclusion of patients who had consolidative treatment of metastatic sites; and the potential for unbalanced allocation of patients with various actionable, prognostically relevant mutations. Further research, including ongoing trials such as NRG-LU002, was encouraged.
How these results influence clinical practice
Ralph R. Weichselbaum, MD, in his Karnofsky lecture at the 2018 annual meeting of the American Society of Clinical Oncology highlighted the hypothesis that metastatic tumors are enriched differentially for oligometastatic or polymetastatic miRNAs and that these miRNAs could influence future clinical behavior (J Clin Oncol. 2018;36[32]:3240-50). This work, coupled with clinical features (number of sites of disease, pace of progression) could elucidate which oligometastatic NSCLC patients might benefit from aggressive local treatment and achieve long-term, disease-free survival.
As previously reported, Daniel R. Gomez, MD, and colleagues found improved median progression-free survival (14.2 vs. 4.4 months; P = .022) and overall survival (41.2 vs. 17.0 months; P = .017) among patients with oligometastatic NSCLC who were randomized to local consolidation versus standard maintenance therapy/observation (J Clin Oncol. 8 May 2019. doi: 10. 1200/JCO.19.00201). Joshua M. Bauml and colleagues reported impressive results for systemically treated stage IV NSCLC patients who received local consolidation and checkpoint inhibitors for “oligo-remnant disease” (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449).
At the present time, clinical practice should remain governed by the general tendency to discourage aggressive local treatment except in highly selected cases with poorly resolved or impending life-altering symptoms. The publication by Dr. Uhlig and colleagues and the previously reported phase 2 trials, support phase 3 randomized trials of local treatment of isolated sites in oligometastatic NSCLC patients, particularly in an era of immune-based systemic treatment that offers finite potential for long-term survival.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I highlight two studies addressing long-term survival for patients with stage IV non–small cell lung cancer (NSCLC). One summarizes survival of patients who received nivolumab therapy in the second- or later-line setting. The other is a retrospective database query regarding whether local consolidation (LC) improves survival after systemic treatment of patients with oligometastatic NSCLC.
Nivolumab therapy
Scott J. Antonia, MD, PhD, and colleagues sought to determine the frequency of long-term survival among advanced NSCLC patients who received nivolumab in the second-line or later settings (Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045[19]30407-3). They aggregated the results of four trials. Checkmate 017 and 057 were phase 3 comparisons of nivolumab with docetaxel for nonsquamous and squamous NSCLC, respectively – with crossover from docetaxel to nivolumab permitted. Checkmate 003 was a dose-escalation trial and Checkmate 063 was a phase 2 study of nivolumab in advanced, refractory squamous NSCLC. A minimum follow-up of 4 years was required.
In total, 664 patients participated in the four trials, more than 85% of whom received the fairly standard dose of 3 mg/kg every 2 weeks. In a very data-dense analysis, among all patients who received nivolumab, the 4-year overall survival was 14% (95% confidence interval, 11%-17%). Four-year overall survival was higher (19%; 95% CI, 15%-24%) in patients with at least 1% programmed death-ligand 1 (PD-L1) expression. There was no difference by histology (squamous vs. nonsquamous). Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, PD-L1 greater than 10%, and absence of liver metastases were more likely to achieve 4-year overall survival.
Although progression-free survival was low (8%, overall; 19% for patients achieving complete remission or partial remission), depth of response correlated with the 4-year overall survival rate. Those patients in complete or partial remission at 6 months had an overall survival at 4 years of 56%. Stable disease at 6 months showed an overall survival at 4 years of 19%, which was superior to the results for patients with partial disease as best response (4%).
There were two treatment-related deaths with nivolumab, with no unexpected safety signals. Despite allowing continuous treatment in three of the four studies, most potentially immune-related toxic events occurred in the first 2-3 years of therapy. In the two randomized studies (017 and 057), 4-year overall survival was higher with nivolumab (14%) than with docetaxel (5%), with no overlap in the 95% confidence intervals.
What this means in practice
British prime minister, Benjamin Disraeli (and, later, Mark Twain) said, “There are three kinds of lies: lies, damned lies, and statistics.” There are no lies in Dr. Antonia’s paper, but there are plenty of statistics – which oncologists love. The reported data enable us to put some boundaries on the figures we quote when patients ask us, “How well could I do with this treatment?” Dr. Antonia’s paper significantly assists with these very practical discussions. For patients who want more detail, the boundaries can be further refined. Dr. Antonia and colleagues have given us clinical (depth of response, performance status, sites of metastasis) and molecular (proportion of cells with PD-L1) refinements to personalize our consultations with patients.
Unfortunately, the data do not allow us to predict who should not receive an immune checkpoint inhibitor and, instead, receive late-line chemotherapy or early hospice referral. The data summarize well-executed clinical trials, but it is well known that (as reported at the Quality Care Symposium 2019) NSCLC patients participating in clinical trials have significantly improved survival rates – perhaps as much as two times – compared with those not enrolled in trials. These realities, however, should not obscure the fact that immune checkpoint inhibitors are a major advance for metastatic NSCLC patients, including those who have progressed after prior treatment. They offer hope for cancer-free or cancer-controlled survival that would have properly been placed in the category of “a miracle” just a few years ago.
Local consolidation
Johannes Uhlig, MD, and colleagues analyzed 6 years of National Cancer Database records, identifying 34,887 stage IV NSCLC patients who had fewer than two distant metastatic lesions in the liver, lung, brain, or bone (JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702). Treatment groups were divided into patients who received systemic therapy alone (70.3% of the total patients), had surgical resection of the primary site plus systemic therapy (2.4%), or received external beam radiation therapy or thermal ablation (EBRT/TA) of the primary site plus systemic therapy (27.3%). Multivariable Cox proportional hazards models, incorporating a number of clinical variables, were used to compare overall survival between the three groups at a median follow-up of approximately 39 months.
They found that patients treated with surgical consolidation had a 41% lower mortality, in comparison with systemic therapy alone. EBRT/TA was also associated with lower mortality (by 5%), in comparison with systemic therapy alone, but the benefit was more nuanced. For instance, patients with squamous cell histology with low tumor bulk, low nodal burden, and fewer distant sites of disease benefited, but patients with adenocarcinoma and bulkier disease or more than two distant sites did not benefit.
The discussion emphasized all of the caveats that would be appropriate for a retrospective, telescopic record review – patient selection factors; lack of detail about systemic therapy; small numbers of patients in various subsets; exclusion of patients who had consolidative treatment of metastatic sites; and the potential for unbalanced allocation of patients with various actionable, prognostically relevant mutations. Further research, including ongoing trials such as NRG-LU002, was encouraged.
How these results influence clinical practice
Ralph R. Weichselbaum, MD, in his Karnofsky lecture at the 2018 annual meeting of the American Society of Clinical Oncology highlighted the hypothesis that metastatic tumors are enriched differentially for oligometastatic or polymetastatic miRNAs and that these miRNAs could influence future clinical behavior (J Clin Oncol. 2018;36[32]:3240-50). This work, coupled with clinical features (number of sites of disease, pace of progression) could elucidate which oligometastatic NSCLC patients might benefit from aggressive local treatment and achieve long-term, disease-free survival.
As previously reported, Daniel R. Gomez, MD, and colleagues found improved median progression-free survival (14.2 vs. 4.4 months; P = .022) and overall survival (41.2 vs. 17.0 months; P = .017) among patients with oligometastatic NSCLC who were randomized to local consolidation versus standard maintenance therapy/observation (J Clin Oncol. 8 May 2019. doi: 10. 1200/JCO.19.00201). Joshua M. Bauml and colleagues reported impressive results for systemically treated stage IV NSCLC patients who received local consolidation and checkpoint inhibitors for “oligo-remnant disease” (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449).
At the present time, clinical practice should remain governed by the general tendency to discourage aggressive local treatment except in highly selected cases with poorly resolved or impending life-altering symptoms. The publication by Dr. Uhlig and colleagues and the previously reported phase 2 trials, support phase 3 randomized trials of local treatment of isolated sites in oligometastatic NSCLC patients, particularly in an era of immune-based systemic treatment that offers finite potential for long-term survival.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I highlight two studies addressing long-term survival for patients with stage IV non–small cell lung cancer (NSCLC). One summarizes survival of patients who received nivolumab therapy in the second- or later-line setting. The other is a retrospective database query regarding whether local consolidation (LC) improves survival after systemic treatment of patients with oligometastatic NSCLC.
Nivolumab therapy
Scott J. Antonia, MD, PhD, and colleagues sought to determine the frequency of long-term survival among advanced NSCLC patients who received nivolumab in the second-line or later settings (Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045[19]30407-3). They aggregated the results of four trials. Checkmate 017 and 057 were phase 3 comparisons of nivolumab with docetaxel for nonsquamous and squamous NSCLC, respectively – with crossover from docetaxel to nivolumab permitted. Checkmate 003 was a dose-escalation trial and Checkmate 063 was a phase 2 study of nivolumab in advanced, refractory squamous NSCLC. A minimum follow-up of 4 years was required.
In total, 664 patients participated in the four trials, more than 85% of whom received the fairly standard dose of 3 mg/kg every 2 weeks. In a very data-dense analysis, among all patients who received nivolumab, the 4-year overall survival was 14% (95% confidence interval, 11%-17%). Four-year overall survival was higher (19%; 95% CI, 15%-24%) in patients with at least 1% programmed death-ligand 1 (PD-L1) expression. There was no difference by histology (squamous vs. nonsquamous). Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, PD-L1 greater than 10%, and absence of liver metastases were more likely to achieve 4-year overall survival.
Although progression-free survival was low (8%, overall; 19% for patients achieving complete remission or partial remission), depth of response correlated with the 4-year overall survival rate. Those patients in complete or partial remission at 6 months had an overall survival at 4 years of 56%. Stable disease at 6 months showed an overall survival at 4 years of 19%, which was superior to the results for patients with partial disease as best response (4%).
There were two treatment-related deaths with nivolumab, with no unexpected safety signals. Despite allowing continuous treatment in three of the four studies, most potentially immune-related toxic events occurred in the first 2-3 years of therapy. In the two randomized studies (017 and 057), 4-year overall survival was higher with nivolumab (14%) than with docetaxel (5%), with no overlap in the 95% confidence intervals.
What this means in practice
British prime minister, Benjamin Disraeli (and, later, Mark Twain) said, “There are three kinds of lies: lies, damned lies, and statistics.” There are no lies in Dr. Antonia’s paper, but there are plenty of statistics – which oncologists love. The reported data enable us to put some boundaries on the figures we quote when patients ask us, “How well could I do with this treatment?” Dr. Antonia’s paper significantly assists with these very practical discussions. For patients who want more detail, the boundaries can be further refined. Dr. Antonia and colleagues have given us clinical (depth of response, performance status, sites of metastasis) and molecular (proportion of cells with PD-L1) refinements to personalize our consultations with patients.
Unfortunately, the data do not allow us to predict who should not receive an immune checkpoint inhibitor and, instead, receive late-line chemotherapy or early hospice referral. The data summarize well-executed clinical trials, but it is well known that (as reported at the Quality Care Symposium 2019) NSCLC patients participating in clinical trials have significantly improved survival rates – perhaps as much as two times – compared with those not enrolled in trials. These realities, however, should not obscure the fact that immune checkpoint inhibitors are a major advance for metastatic NSCLC patients, including those who have progressed after prior treatment. They offer hope for cancer-free or cancer-controlled survival that would have properly been placed in the category of “a miracle” just a few years ago.
Local consolidation
Johannes Uhlig, MD, and colleagues analyzed 6 years of National Cancer Database records, identifying 34,887 stage IV NSCLC patients who had fewer than two distant metastatic lesions in the liver, lung, brain, or bone (JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702). Treatment groups were divided into patients who received systemic therapy alone (70.3% of the total patients), had surgical resection of the primary site plus systemic therapy (2.4%), or received external beam radiation therapy or thermal ablation (EBRT/TA) of the primary site plus systemic therapy (27.3%). Multivariable Cox proportional hazards models, incorporating a number of clinical variables, were used to compare overall survival between the three groups at a median follow-up of approximately 39 months.
They found that patients treated with surgical consolidation had a 41% lower mortality, in comparison with systemic therapy alone. EBRT/TA was also associated with lower mortality (by 5%), in comparison with systemic therapy alone, but the benefit was more nuanced. For instance, patients with squamous cell histology with low tumor bulk, low nodal burden, and fewer distant sites of disease benefited, but patients with adenocarcinoma and bulkier disease or more than two distant sites did not benefit.
The discussion emphasized all of the caveats that would be appropriate for a retrospective, telescopic record review – patient selection factors; lack of detail about systemic therapy; small numbers of patients in various subsets; exclusion of patients who had consolidative treatment of metastatic sites; and the potential for unbalanced allocation of patients with various actionable, prognostically relevant mutations. Further research, including ongoing trials such as NRG-LU002, was encouraged.
How these results influence clinical practice
Ralph R. Weichselbaum, MD, in his Karnofsky lecture at the 2018 annual meeting of the American Society of Clinical Oncology highlighted the hypothesis that metastatic tumors are enriched differentially for oligometastatic or polymetastatic miRNAs and that these miRNAs could influence future clinical behavior (J Clin Oncol. 2018;36[32]:3240-50). This work, coupled with clinical features (number of sites of disease, pace of progression) could elucidate which oligometastatic NSCLC patients might benefit from aggressive local treatment and achieve long-term, disease-free survival.
As previously reported, Daniel R. Gomez, MD, and colleagues found improved median progression-free survival (14.2 vs. 4.4 months; P = .022) and overall survival (41.2 vs. 17.0 months; P = .017) among patients with oligometastatic NSCLC who were randomized to local consolidation versus standard maintenance therapy/observation (J Clin Oncol. 8 May 2019. doi: 10. 1200/JCO.19.00201). Joshua M. Bauml and colleagues reported impressive results for systemically treated stage IV NSCLC patients who received local consolidation and checkpoint inhibitors for “oligo-remnant disease” (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449).
At the present time, clinical practice should remain governed by the general tendency to discourage aggressive local treatment except in highly selected cases with poorly resolved or impending life-altering symptoms. The publication by Dr. Uhlig and colleagues and the previously reported phase 2 trials, support phase 3 randomized trials of local treatment of isolated sites in oligometastatic NSCLC patients, particularly in an era of immune-based systemic treatment that offers finite potential for long-term survival.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
Intense stinging and burning, followed by the development of skin lesions minutes after exposure to a plant
Urticaria from stinging nettle
The stinging nettle (Urtica dioica) is a plant that grows in the United States, Eurasia, Northern Africa, and some parts of South America. It is commonly found in patches along hiking trails and near streams. The leaves are green with a characteristic tapered tip and bear tiny spines or hairs. The spines contain substances such as histamine, serotonin, and acetylcholine. Within seconds of contact with the stinging nettle, sharp stinging and burning will occur. Urticaria and pruritus may appear a few minutes later and may last up to 24 hours. The plant is eaten in some parts of the world and has been used as medicine.
The wood nettle (Laportea canadensis) is a relative of the stinging nettle that often grows in woodlands. Like the stinging nettle, the wood nettle leaves are covered with spines that sting when they come into contact with skin. However, the leaves are shorter and more oval shaped that the stinging nettle, and they lack the tapered tip that is characteristic for the stinging nettle. The reaction from the wood nettle is generally milder than that of the stinging nettle.
Plants can illicit different types of reactions in the skin: urticaria (immunologic and toxin mediated), irritant dermatitis (mechanical and chemical), phototoxic dermatitis (phytophotodermatitis), and allergic contact dermatitis. where anyone coming into contact with the hairs of the plant can be affected. Previous sensitization is not required. The reaction usually occurs immediately after exposure.
The allergic contact dermatitis seen with toxicodendron (poison ivy and poison sumac) appears 48 hours after exposure of a previously sensitized person to the plant. This type of delayed hypersensitivity reaction is known as cell-mediated hypersensitivity. Generally, no reaction is elicited upon the first exposure to the allergen. In fact, it may take years of exposure to allergens for someone to develop an allergic contact dermatitis.
The poison ivy plant can grow anywhere and is characteristically found in “leaves of three.” Skin reactions are often appear as linearly-arranged vesicles a few days after the exposure to the urushiol chemical in the sap of the plant. Poison sumac has red stems with 7-12 green, smooth leaves, and causes a similar skin reaction as poison ivy. It typically grows in wet areas.
Most stings are self-limited. Topical corticosteroid creams may be used if needed.
This case and photo were submitted by Susannah McClain, MD, of Three Rivers Dermatology in Coraopolis, Pa., and Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
Urticaria from stinging nettle
The stinging nettle (Urtica dioica) is a plant that grows in the United States, Eurasia, Northern Africa, and some parts of South America. It is commonly found in patches along hiking trails and near streams. The leaves are green with a characteristic tapered tip and bear tiny spines or hairs. The spines contain substances such as histamine, serotonin, and acetylcholine. Within seconds of contact with the stinging nettle, sharp stinging and burning will occur. Urticaria and pruritus may appear a few minutes later and may last up to 24 hours. The plant is eaten in some parts of the world and has been used as medicine.
The wood nettle (Laportea canadensis) is a relative of the stinging nettle that often grows in woodlands. Like the stinging nettle, the wood nettle leaves are covered with spines that sting when they come into contact with skin. However, the leaves are shorter and more oval shaped that the stinging nettle, and they lack the tapered tip that is characteristic for the stinging nettle. The reaction from the wood nettle is generally milder than that of the stinging nettle.
Plants can illicit different types of reactions in the skin: urticaria (immunologic and toxin mediated), irritant dermatitis (mechanical and chemical), phototoxic dermatitis (phytophotodermatitis), and allergic contact dermatitis. where anyone coming into contact with the hairs of the plant can be affected. Previous sensitization is not required. The reaction usually occurs immediately after exposure.
The allergic contact dermatitis seen with toxicodendron (poison ivy and poison sumac) appears 48 hours after exposure of a previously sensitized person to the plant. This type of delayed hypersensitivity reaction is known as cell-mediated hypersensitivity. Generally, no reaction is elicited upon the first exposure to the allergen. In fact, it may take years of exposure to allergens for someone to develop an allergic contact dermatitis.
The poison ivy plant can grow anywhere and is characteristically found in “leaves of three.” Skin reactions are often appear as linearly-arranged vesicles a few days after the exposure to the urushiol chemical in the sap of the plant. Poison sumac has red stems with 7-12 green, smooth leaves, and causes a similar skin reaction as poison ivy. It typically grows in wet areas.
Most stings are self-limited. Topical corticosteroid creams may be used if needed.
This case and photo were submitted by Susannah McClain, MD, of Three Rivers Dermatology in Coraopolis, Pa., and Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
Urticaria from stinging nettle
The stinging nettle (Urtica dioica) is a plant that grows in the United States, Eurasia, Northern Africa, and some parts of South America. It is commonly found in patches along hiking trails and near streams. The leaves are green with a characteristic tapered tip and bear tiny spines or hairs. The spines contain substances such as histamine, serotonin, and acetylcholine. Within seconds of contact with the stinging nettle, sharp stinging and burning will occur. Urticaria and pruritus may appear a few minutes later and may last up to 24 hours. The plant is eaten in some parts of the world and has been used as medicine.
The wood nettle (Laportea canadensis) is a relative of the stinging nettle that often grows in woodlands. Like the stinging nettle, the wood nettle leaves are covered with spines that sting when they come into contact with skin. However, the leaves are shorter and more oval shaped that the stinging nettle, and they lack the tapered tip that is characteristic for the stinging nettle. The reaction from the wood nettle is generally milder than that of the stinging nettle.
Plants can illicit different types of reactions in the skin: urticaria (immunologic and toxin mediated), irritant dermatitis (mechanical and chemical), phototoxic dermatitis (phytophotodermatitis), and allergic contact dermatitis. where anyone coming into contact with the hairs of the plant can be affected. Previous sensitization is not required. The reaction usually occurs immediately after exposure.
The allergic contact dermatitis seen with toxicodendron (poison ivy and poison sumac) appears 48 hours after exposure of a previously sensitized person to the plant. This type of delayed hypersensitivity reaction is known as cell-mediated hypersensitivity. Generally, no reaction is elicited upon the first exposure to the allergen. In fact, it may take years of exposure to allergens for someone to develop an allergic contact dermatitis.
The poison ivy plant can grow anywhere and is characteristically found in “leaves of three.” Skin reactions are often appear as linearly-arranged vesicles a few days after the exposure to the urushiol chemical in the sap of the plant. Poison sumac has red stems with 7-12 green, smooth leaves, and causes a similar skin reaction as poison ivy. It typically grows in wet areas.
Most stings are self-limited. Topical corticosteroid creams may be used if needed.
This case and photo were submitted by Susannah McClain, MD, of Three Rivers Dermatology in Coraopolis, Pa., and Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
Encourage participation in team sports
Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.
Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.
The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.
Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,1 possibly because of the social connections to peers and adults that grow out of them.
In the Monitoring the Future surveys (biannual national surveys of high school student health and behaviors funded by the National Institutes of Health) from 2010 to 2015, teenagers who participated in team sports were more likely to describe higher self-esteem and lower levels of loneliness. It is important to note that it has been difficult to establish the causal direction of the association between team sports and mental health in youth. We need more prospective randomized controlled trials to assert that the benefit is not simply an artifact of healthier youth choosing to participate in sports, but actually an active consequence of that choice. For now, though, we can say with confidence that physical activity promotes good mental health in youth and may protect against mental illness.
While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.
Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.
Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.2
Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.
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 pdnews@mdedge.com.
References
1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.
2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.
Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.
Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.
The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.
Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,1 possibly because of the social connections to peers and adults that grow out of them.
In the Monitoring the Future surveys (biannual national surveys of high school student health and behaviors funded by the National Institutes of Health) from 2010 to 2015, teenagers who participated in team sports were more likely to describe higher self-esteem and lower levels of loneliness. It is important to note that it has been difficult to establish the causal direction of the association between team sports and mental health in youth. We need more prospective randomized controlled trials to assert that the benefit is not simply an artifact of healthier youth choosing to participate in sports, but actually an active consequence of that choice. For now, though, we can say with confidence that physical activity promotes good mental health in youth and may protect against mental illness.
While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.
Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.
Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.2
Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.
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 pdnews@mdedge.com.
References
1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.
2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.
Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.
Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.
The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.
Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,1 possibly because of the social connections to peers and adults that grow out of them.
In the Monitoring the Future surveys (biannual national surveys of high school student health and behaviors funded by the National Institutes of Health) from 2010 to 2015, teenagers who participated in team sports were more likely to describe higher self-esteem and lower levels of loneliness. It is important to note that it has been difficult to establish the causal direction of the association between team sports and mental health in youth. We need more prospective randomized controlled trials to assert that the benefit is not simply an artifact of healthier youth choosing to participate in sports, but actually an active consequence of that choice. For now, though, we can say with confidence that physical activity promotes good mental health in youth and may protect against mental illness.
While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.
Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.
Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.2
Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.
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 pdnews@mdedge.com.
References
1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.
2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.