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COAPT: MitraClip prolongs life in selected HF patients
SAN DIEGO – Among a carefully selected subset of heart failure patients and severe secondary mitral regurgitation, transcatheter mitral valve repair with the MitraClip reduced hospitalizations for heart failure by 47%, and death from any cause by 38% over 24 months, compared with maximal medical therapy alone.
That’s according to a randomized, open-label trial presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
The number needed to treat to prevent one heart failure (HF) hospitalization within 2 years was three; the number needed to treat to save one life was six. Only about 3% of patients had a device complication within 12 months of placement in the study, dubbed COAPT (the Heart Failure Patients with Functional Mitral Regurgitation Trial).
COAPT patients had grade 3+ or 4+ secondary mitral regurgitation, with a mean effective regurgitant orifice area (EROA) of 41 mm2. Their left ventricles were dilated, but not huge, with a mean left ventricular end-diastolic volume of 101 mL/m2. “We estimate that’s about 10% of heart failure patients,” said lead investigator and interventional cardiologist Gregg W. Stone, MD, a professor of medicine at Columbia University, New York.
MitraClip placement was performed in high-volume centers by experienced operators, and patients were on maximally tolerated doses of guideline-directed medical therapy, as per the 2013 American College of Cardiology/American Heart Association heart failure management guidelines. There was very little variation in treatment regimens during the 2-year trial (J Am Coll Cardiol. 2017;70:776-803).
Those parameters matter. Among HF patients who did not fit them in the recent Mitra-FR trial in France, MitraClip did not reduce rates of death or unplanned hospitalization (N Engl J Med. 2018 Aug 27. doi: 10.1056/NEJMoa1805374).
COAPT and Mitra-FR investigators said at the meeting that the studies are complimentary, not conflicting, because together, they define secondary mitral regurgitation (MR) patients who will and will not benefit from the device.
MR was less severe in Mitra-FR, with a mean EROA of 31 mm2, but left ventricles were more dilated, with a mean left ventricular end-diastolic volume of 135 mL/m2. Patients were on more real-world drug regimens that varied over the course of the trial. Also, the lower implantation rates and higher complication rates in Mitra-FR “suggests perhaps greater experience of the COAPT operators,” said Dr. Stone, who also is the director of cardiovascular research and education at the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center.
In short, “they were a different patient population than were enrolled in COAPT,” he said at the meeting, sponsored by the Cardiovascular Research Foundation, which Dr. Stone also codirects.
There was great excitement at TCT about COAPT because there was a startling benefit for patients who previously had few options. But many speakers worried that the hype surrounding the trial will drown out the critically important message about patient selection and that the clip will be used in HF patients who don’t fit the COAPT profile.
They also said that the emerging picture of benefit in patients with less ventricular dilation but more mitral regurgitation needs to be fleshed out and better quantified.
COAPT randomized 302 patients to MitraClip on a background of guideline-directed therapy and 312 to guideline-directed therapy alone. Participants who had mitral regurgitation caused by left ventricular dysfunction, were not surgical candidates, and remained symptomatic despite optimal treatment.
The annualized rate of all hospitalizations for HF within 24 months was 35.8% per patient-year in the device group, as compared with 67.9% per patient-year in the control group, for a relative reduction of 47% (P less than .001).
Death from any cause within 24 months occurred in 29.1% of the patients in the device group and 46.1% in the control group, yielding a reduction of 38% (P less than .001).
“We didn’t cure patients by fixing their MR. They still had 29% 2-year mortality, but we did markedly improve their quality of life. The only subgroup that didn’t benefit were patients that had an EORA of less than 30 mm2 and end diastolic volume greater than the median” of 96 mL/m2, which was “fascinating,” Dr. Stone said, and fit the emerging picture.
Mitral regurgitation grade fell to 1+ or lower in 82% of patients after clip placement and remained there in the majority of survivors at 2 years.
For a long time, “HF experts thought MR was just a marker of severe left ventricular dysfunction. What I think we see here is that secondary MR is not just a bystander. It contributes to the abnormal pathophysiology of these patients,” he said.
The trial was sponsored by MitraClip’s maker, Abbott. The company participated in site selection, management, and data analysis. Dr. Stone disclosed that his employer, Columbia University, receives royalties from Abbott for sale of the clip. Several fellow investigators disclosed grants, fees, and other financial ties to the company.
Simultaneously with the COAPT presentation, the results were published online (N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640).
Mitra-FR was funded by the French Ministry of Health and Research and Abbott.
This is really a blockbuster trial, because you see a statistically significant reduction in cardiovascular endpoints, which is something we almost never see in device-based trials. I think this is going to change clinical practice, but the question of generalizability is tricky. This was such a well-conducted trial; it may be difficult to generalize this to the practicing public. I was impressed by the MitraClip performance: the reduction in MR [mitral regurgitation], the lack of recurrence, and the small number of complications. Perhaps more than anything else, the difference between Mitra-FR and COAPT was the quality of the operators.
Martin B. Leon, MD , is the director of the Center for Interventional Vascular Therapy at Columbia University, N.Y., and the Cardiovascular Research Foundation’s founder and codirector of medical research and education. He was not involved in COAPT, and made his comments after the study presentation.
This is really a blockbuster trial, because you see a statistically significant reduction in cardiovascular endpoints, which is something we almost never see in device-based trials. I think this is going to change clinical practice, but the question of generalizability is tricky. This was such a well-conducted trial; it may be difficult to generalize this to the practicing public. I was impressed by the MitraClip performance: the reduction in MR [mitral regurgitation], the lack of recurrence, and the small number of complications. Perhaps more than anything else, the difference between Mitra-FR and COAPT was the quality of the operators.
Martin B. Leon, MD , is the director of the Center for Interventional Vascular Therapy at Columbia University, N.Y., and the Cardiovascular Research Foundation’s founder and codirector of medical research and education. He was not involved in COAPT, and made his comments after the study presentation.
This is really a blockbuster trial, because you see a statistically significant reduction in cardiovascular endpoints, which is something we almost never see in device-based trials. I think this is going to change clinical practice, but the question of generalizability is tricky. This was such a well-conducted trial; it may be difficult to generalize this to the practicing public. I was impressed by the MitraClip performance: the reduction in MR [mitral regurgitation], the lack of recurrence, and the small number of complications. Perhaps more than anything else, the difference between Mitra-FR and COAPT was the quality of the operators.
Martin B. Leon, MD , is the director of the Center for Interventional Vascular Therapy at Columbia University, N.Y., and the Cardiovascular Research Foundation’s founder and codirector of medical research and education. He was not involved in COAPT, and made his comments after the study presentation.
SAN DIEGO – Among a carefully selected subset of heart failure patients and severe secondary mitral regurgitation, transcatheter mitral valve repair with the MitraClip reduced hospitalizations for heart failure by 47%, and death from any cause by 38% over 24 months, compared with maximal medical therapy alone.
That’s according to a randomized, open-label trial presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
The number needed to treat to prevent one heart failure (HF) hospitalization within 2 years was three; the number needed to treat to save one life was six. Only about 3% of patients had a device complication within 12 months of placement in the study, dubbed COAPT (the Heart Failure Patients with Functional Mitral Regurgitation Trial).
COAPT patients had grade 3+ or 4+ secondary mitral regurgitation, with a mean effective regurgitant orifice area (EROA) of 41 mm2. Their left ventricles were dilated, but not huge, with a mean left ventricular end-diastolic volume of 101 mL/m2. “We estimate that’s about 10% of heart failure patients,” said lead investigator and interventional cardiologist Gregg W. Stone, MD, a professor of medicine at Columbia University, New York.
MitraClip placement was performed in high-volume centers by experienced operators, and patients were on maximally tolerated doses of guideline-directed medical therapy, as per the 2013 American College of Cardiology/American Heart Association heart failure management guidelines. There was very little variation in treatment regimens during the 2-year trial (J Am Coll Cardiol. 2017;70:776-803).
Those parameters matter. Among HF patients who did not fit them in the recent Mitra-FR trial in France, MitraClip did not reduce rates of death or unplanned hospitalization (N Engl J Med. 2018 Aug 27. doi: 10.1056/NEJMoa1805374).
COAPT and Mitra-FR investigators said at the meeting that the studies are complimentary, not conflicting, because together, they define secondary mitral regurgitation (MR) patients who will and will not benefit from the device.
MR was less severe in Mitra-FR, with a mean EROA of 31 mm2, but left ventricles were more dilated, with a mean left ventricular end-diastolic volume of 135 mL/m2. Patients were on more real-world drug regimens that varied over the course of the trial. Also, the lower implantation rates and higher complication rates in Mitra-FR “suggests perhaps greater experience of the COAPT operators,” said Dr. Stone, who also is the director of cardiovascular research and education at the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center.
In short, “they were a different patient population than were enrolled in COAPT,” he said at the meeting, sponsored by the Cardiovascular Research Foundation, which Dr. Stone also codirects.
There was great excitement at TCT about COAPT because there was a startling benefit for patients who previously had few options. But many speakers worried that the hype surrounding the trial will drown out the critically important message about patient selection and that the clip will be used in HF patients who don’t fit the COAPT profile.
They also said that the emerging picture of benefit in patients with less ventricular dilation but more mitral regurgitation needs to be fleshed out and better quantified.
COAPT randomized 302 patients to MitraClip on a background of guideline-directed therapy and 312 to guideline-directed therapy alone. Participants who had mitral regurgitation caused by left ventricular dysfunction, were not surgical candidates, and remained symptomatic despite optimal treatment.
The annualized rate of all hospitalizations for HF within 24 months was 35.8% per patient-year in the device group, as compared with 67.9% per patient-year in the control group, for a relative reduction of 47% (P less than .001).
Death from any cause within 24 months occurred in 29.1% of the patients in the device group and 46.1% in the control group, yielding a reduction of 38% (P less than .001).
“We didn’t cure patients by fixing their MR. They still had 29% 2-year mortality, but we did markedly improve their quality of life. The only subgroup that didn’t benefit were patients that had an EORA of less than 30 mm2 and end diastolic volume greater than the median” of 96 mL/m2, which was “fascinating,” Dr. Stone said, and fit the emerging picture.
Mitral regurgitation grade fell to 1+ or lower in 82% of patients after clip placement and remained there in the majority of survivors at 2 years.
For a long time, “HF experts thought MR was just a marker of severe left ventricular dysfunction. What I think we see here is that secondary MR is not just a bystander. It contributes to the abnormal pathophysiology of these patients,” he said.
The trial was sponsored by MitraClip’s maker, Abbott. The company participated in site selection, management, and data analysis. Dr. Stone disclosed that his employer, Columbia University, receives royalties from Abbott for sale of the clip. Several fellow investigators disclosed grants, fees, and other financial ties to the company.
Simultaneously with the COAPT presentation, the results were published online (N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640).
Mitra-FR was funded by the French Ministry of Health and Research and Abbott.
SAN DIEGO – Among a carefully selected subset of heart failure patients and severe secondary mitral regurgitation, transcatheter mitral valve repair with the MitraClip reduced hospitalizations for heart failure by 47%, and death from any cause by 38% over 24 months, compared with maximal medical therapy alone.
That’s according to a randomized, open-label trial presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
The number needed to treat to prevent one heart failure (HF) hospitalization within 2 years was three; the number needed to treat to save one life was six. Only about 3% of patients had a device complication within 12 months of placement in the study, dubbed COAPT (the Heart Failure Patients with Functional Mitral Regurgitation Trial).
COAPT patients had grade 3+ or 4+ secondary mitral regurgitation, with a mean effective regurgitant orifice area (EROA) of 41 mm2. Their left ventricles were dilated, but not huge, with a mean left ventricular end-diastolic volume of 101 mL/m2. “We estimate that’s about 10% of heart failure patients,” said lead investigator and interventional cardiologist Gregg W. Stone, MD, a professor of medicine at Columbia University, New York.
MitraClip placement was performed in high-volume centers by experienced operators, and patients were on maximally tolerated doses of guideline-directed medical therapy, as per the 2013 American College of Cardiology/American Heart Association heart failure management guidelines. There was very little variation in treatment regimens during the 2-year trial (J Am Coll Cardiol. 2017;70:776-803).
Those parameters matter. Among HF patients who did not fit them in the recent Mitra-FR trial in France, MitraClip did not reduce rates of death or unplanned hospitalization (N Engl J Med. 2018 Aug 27. doi: 10.1056/NEJMoa1805374).
COAPT and Mitra-FR investigators said at the meeting that the studies are complimentary, not conflicting, because together, they define secondary mitral regurgitation (MR) patients who will and will not benefit from the device.
MR was less severe in Mitra-FR, with a mean EROA of 31 mm2, but left ventricles were more dilated, with a mean left ventricular end-diastolic volume of 135 mL/m2. Patients were on more real-world drug regimens that varied over the course of the trial. Also, the lower implantation rates and higher complication rates in Mitra-FR “suggests perhaps greater experience of the COAPT operators,” said Dr. Stone, who also is the director of cardiovascular research and education at the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center.
In short, “they were a different patient population than were enrolled in COAPT,” he said at the meeting, sponsored by the Cardiovascular Research Foundation, which Dr. Stone also codirects.
There was great excitement at TCT about COAPT because there was a startling benefit for patients who previously had few options. But many speakers worried that the hype surrounding the trial will drown out the critically important message about patient selection and that the clip will be used in HF patients who don’t fit the COAPT profile.
They also said that the emerging picture of benefit in patients with less ventricular dilation but more mitral regurgitation needs to be fleshed out and better quantified.
COAPT randomized 302 patients to MitraClip on a background of guideline-directed therapy and 312 to guideline-directed therapy alone. Participants who had mitral regurgitation caused by left ventricular dysfunction, were not surgical candidates, and remained symptomatic despite optimal treatment.
The annualized rate of all hospitalizations for HF within 24 months was 35.8% per patient-year in the device group, as compared with 67.9% per patient-year in the control group, for a relative reduction of 47% (P less than .001).
Death from any cause within 24 months occurred in 29.1% of the patients in the device group and 46.1% in the control group, yielding a reduction of 38% (P less than .001).
“We didn’t cure patients by fixing their MR. They still had 29% 2-year mortality, but we did markedly improve their quality of life. The only subgroup that didn’t benefit were patients that had an EORA of less than 30 mm2 and end diastolic volume greater than the median” of 96 mL/m2, which was “fascinating,” Dr. Stone said, and fit the emerging picture.
Mitral regurgitation grade fell to 1+ or lower in 82% of patients after clip placement and remained there in the majority of survivors at 2 years.
For a long time, “HF experts thought MR was just a marker of severe left ventricular dysfunction. What I think we see here is that secondary MR is not just a bystander. It contributes to the abnormal pathophysiology of these patients,” he said.
The trial was sponsored by MitraClip’s maker, Abbott. The company participated in site selection, management, and data analysis. Dr. Stone disclosed that his employer, Columbia University, receives royalties from Abbott for sale of the clip. Several fellow investigators disclosed grants, fees, and other financial ties to the company.
Simultaneously with the COAPT presentation, the results were published online (N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640).
Mitra-FR was funded by the French Ministry of Health and Research and Abbott.
REPORTING FROM TCT 2018
Key clinical point: MitraClip reduced death and heart failure hospitalizations in certain patients, but
Major finding: Among a subset of heart failure patients with moderately dilated left ventricles and severe secondary mitral regurgitation, transcatheter mitral valve repair with the MitraClip reduced hospitalizations for heart failure within 24 months by 47%, and death from any cause within 24 months by 38%, compared with maximal medical therapy alone.
Study details: COAPT, a randomized, open-label trial with 614 subjects
Disclosures: The work was funded by MitraClip maker, Abbott. The company participated in site selection, management, and data analysis. The lead and several other investigators disclosed financial ties to the company.
FDA grants OBI-3424 orphan designation for ALL
The Food and Drug Administration has granted orphan drug designation to OBI-3424 for the treatment of acute lymphoblastic leukemia (ALL).
OBI-3424 is a small-molecule prodrug that targets cancers overexpressing aldo-keto reductase 1C3 (AKR1C3) and selectively releases a DNA alkylating agent in the presence of the AKR1C3 enzyme.
AKR1C3 overexpression has been observed in ALL, particularly T-cell ALL.
OBI-3424 demonstrated activity against T-ALL in preclinical research presented as a poster at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2017.
Researchers reported that OBI-3424 “exerted profound in vivo efficacy” against T-ALL xenografts derived mainly from patients with aggressive and fatal T-ALL. In addition, OBI-3424 significantly reduced leukemia bone marrow infiltration in four of six evaluable T-ALL xenografts, and OBI-3424 was considered well tolerated.
The poster presentation describing this research is available for download from the website of OBI Pharma, the company developing OBI-3424 in cooperation with Ascenta Pharma.
OBI-3424 also has orphan drug designation from the FDA as a treatment for hepatocellular carcinoma.
The Food and Drug Administration has granted orphan drug designation to OBI-3424 for the treatment of acute lymphoblastic leukemia (ALL).
OBI-3424 is a small-molecule prodrug that targets cancers overexpressing aldo-keto reductase 1C3 (AKR1C3) and selectively releases a DNA alkylating agent in the presence of the AKR1C3 enzyme.
AKR1C3 overexpression has been observed in ALL, particularly T-cell ALL.
OBI-3424 demonstrated activity against T-ALL in preclinical research presented as a poster at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2017.
Researchers reported that OBI-3424 “exerted profound in vivo efficacy” against T-ALL xenografts derived mainly from patients with aggressive and fatal T-ALL. In addition, OBI-3424 significantly reduced leukemia bone marrow infiltration in four of six evaluable T-ALL xenografts, and OBI-3424 was considered well tolerated.
The poster presentation describing this research is available for download from the website of OBI Pharma, the company developing OBI-3424 in cooperation with Ascenta Pharma.
OBI-3424 also has orphan drug designation from the FDA as a treatment for hepatocellular carcinoma.
The Food and Drug Administration has granted orphan drug designation to OBI-3424 for the treatment of acute lymphoblastic leukemia (ALL).
OBI-3424 is a small-molecule prodrug that targets cancers overexpressing aldo-keto reductase 1C3 (AKR1C3) and selectively releases a DNA alkylating agent in the presence of the AKR1C3 enzyme.
AKR1C3 overexpression has been observed in ALL, particularly T-cell ALL.
OBI-3424 demonstrated activity against T-ALL in preclinical research presented as a poster at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2017.
Researchers reported that OBI-3424 “exerted profound in vivo efficacy” against T-ALL xenografts derived mainly from patients with aggressive and fatal T-ALL. In addition, OBI-3424 significantly reduced leukemia bone marrow infiltration in four of six evaluable T-ALL xenografts, and OBI-3424 was considered well tolerated.
The poster presentation describing this research is available for download from the website of OBI Pharma, the company developing OBI-3424 in cooperation with Ascenta Pharma.
OBI-3424 also has orphan drug designation from the FDA as a treatment for hepatocellular carcinoma.
ADHD in the long term
Parents whose kids are diagnosed with ADHD face important questions about what to expect in the long term and how that might inform treatment. Studies find that ADHD diagnosed in childhood tends to persist in up to 65% of adolescents (some estimates are lower depending on criteria used),1 and about 50% of people are estimated to continue to meet criteria for ADHD as adults.2 Many studies have attempted to understand what long-term risks are associated with ADHD, as well as the factors that help better predict which characteristics in childhood might predict those risks. A recent article was published on a cohort of boys followed over 33 years.3 This, as well as other large prospective studies, such as the Multimodal Treatment of ADHD (MTA) provide us with helpful long-range data that inform this article.4-6 This article reviews risks in adolescence and adulthood and the factors thought to be associated with them.
What predicts persistence of ADHD symptoms in adolescence?
Several factors emerge consistently, including higher symptom severity, comorbid conduct disorder, and lower childhood IQ; other findings include family-related factors, such as lower parental mental health, less-positive parenting, and lower rates of parental education. In general, hyperactivity and impulsivity wanes, while inattention symptoms remain more stable.
What does ADHD predict for adolescents?
Adolescents with ADHD are more than twice as likely to be involved in pregnancies under the age of 18 years, true for both male and female genders.7 This finding also is associated with increased substance use and low academic achievement but not completely explained by it. Adolescents with persistent ADHD symptoms experience poorer educational success than do kids without ADHD symptoms, according to teacher reports of performance and measurements of grade point average. They are more likely to repeat a grade.8 Related but independent is the relationship of substance use disorders in kids with ADHD. Adolescents with ADHD are more likely to use nicotine or marijuana or meet criteria for any substance use disorder than adolescents without ADHD. Finally, adolescents aged 12-18 years with ADHD are at higher risk for motor vehicle accidents and all types of accidental injuries.9
What predicts persistence of ADHD symptoms in adulthood?
A follow-up study of the MTA trial 16 years later looked at ADHD diagnosed before age 12 years and the association with symptom persistence in adulthood, defined by the DSM-5 cutoff criteria of five symptoms. The following factors related to symptom persistence: childhood psychiatric comorbidity, higher ADHD symptom severity, and parental mental health problems. Notably, family socioeconomic status, child IQ, and parental education were not associated. In addition to looking at symptom persistence, other studies have looked at predictors of functional impairment in adulthood following a childhood ADHD diagnosis (independent of whether people continue to meet criteria for the disorder). The main findings that seem consistently related to all functional outcomes, including social, occupational, and educational, are lower childhood IQ and history of conduct problems (in the absence of meeting criteria for full childhood conduct disorder). Educational family-related factors, such as socioeconomic status and lower parental education, were related to lower educational functioning only.
What does ADHD predict for adults?
It appears that overall, adults who were diagnosed with ADHD as children show poorer functional outcomes than did those who weren’t, and there is a step-wise relationship when considering adults whose symptoms persist, with more severe outcomes compared with adults whose symptoms have desisted, who in turn have worse outcomes than adults who were never diagnosed with ADHD. Educational attainments follow this pattern with the highest average levels of education in the non-ADHD group and the lowest average years in the group with persistent symptoms. Occupational success and percent receiving public assistance again separated between each group, with the symptom persisters faring the worst, the symptom desisters better, and those never affected by ADHD, the best. In terms of emotional disorders, it was only the symptom persisters who suffered from higher rates of mood and anxiety disorders. Similarly, only the symptom persisters had significantly more marijuana use disorders. No other substance use disorders or legal outcomes were significant.
How does this affect how we approach treatment?
Clinicians and researchers who specialize in ADHD have been arguing for ADHD to be treated as more of a chronic disease and for impairment to be the focus of treatment, rather than simply symptom control.10 With what we know about long-term functional impairment, there is reason to consider a more holistic picture of a child or an adolescent and how they are functioning in their academic, emotional, and social domains. A meta-analysis of treatment and long-term outcomes suggests that psychostimulant treatment, psychotherapy treatment, and combined treatment all improve long-term functioning, especially self-esteem, social functioning, and academic functioning, with combined psychotherapeutic and pharmacologic treatments associated with the highest effect sizes.11
For those who treat ADHD, it is our job to provide education to families about the chronic risks associated with the diagnosis, and the importance of offering multimodal therapy that can address family factors that might be contributing to risks, as well as the child’s overall well-being. If we are to make sense of how adults may experience impairment even in the absence of ongoing symptoms, we might look at how their overall wellness was interrupted during development. Maybe they fell into a different crowd of kids? Maybe they stopped achieving at school in a way that changed the achievement trajectory they were on? Maybe they impulsively picked up substances or got in trouble with the law? These events can have lasting impacts on well-being. We must use medicine and psychotherapy to help with symptoms, but we must look beyond treating illness and use evidence-based strategies to promote wellness at the level of the entire family.
Dr. Guth is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and the University of Vermont, both in Burlington. She works with children and adolescents as well as women in the perinatal period. She has no relevant financial disclosures.
References
1. Psychol Med. 2006 Feb;36(2):159-65.
2. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):937-44.e4.
3. J Am Acad Child Adolesc Psychiatry. 2018 Aug;57(8):571-82.e1.
4. J Am Acad Child Adolesc Psychiatry. 2017 Aug;56(8):687-95.e7.
5. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):945-52.e2.
6. J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):484-500.
7. J Atten Disord. 2017 Sep 1:1087054717730610. doi: 10.1177/1087054717730610.
8. J Atten Disord. 2016 May;20(5):383-9.
9. Eur Child Adolesc Psychiatry. 2014 Feb;23(2):95-102.
10. JAMA Pediatr. 2018 Aug 13. doi: 10.1001/jamapediatrics.2018.1642.
11. PLoS One. 2015 Feb 25;10(2):e0116407.
Parents whose kids are diagnosed with ADHD face important questions about what to expect in the long term and how that might inform treatment. Studies find that ADHD diagnosed in childhood tends to persist in up to 65% of adolescents (some estimates are lower depending on criteria used),1 and about 50% of people are estimated to continue to meet criteria for ADHD as adults.2 Many studies have attempted to understand what long-term risks are associated with ADHD, as well as the factors that help better predict which characteristics in childhood might predict those risks. A recent article was published on a cohort of boys followed over 33 years.3 This, as well as other large prospective studies, such as the Multimodal Treatment of ADHD (MTA) provide us with helpful long-range data that inform this article.4-6 This article reviews risks in adolescence and adulthood and the factors thought to be associated with them.
What predicts persistence of ADHD symptoms in adolescence?
Several factors emerge consistently, including higher symptom severity, comorbid conduct disorder, and lower childhood IQ; other findings include family-related factors, such as lower parental mental health, less-positive parenting, and lower rates of parental education. In general, hyperactivity and impulsivity wanes, while inattention symptoms remain more stable.
What does ADHD predict for adolescents?
Adolescents with ADHD are more than twice as likely to be involved in pregnancies under the age of 18 years, true for both male and female genders.7 This finding also is associated with increased substance use and low academic achievement but not completely explained by it. Adolescents with persistent ADHD symptoms experience poorer educational success than do kids without ADHD symptoms, according to teacher reports of performance and measurements of grade point average. They are more likely to repeat a grade.8 Related but independent is the relationship of substance use disorders in kids with ADHD. Adolescents with ADHD are more likely to use nicotine or marijuana or meet criteria for any substance use disorder than adolescents without ADHD. Finally, adolescents aged 12-18 years with ADHD are at higher risk for motor vehicle accidents and all types of accidental injuries.9
What predicts persistence of ADHD symptoms in adulthood?
A follow-up study of the MTA trial 16 years later looked at ADHD diagnosed before age 12 years and the association with symptom persistence in adulthood, defined by the DSM-5 cutoff criteria of five symptoms. The following factors related to symptom persistence: childhood psychiatric comorbidity, higher ADHD symptom severity, and parental mental health problems. Notably, family socioeconomic status, child IQ, and parental education were not associated. In addition to looking at symptom persistence, other studies have looked at predictors of functional impairment in adulthood following a childhood ADHD diagnosis (independent of whether people continue to meet criteria for the disorder). The main findings that seem consistently related to all functional outcomes, including social, occupational, and educational, are lower childhood IQ and history of conduct problems (in the absence of meeting criteria for full childhood conduct disorder). Educational family-related factors, such as socioeconomic status and lower parental education, were related to lower educational functioning only.
What does ADHD predict for adults?
It appears that overall, adults who were diagnosed with ADHD as children show poorer functional outcomes than did those who weren’t, and there is a step-wise relationship when considering adults whose symptoms persist, with more severe outcomes compared with adults whose symptoms have desisted, who in turn have worse outcomes than adults who were never diagnosed with ADHD. Educational attainments follow this pattern with the highest average levels of education in the non-ADHD group and the lowest average years in the group with persistent symptoms. Occupational success and percent receiving public assistance again separated between each group, with the symptom persisters faring the worst, the symptom desisters better, and those never affected by ADHD, the best. In terms of emotional disorders, it was only the symptom persisters who suffered from higher rates of mood and anxiety disorders. Similarly, only the symptom persisters had significantly more marijuana use disorders. No other substance use disorders or legal outcomes were significant.
How does this affect how we approach treatment?
Clinicians and researchers who specialize in ADHD have been arguing for ADHD to be treated as more of a chronic disease and for impairment to be the focus of treatment, rather than simply symptom control.10 With what we know about long-term functional impairment, there is reason to consider a more holistic picture of a child or an adolescent and how they are functioning in their academic, emotional, and social domains. A meta-analysis of treatment and long-term outcomes suggests that psychostimulant treatment, psychotherapy treatment, and combined treatment all improve long-term functioning, especially self-esteem, social functioning, and academic functioning, with combined psychotherapeutic and pharmacologic treatments associated with the highest effect sizes.11
For those who treat ADHD, it is our job to provide education to families about the chronic risks associated with the diagnosis, and the importance of offering multimodal therapy that can address family factors that might be contributing to risks, as well as the child’s overall well-being. If we are to make sense of how adults may experience impairment even in the absence of ongoing symptoms, we might look at how their overall wellness was interrupted during development. Maybe they fell into a different crowd of kids? Maybe they stopped achieving at school in a way that changed the achievement trajectory they were on? Maybe they impulsively picked up substances or got in trouble with the law? These events can have lasting impacts on well-being. We must use medicine and psychotherapy to help with symptoms, but we must look beyond treating illness and use evidence-based strategies to promote wellness at the level of the entire family.
Dr. Guth is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and the University of Vermont, both in Burlington. She works with children and adolescents as well as women in the perinatal period. She has no relevant financial disclosures.
References
1. Psychol Med. 2006 Feb;36(2):159-65.
2. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):937-44.e4.
3. J Am Acad Child Adolesc Psychiatry. 2018 Aug;57(8):571-82.e1.
4. J Am Acad Child Adolesc Psychiatry. 2017 Aug;56(8):687-95.e7.
5. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):945-52.e2.
6. J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):484-500.
7. J Atten Disord. 2017 Sep 1:1087054717730610. doi: 10.1177/1087054717730610.
8. J Atten Disord. 2016 May;20(5):383-9.
9. Eur Child Adolesc Psychiatry. 2014 Feb;23(2):95-102.
10. JAMA Pediatr. 2018 Aug 13. doi: 10.1001/jamapediatrics.2018.1642.
11. PLoS One. 2015 Feb 25;10(2):e0116407.
Parents whose kids are diagnosed with ADHD face important questions about what to expect in the long term and how that might inform treatment. Studies find that ADHD diagnosed in childhood tends to persist in up to 65% of adolescents (some estimates are lower depending on criteria used),1 and about 50% of people are estimated to continue to meet criteria for ADHD as adults.2 Many studies have attempted to understand what long-term risks are associated with ADHD, as well as the factors that help better predict which characteristics in childhood might predict those risks. A recent article was published on a cohort of boys followed over 33 years.3 This, as well as other large prospective studies, such as the Multimodal Treatment of ADHD (MTA) provide us with helpful long-range data that inform this article.4-6 This article reviews risks in adolescence and adulthood and the factors thought to be associated with them.
What predicts persistence of ADHD symptoms in adolescence?
Several factors emerge consistently, including higher symptom severity, comorbid conduct disorder, and lower childhood IQ; other findings include family-related factors, such as lower parental mental health, less-positive parenting, and lower rates of parental education. In general, hyperactivity and impulsivity wanes, while inattention symptoms remain more stable.
What does ADHD predict for adolescents?
Adolescents with ADHD are more than twice as likely to be involved in pregnancies under the age of 18 years, true for both male and female genders.7 This finding also is associated with increased substance use and low academic achievement but not completely explained by it. Adolescents with persistent ADHD symptoms experience poorer educational success than do kids without ADHD symptoms, according to teacher reports of performance and measurements of grade point average. They are more likely to repeat a grade.8 Related but independent is the relationship of substance use disorders in kids with ADHD. Adolescents with ADHD are more likely to use nicotine or marijuana or meet criteria for any substance use disorder than adolescents without ADHD. Finally, adolescents aged 12-18 years with ADHD are at higher risk for motor vehicle accidents and all types of accidental injuries.9
What predicts persistence of ADHD symptoms in adulthood?
A follow-up study of the MTA trial 16 years later looked at ADHD diagnosed before age 12 years and the association with symptom persistence in adulthood, defined by the DSM-5 cutoff criteria of five symptoms. The following factors related to symptom persistence: childhood psychiatric comorbidity, higher ADHD symptom severity, and parental mental health problems. Notably, family socioeconomic status, child IQ, and parental education were not associated. In addition to looking at symptom persistence, other studies have looked at predictors of functional impairment in adulthood following a childhood ADHD diagnosis (independent of whether people continue to meet criteria for the disorder). The main findings that seem consistently related to all functional outcomes, including social, occupational, and educational, are lower childhood IQ and history of conduct problems (in the absence of meeting criteria for full childhood conduct disorder). Educational family-related factors, such as socioeconomic status and lower parental education, were related to lower educational functioning only.
What does ADHD predict for adults?
It appears that overall, adults who were diagnosed with ADHD as children show poorer functional outcomes than did those who weren’t, and there is a step-wise relationship when considering adults whose symptoms persist, with more severe outcomes compared with adults whose symptoms have desisted, who in turn have worse outcomes than adults who were never diagnosed with ADHD. Educational attainments follow this pattern with the highest average levels of education in the non-ADHD group and the lowest average years in the group with persistent symptoms. Occupational success and percent receiving public assistance again separated between each group, with the symptom persisters faring the worst, the symptom desisters better, and those never affected by ADHD, the best. In terms of emotional disorders, it was only the symptom persisters who suffered from higher rates of mood and anxiety disorders. Similarly, only the symptom persisters had significantly more marijuana use disorders. No other substance use disorders or legal outcomes were significant.
How does this affect how we approach treatment?
Clinicians and researchers who specialize in ADHD have been arguing for ADHD to be treated as more of a chronic disease and for impairment to be the focus of treatment, rather than simply symptom control.10 With what we know about long-term functional impairment, there is reason to consider a more holistic picture of a child or an adolescent and how they are functioning in their academic, emotional, and social domains. A meta-analysis of treatment and long-term outcomes suggests that psychostimulant treatment, psychotherapy treatment, and combined treatment all improve long-term functioning, especially self-esteem, social functioning, and academic functioning, with combined psychotherapeutic and pharmacologic treatments associated with the highest effect sizes.11
For those who treat ADHD, it is our job to provide education to families about the chronic risks associated with the diagnosis, and the importance of offering multimodal therapy that can address family factors that might be contributing to risks, as well as the child’s overall well-being. If we are to make sense of how adults may experience impairment even in the absence of ongoing symptoms, we might look at how their overall wellness was interrupted during development. Maybe they fell into a different crowd of kids? Maybe they stopped achieving at school in a way that changed the achievement trajectory they were on? Maybe they impulsively picked up substances or got in trouble with the law? These events can have lasting impacts on well-being. We must use medicine and psychotherapy to help with symptoms, but we must look beyond treating illness and use evidence-based strategies to promote wellness at the level of the entire family.
Dr. Guth is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and the University of Vermont, both in Burlington. She works with children and adolescents as well as women in the perinatal period. She has no relevant financial disclosures.
References
1. Psychol Med. 2006 Feb;36(2):159-65.
2. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):937-44.e4.
3. J Am Acad Child Adolesc Psychiatry. 2018 Aug;57(8):571-82.e1.
4. J Am Acad Child Adolesc Psychiatry. 2017 Aug;56(8):687-95.e7.
5. J Am Acad Child Adolesc Psychiatry. 2016 Nov;55(11):945-52.e2.
6. J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):484-500.
7. J Atten Disord. 2017 Sep 1:1087054717730610. doi: 10.1177/1087054717730610.
8. J Atten Disord. 2016 May;20(5):383-9.
9. Eur Child Adolesc Psychiatry. 2014 Feb;23(2):95-102.
10. JAMA Pediatr. 2018 Aug 13. doi: 10.1001/jamapediatrics.2018.1642.
11. PLoS One. 2015 Feb 25;10(2):e0116407.
Pregnancy registries are a valuable resource for dermatologists
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Expert shares laser hair removal clinical pearls
SAN DIEGO – annually than for other applications, Kristen M. Kelly, MD, said at the annual Masters of Aesthetics Symposium.
Clinicians perform an estimated 445,000 laser hair removal procedures each year, trailing those performed for wrinkles (561,000), facial redness (598,000), and sun damage (610,000), according to the 2017 American Society for Dermatologic Surgery Procedures Survey. However, hair removal has been found to be the most common procedure resulting in litigation (JAMA Dermatol. 2013;149[2]:188-93), “which is what we want to avoid,” Dr. Kelly said. “We want to learn how to do it in the best way possible.”
Dr. Kelly, professor of dermatology and surgery at the University of California, Irvine, pointed out that clinicians are targeting melanin during laser hair removal. “This is important because it means that gray, white, blonde, and in some cases, red hair are not going to respond very well. In order to reach stem cells in the hair follicle, you can’t use superficial wavelengths, so we end up using the 755-nm alexandrite laser, 810-nm diode laser, or the 1064-nm long-pulsed Nd:YAG laser for the most part in order to get our result. You can also use intense pulsed light at 590-1200 nm.”
The pulse duration should be on the order of the thermal relaxation time (TRT) of the target. She defined thermal relaxation time as the duration required for the heat generated by absorbed light energy within the chromophore to dissipate to 50% of its value immediately after laser exposure.
“We want that heat to be absorbed by the melanin in the hair,” Dr. Kelly said. “Then we want that heat to radiate out to the hair follicle and the stem cells, which is going to prevent the hair from coming back in the future.” Epidermal cooling via cryogen spray cooling, contact cooling, or air-cooling allows clinicians to use higher fluences, allows for the use of safe treatment of darker skin types, and decreases treatment discomfort.
Prior to performing laser hair removal on the perioral area, Dr. Kelly provides a prophylactic antiviral medication for patients with a history of herpetic infection to suppress recurrence. She also advises patients to remove sunless tanner or other products from the skin surface, and she shaves or clips hair close to the surface gently, avoiding abrasion or surface damage. Most of the time she does not use a topical anesthetic. “You always want to make sure the laser is functioning properly by checking the laser’s cooling components, etc.,” she said. “I always tell patients, ‘8-10 treatments is not uncommon. You’re going to have fewer hairs and thinner hairs, but it doesn’t mean that you’re going to have zero hairs in this area for the rest of your life.’ Set the expectation correctly.”
Patients should wear protective goggles if being treated in areas other than the face. “If being treated on the face, make sure they’re wearing appropriate protective eyewear such as laser safe eye shields. Those performing the treatment should wear surgical masks and use a smoke evacuator, as there are multiple known carcinogens and environmental toxins in the plume generated by laser hair removal,” she said (JAMA Dermatol. 2016;152[12]:1320-6).
Factors to consider in choosing treatment settings include hair color, the patient’s skin color, hair thickness, hair density, and body location. For example, the genital area may be more pigmented in some patients, and also may be more sensitive. “If you have thicker and darker hair it’s going to absorb more energy, so you have to adjust your settings,” Dr. Kelly said. She also avoids treating acutely tanned patients. “What you don’t want is for a tanned patient have a complication. I’d rather have them wait 2 or 3 weeks and come back. Sometimes it frustrates them a little, but it is safer.”
At the start of each procedure, Dr. Kelly delivers a couple of pulses then asks patients how uncomfortable they are on a scale from 1 to 10. “It often will vary,” she said. “Even if I’ve seen a patient for 10 treatments, some days it will hurt a little more than others. If the patient says it hurts a lot more than it normally does, you need to stop and think. That tells you that something is not right. They might be too tanned, or perhaps the [device] settings are wrong or the laser’s not functioning properly. Monitor the skin response. It takes time to see the final skin response, so wait before adjusting the energy. You want to see mild redness or mild follicular response. People report a little bit of a burning sensation.”
Postprocedure, she routinely applies a topical steroid such as betamethasone or clobetasol immediately after treatment. “That calms down the inflammatory response. If I see an area that I think is going to blister, I will apply the steroid multiple times until I see that response go away.” She asks patients about their pain level and typically applies ice to the treated area for 10 minutes before they leave the office, and they head home with after-care instructions, including a phone number where Dr. Kelly can be reached if patients have concerns. “I call my patients in the evening to ask how they’re doing, and if they have any questions.”
Dr. Kelly does not do laser hair removal inside the eye orbit or between the eyebrows, “because even with eye shields, you can have a problem,” she said. A potential outcome to be aware of is paradoxical hypertrichosis, or increased hair growth after laser hair removal estimated to occur in 0.6%-10% of patients. She discusses this with patients when consenting them. “Some people say this occurs in darker skin types, while others say it happens in people with thicker hair or thinner hair. Some of it occurs on the edges of the treatment area.” The treatment for paradoxical hypertrichosis is to continue laser hair removal and “try to push the energy just a little bit, but be cautious. It can be a difficult problem to resolve.”
Dr. Kelly has noticed a recent uptick at her practice in gender transition patients seeking hair removal procedures. “Removing facial and chest hair may be desirable, and may be covered by the patient’s health insurance,” she said. “Multiple treatments are required. A thick beard area needs to be approached cautiously.”
She referred to future advances in laser hair removal that may involve the use of topical agents to improve outcomes. For example, Sienna Biopharmaceuticals has developed Topical Photoparticle Therapy which, according to its website, uses “silver particles to absorb laser light and convert the light energy into heat to facilitate local tissue injury ... in the case of unwanted light or mixed pigment hair, which can’t be removed with lasers alone, [this process] targets the hair follicle.”
Dr. Kelly disclosed that she is an advisory consultant to Syneron Candela and Allergan. In addition, Allergan has provided drug products to Dr. Kelly for research purposes, while Solta Medical and ThermiRF have provided her with donated light sources for research or clinical use. Dr. Kelly has also received funding from the Sturge-Weber Foundation, the American Society for Laser Medicine and Surgery, and the National Institutes of Health.
[email protected]
SAN DIEGO – annually than for other applications, Kristen M. Kelly, MD, said at the annual Masters of Aesthetics Symposium.
Clinicians perform an estimated 445,000 laser hair removal procedures each year, trailing those performed for wrinkles (561,000), facial redness (598,000), and sun damage (610,000), according to the 2017 American Society for Dermatologic Surgery Procedures Survey. However, hair removal has been found to be the most common procedure resulting in litigation (JAMA Dermatol. 2013;149[2]:188-93), “which is what we want to avoid,” Dr. Kelly said. “We want to learn how to do it in the best way possible.”
Dr. Kelly, professor of dermatology and surgery at the University of California, Irvine, pointed out that clinicians are targeting melanin during laser hair removal. “This is important because it means that gray, white, blonde, and in some cases, red hair are not going to respond very well. In order to reach stem cells in the hair follicle, you can’t use superficial wavelengths, so we end up using the 755-nm alexandrite laser, 810-nm diode laser, or the 1064-nm long-pulsed Nd:YAG laser for the most part in order to get our result. You can also use intense pulsed light at 590-1200 nm.”
The pulse duration should be on the order of the thermal relaxation time (TRT) of the target. She defined thermal relaxation time as the duration required for the heat generated by absorbed light energy within the chromophore to dissipate to 50% of its value immediately after laser exposure.
“We want that heat to be absorbed by the melanin in the hair,” Dr. Kelly said. “Then we want that heat to radiate out to the hair follicle and the stem cells, which is going to prevent the hair from coming back in the future.” Epidermal cooling via cryogen spray cooling, contact cooling, or air-cooling allows clinicians to use higher fluences, allows for the use of safe treatment of darker skin types, and decreases treatment discomfort.
Prior to performing laser hair removal on the perioral area, Dr. Kelly provides a prophylactic antiviral medication for patients with a history of herpetic infection to suppress recurrence. She also advises patients to remove sunless tanner or other products from the skin surface, and she shaves or clips hair close to the surface gently, avoiding abrasion or surface damage. Most of the time she does not use a topical anesthetic. “You always want to make sure the laser is functioning properly by checking the laser’s cooling components, etc.,” she said. “I always tell patients, ‘8-10 treatments is not uncommon. You’re going to have fewer hairs and thinner hairs, but it doesn’t mean that you’re going to have zero hairs in this area for the rest of your life.’ Set the expectation correctly.”
Patients should wear protective goggles if being treated in areas other than the face. “If being treated on the face, make sure they’re wearing appropriate protective eyewear such as laser safe eye shields. Those performing the treatment should wear surgical masks and use a smoke evacuator, as there are multiple known carcinogens and environmental toxins in the plume generated by laser hair removal,” she said (JAMA Dermatol. 2016;152[12]:1320-6).
Factors to consider in choosing treatment settings include hair color, the patient’s skin color, hair thickness, hair density, and body location. For example, the genital area may be more pigmented in some patients, and also may be more sensitive. “If you have thicker and darker hair it’s going to absorb more energy, so you have to adjust your settings,” Dr. Kelly said. She also avoids treating acutely tanned patients. “What you don’t want is for a tanned patient have a complication. I’d rather have them wait 2 or 3 weeks and come back. Sometimes it frustrates them a little, but it is safer.”
At the start of each procedure, Dr. Kelly delivers a couple of pulses then asks patients how uncomfortable they are on a scale from 1 to 10. “It often will vary,” she said. “Even if I’ve seen a patient for 10 treatments, some days it will hurt a little more than others. If the patient says it hurts a lot more than it normally does, you need to stop and think. That tells you that something is not right. They might be too tanned, or perhaps the [device] settings are wrong or the laser’s not functioning properly. Monitor the skin response. It takes time to see the final skin response, so wait before adjusting the energy. You want to see mild redness or mild follicular response. People report a little bit of a burning sensation.”
Postprocedure, she routinely applies a topical steroid such as betamethasone or clobetasol immediately after treatment. “That calms down the inflammatory response. If I see an area that I think is going to blister, I will apply the steroid multiple times until I see that response go away.” She asks patients about their pain level and typically applies ice to the treated area for 10 minutes before they leave the office, and they head home with after-care instructions, including a phone number where Dr. Kelly can be reached if patients have concerns. “I call my patients in the evening to ask how they’re doing, and if they have any questions.”
Dr. Kelly does not do laser hair removal inside the eye orbit or between the eyebrows, “because even with eye shields, you can have a problem,” she said. A potential outcome to be aware of is paradoxical hypertrichosis, or increased hair growth after laser hair removal estimated to occur in 0.6%-10% of patients. She discusses this with patients when consenting them. “Some people say this occurs in darker skin types, while others say it happens in people with thicker hair or thinner hair. Some of it occurs on the edges of the treatment area.” The treatment for paradoxical hypertrichosis is to continue laser hair removal and “try to push the energy just a little bit, but be cautious. It can be a difficult problem to resolve.”
Dr. Kelly has noticed a recent uptick at her practice in gender transition patients seeking hair removal procedures. “Removing facial and chest hair may be desirable, and may be covered by the patient’s health insurance,” she said. “Multiple treatments are required. A thick beard area needs to be approached cautiously.”
She referred to future advances in laser hair removal that may involve the use of topical agents to improve outcomes. For example, Sienna Biopharmaceuticals has developed Topical Photoparticle Therapy which, according to its website, uses “silver particles to absorb laser light and convert the light energy into heat to facilitate local tissue injury ... in the case of unwanted light or mixed pigment hair, which can’t be removed with lasers alone, [this process] targets the hair follicle.”
Dr. Kelly disclosed that she is an advisory consultant to Syneron Candela and Allergan. In addition, Allergan has provided drug products to Dr. Kelly for research purposes, while Solta Medical and ThermiRF have provided her with donated light sources for research or clinical use. Dr. Kelly has also received funding from the Sturge-Weber Foundation, the American Society for Laser Medicine and Surgery, and the National Institutes of Health.
[email protected]
SAN DIEGO – annually than for other applications, Kristen M. Kelly, MD, said at the annual Masters of Aesthetics Symposium.
Clinicians perform an estimated 445,000 laser hair removal procedures each year, trailing those performed for wrinkles (561,000), facial redness (598,000), and sun damage (610,000), according to the 2017 American Society for Dermatologic Surgery Procedures Survey. However, hair removal has been found to be the most common procedure resulting in litigation (JAMA Dermatol. 2013;149[2]:188-93), “which is what we want to avoid,” Dr. Kelly said. “We want to learn how to do it in the best way possible.”
Dr. Kelly, professor of dermatology and surgery at the University of California, Irvine, pointed out that clinicians are targeting melanin during laser hair removal. “This is important because it means that gray, white, blonde, and in some cases, red hair are not going to respond very well. In order to reach stem cells in the hair follicle, you can’t use superficial wavelengths, so we end up using the 755-nm alexandrite laser, 810-nm diode laser, or the 1064-nm long-pulsed Nd:YAG laser for the most part in order to get our result. You can also use intense pulsed light at 590-1200 nm.”
The pulse duration should be on the order of the thermal relaxation time (TRT) of the target. She defined thermal relaxation time as the duration required for the heat generated by absorbed light energy within the chromophore to dissipate to 50% of its value immediately after laser exposure.
“We want that heat to be absorbed by the melanin in the hair,” Dr. Kelly said. “Then we want that heat to radiate out to the hair follicle and the stem cells, which is going to prevent the hair from coming back in the future.” Epidermal cooling via cryogen spray cooling, contact cooling, or air-cooling allows clinicians to use higher fluences, allows for the use of safe treatment of darker skin types, and decreases treatment discomfort.
Prior to performing laser hair removal on the perioral area, Dr. Kelly provides a prophylactic antiviral medication for patients with a history of herpetic infection to suppress recurrence. She also advises patients to remove sunless tanner or other products from the skin surface, and she shaves or clips hair close to the surface gently, avoiding abrasion or surface damage. Most of the time she does not use a topical anesthetic. “You always want to make sure the laser is functioning properly by checking the laser’s cooling components, etc.,” she said. “I always tell patients, ‘8-10 treatments is not uncommon. You’re going to have fewer hairs and thinner hairs, but it doesn’t mean that you’re going to have zero hairs in this area for the rest of your life.’ Set the expectation correctly.”
Patients should wear protective goggles if being treated in areas other than the face. “If being treated on the face, make sure they’re wearing appropriate protective eyewear such as laser safe eye shields. Those performing the treatment should wear surgical masks and use a smoke evacuator, as there are multiple known carcinogens and environmental toxins in the plume generated by laser hair removal,” she said (JAMA Dermatol. 2016;152[12]:1320-6).
Factors to consider in choosing treatment settings include hair color, the patient’s skin color, hair thickness, hair density, and body location. For example, the genital area may be more pigmented in some patients, and also may be more sensitive. “If you have thicker and darker hair it’s going to absorb more energy, so you have to adjust your settings,” Dr. Kelly said. She also avoids treating acutely tanned patients. “What you don’t want is for a tanned patient have a complication. I’d rather have them wait 2 or 3 weeks and come back. Sometimes it frustrates them a little, but it is safer.”
At the start of each procedure, Dr. Kelly delivers a couple of pulses then asks patients how uncomfortable they are on a scale from 1 to 10. “It often will vary,” she said. “Even if I’ve seen a patient for 10 treatments, some days it will hurt a little more than others. If the patient says it hurts a lot more than it normally does, you need to stop and think. That tells you that something is not right. They might be too tanned, or perhaps the [device] settings are wrong or the laser’s not functioning properly. Monitor the skin response. It takes time to see the final skin response, so wait before adjusting the energy. You want to see mild redness or mild follicular response. People report a little bit of a burning sensation.”
Postprocedure, she routinely applies a topical steroid such as betamethasone or clobetasol immediately after treatment. “That calms down the inflammatory response. If I see an area that I think is going to blister, I will apply the steroid multiple times until I see that response go away.” She asks patients about their pain level and typically applies ice to the treated area for 10 minutes before they leave the office, and they head home with after-care instructions, including a phone number where Dr. Kelly can be reached if patients have concerns. “I call my patients in the evening to ask how they’re doing, and if they have any questions.”
Dr. Kelly does not do laser hair removal inside the eye orbit or between the eyebrows, “because even with eye shields, you can have a problem,” she said. A potential outcome to be aware of is paradoxical hypertrichosis, or increased hair growth after laser hair removal estimated to occur in 0.6%-10% of patients. She discusses this with patients when consenting them. “Some people say this occurs in darker skin types, while others say it happens in people with thicker hair or thinner hair. Some of it occurs on the edges of the treatment area.” The treatment for paradoxical hypertrichosis is to continue laser hair removal and “try to push the energy just a little bit, but be cautious. It can be a difficult problem to resolve.”
Dr. Kelly has noticed a recent uptick at her practice in gender transition patients seeking hair removal procedures. “Removing facial and chest hair may be desirable, and may be covered by the patient’s health insurance,” she said. “Multiple treatments are required. A thick beard area needs to be approached cautiously.”
She referred to future advances in laser hair removal that may involve the use of topical agents to improve outcomes. For example, Sienna Biopharmaceuticals has developed Topical Photoparticle Therapy which, according to its website, uses “silver particles to absorb laser light and convert the light energy into heat to facilitate local tissue injury ... in the case of unwanted light or mixed pigment hair, which can’t be removed with lasers alone, [this process] targets the hair follicle.”
Dr. Kelly disclosed that she is an advisory consultant to Syneron Candela and Allergan. In addition, Allergan has provided drug products to Dr. Kelly for research purposes, while Solta Medical and ThermiRF have provided her with donated light sources for research or clinical use. Dr. Kelly has also received funding from the Sturge-Weber Foundation, the American Society for Laser Medicine and Surgery, and the National Institutes of Health.
[email protected]
EXPERT ANALYSIS FROM MOAS 2018
Reviving rural health care
Hospitalists have an important role to play
Health care in the United States has seen tremendous change in the last 2-3 decades, stemming from a dramatic push to contain spending, a call to action to improve quality and safety, and a boom in technology and medical advancement.
While the specialty of hospital medicine in the United States matured in response to these calls to action, it mostly flourished amidst – and as a result of – market consolidation, cost containment, the rise in the underinsured, and the flight of primary care from hospitals.
Changes in the health care industry have paralleled other parts of our society. Health care organizations, like schools, churches, theaters, parks, and sports teams, are part of the social fabric of communities. They provide stability to communities as employers, educators, social supporters, and the provision of services. It is no wonder then, that smaller communities, rural areas in particular, flourish or wither when one or more of these institutions, especially health care, fail them.
Health disparities result from any number of factors but particularly when communities are destabilized. The Robert Wood Johnson Foundation has studied this across the United States. For example, in the Twin Cities of Minneapolis–St. Paul, Minn., where I live, life expectancy varies by over 10 years along the interstate highway that runs through the metro area. Similarly, this disparity is seen between urban and rural Kentucky.
To be sure, the confounding social determinants of health and the mitigating strategies for the communities are different in urban Minneapolis than in Wolfe County, Kentucky. However, much of the work around health care reform (and therefore, hospital medicine) has centered around urban populations such as Minneapolis rather than rural populations such as Wolfe County. While 80% of the U.S. population lives in urban centers, that still means that 1 in 5 people live in rural America – spread across 97% of the U.S. land mass. These rural populations are exceedingly diverse, and warrant exceedingly diverse solutions.
Eighteen years ago, when I started my career in hospital medicine, I would never have thought I would be a spokesman for rural care. I identified as an urban academic hospitalist at a safety net hospital known for serving the urban poor and diverse refugee populations. But I had not anticipated mergers involving urban and rural hospitals, nor our resulting responsibility for staffing several critical access hospitals in another state.
It was hard in the beginning to recruit hospitalists to rural areas, so I worked in those areas myself, and experienced the rich practice in nonurban centers. As our partners also joined in our efforts to staff these hospitals, they had similar experiences. Now we can’t keep physicians away. That is not to say that the challenges are over.
Since 2010, 26 states lost rural hospitals – over 80 hospitals in total. High premiums in the individual health insurance market have driven healthy people out of risk pools, pushed payers out of the market, driving premiums higher still, resulting in coverage deserts. Consolidation and alignment with urban and national health care organizations initially brought hope to cash-strapped rural hospitals. Instead of improving local access, however, referrals to urban centers drained rural hospitals of their sources of income.
Economic instability has further destabilized communities. Rural America is exceptionally diverse, and has higher rates of poverty and the working poor, a shrinking job market that still hasn’t recovered from the 2008 recession, and higher rates of disability when compared to urban America. Do I even need to mention the rural opioid epidemic? Or the rural physician crisis, with a dwindling 12% of primary care and 8% of specialty care in these communities?
There is hope. During a late-night text conversation with a millennial nocturnist who splits his time between large and small hospitals, I received this message at 11:42 p.m.: “I think I feel more appreciated/valued/respected out here. You know how it is at the smaller hospitals.”
This was a comment the young hospitalist made after he shared with me that, lately, he had been in a “funk.” Innovations such as telemedicine have brought balance to overworked rural family doctors and excitement to young, tech savvy hospitalists. Opportunities to educate rural nurses and increase the level of care, keeping patients local, have excited academic hospitalists and rural CFOs alike. For a physician in a high burnout specialty, a long peaceful drive through the country might be just what’s needed to encourage a few moments of mindfulness.
Many of our urban health systems have combined with rural ones. It’s time to embrace it. Ignoring the health disparities in rural America divides us and diminishes essential parts of our health care system. Calling the hospitals our patients are referred from “OSH” (Outside Hospitals) will only perpetuate that.
Hospitalists have an opportunity to play an important role in stabilizing rural communities, reviving rural health systems, and providing local access to health care. Let’s embrace this opportunity to make a lasting impact on this frontier in hospital medicine.
Dr. Siy is chair of the department of hospital medicine at HealthPartners in Minneapolis–St. Paul, Minn., and a member of the SHM board of directors.
Hospitalists have an important role to play
Hospitalists have an important role to play
Health care in the United States has seen tremendous change in the last 2-3 decades, stemming from a dramatic push to contain spending, a call to action to improve quality and safety, and a boom in technology and medical advancement.
While the specialty of hospital medicine in the United States matured in response to these calls to action, it mostly flourished amidst – and as a result of – market consolidation, cost containment, the rise in the underinsured, and the flight of primary care from hospitals.
Changes in the health care industry have paralleled other parts of our society. Health care organizations, like schools, churches, theaters, parks, and sports teams, are part of the social fabric of communities. They provide stability to communities as employers, educators, social supporters, and the provision of services. It is no wonder then, that smaller communities, rural areas in particular, flourish or wither when one or more of these institutions, especially health care, fail them.
Health disparities result from any number of factors but particularly when communities are destabilized. The Robert Wood Johnson Foundation has studied this across the United States. For example, in the Twin Cities of Minneapolis–St. Paul, Minn., where I live, life expectancy varies by over 10 years along the interstate highway that runs through the metro area. Similarly, this disparity is seen between urban and rural Kentucky.
To be sure, the confounding social determinants of health and the mitigating strategies for the communities are different in urban Minneapolis than in Wolfe County, Kentucky. However, much of the work around health care reform (and therefore, hospital medicine) has centered around urban populations such as Minneapolis rather than rural populations such as Wolfe County. While 80% of the U.S. population lives in urban centers, that still means that 1 in 5 people live in rural America – spread across 97% of the U.S. land mass. These rural populations are exceedingly diverse, and warrant exceedingly diverse solutions.
Eighteen years ago, when I started my career in hospital medicine, I would never have thought I would be a spokesman for rural care. I identified as an urban academic hospitalist at a safety net hospital known for serving the urban poor and diverse refugee populations. But I had not anticipated mergers involving urban and rural hospitals, nor our resulting responsibility for staffing several critical access hospitals in another state.
It was hard in the beginning to recruit hospitalists to rural areas, so I worked in those areas myself, and experienced the rich practice in nonurban centers. As our partners also joined in our efforts to staff these hospitals, they had similar experiences. Now we can’t keep physicians away. That is not to say that the challenges are over.
Since 2010, 26 states lost rural hospitals – over 80 hospitals in total. High premiums in the individual health insurance market have driven healthy people out of risk pools, pushed payers out of the market, driving premiums higher still, resulting in coverage deserts. Consolidation and alignment with urban and national health care organizations initially brought hope to cash-strapped rural hospitals. Instead of improving local access, however, referrals to urban centers drained rural hospitals of their sources of income.
Economic instability has further destabilized communities. Rural America is exceptionally diverse, and has higher rates of poverty and the working poor, a shrinking job market that still hasn’t recovered from the 2008 recession, and higher rates of disability when compared to urban America. Do I even need to mention the rural opioid epidemic? Or the rural physician crisis, with a dwindling 12% of primary care and 8% of specialty care in these communities?
There is hope. During a late-night text conversation with a millennial nocturnist who splits his time between large and small hospitals, I received this message at 11:42 p.m.: “I think I feel more appreciated/valued/respected out here. You know how it is at the smaller hospitals.”
This was a comment the young hospitalist made after he shared with me that, lately, he had been in a “funk.” Innovations such as telemedicine have brought balance to overworked rural family doctors and excitement to young, tech savvy hospitalists. Opportunities to educate rural nurses and increase the level of care, keeping patients local, have excited academic hospitalists and rural CFOs alike. For a physician in a high burnout specialty, a long peaceful drive through the country might be just what’s needed to encourage a few moments of mindfulness.
Many of our urban health systems have combined with rural ones. It’s time to embrace it. Ignoring the health disparities in rural America divides us and diminishes essential parts of our health care system. Calling the hospitals our patients are referred from “OSH” (Outside Hospitals) will only perpetuate that.
Hospitalists have an opportunity to play an important role in stabilizing rural communities, reviving rural health systems, and providing local access to health care. Let’s embrace this opportunity to make a lasting impact on this frontier in hospital medicine.
Dr. Siy is chair of the department of hospital medicine at HealthPartners in Minneapolis–St. Paul, Minn., and a member of the SHM board of directors.
Health care in the United States has seen tremendous change in the last 2-3 decades, stemming from a dramatic push to contain spending, a call to action to improve quality and safety, and a boom in technology and medical advancement.
While the specialty of hospital medicine in the United States matured in response to these calls to action, it mostly flourished amidst – and as a result of – market consolidation, cost containment, the rise in the underinsured, and the flight of primary care from hospitals.
Changes in the health care industry have paralleled other parts of our society. Health care organizations, like schools, churches, theaters, parks, and sports teams, are part of the social fabric of communities. They provide stability to communities as employers, educators, social supporters, and the provision of services. It is no wonder then, that smaller communities, rural areas in particular, flourish or wither when one or more of these institutions, especially health care, fail them.
Health disparities result from any number of factors but particularly when communities are destabilized. The Robert Wood Johnson Foundation has studied this across the United States. For example, in the Twin Cities of Minneapolis–St. Paul, Minn., where I live, life expectancy varies by over 10 years along the interstate highway that runs through the metro area. Similarly, this disparity is seen between urban and rural Kentucky.
To be sure, the confounding social determinants of health and the mitigating strategies for the communities are different in urban Minneapolis than in Wolfe County, Kentucky. However, much of the work around health care reform (and therefore, hospital medicine) has centered around urban populations such as Minneapolis rather than rural populations such as Wolfe County. While 80% of the U.S. population lives in urban centers, that still means that 1 in 5 people live in rural America – spread across 97% of the U.S. land mass. These rural populations are exceedingly diverse, and warrant exceedingly diverse solutions.
Eighteen years ago, when I started my career in hospital medicine, I would never have thought I would be a spokesman for rural care. I identified as an urban academic hospitalist at a safety net hospital known for serving the urban poor and diverse refugee populations. But I had not anticipated mergers involving urban and rural hospitals, nor our resulting responsibility for staffing several critical access hospitals in another state.
It was hard in the beginning to recruit hospitalists to rural areas, so I worked in those areas myself, and experienced the rich practice in nonurban centers. As our partners also joined in our efforts to staff these hospitals, they had similar experiences. Now we can’t keep physicians away. That is not to say that the challenges are over.
Since 2010, 26 states lost rural hospitals – over 80 hospitals in total. High premiums in the individual health insurance market have driven healthy people out of risk pools, pushed payers out of the market, driving premiums higher still, resulting in coverage deserts. Consolidation and alignment with urban and national health care organizations initially brought hope to cash-strapped rural hospitals. Instead of improving local access, however, referrals to urban centers drained rural hospitals of their sources of income.
Economic instability has further destabilized communities. Rural America is exceptionally diverse, and has higher rates of poverty and the working poor, a shrinking job market that still hasn’t recovered from the 2008 recession, and higher rates of disability when compared to urban America. Do I even need to mention the rural opioid epidemic? Or the rural physician crisis, with a dwindling 12% of primary care and 8% of specialty care in these communities?
There is hope. During a late-night text conversation with a millennial nocturnist who splits his time between large and small hospitals, I received this message at 11:42 p.m.: “I think I feel more appreciated/valued/respected out here. You know how it is at the smaller hospitals.”
This was a comment the young hospitalist made after he shared with me that, lately, he had been in a “funk.” Innovations such as telemedicine have brought balance to overworked rural family doctors and excitement to young, tech savvy hospitalists. Opportunities to educate rural nurses and increase the level of care, keeping patients local, have excited academic hospitalists and rural CFOs alike. For a physician in a high burnout specialty, a long peaceful drive through the country might be just what’s needed to encourage a few moments of mindfulness.
Many of our urban health systems have combined with rural ones. It’s time to embrace it. Ignoring the health disparities in rural America divides us and diminishes essential parts of our health care system. Calling the hospitals our patients are referred from “OSH” (Outside Hospitals) will only perpetuate that.
Hospitalists have an opportunity to play an important role in stabilizing rural communities, reviving rural health systems, and providing local access to health care. Let’s embrace this opportunity to make a lasting impact on this frontier in hospital medicine.
Dr. Siy is chair of the department of hospital medicine at HealthPartners in Minneapolis–St. Paul, Minn., and a member of the SHM board of directors.
Specialist offers pain medication pro tips for rheumatologists
LAS VEGAS – Be prepared to prescribe pain medications off label. Understand that some of these drugs are double- or even triple-action, although the three-in-ones aren’t necessarily the best option. And beware of prescribing both opioid painkillers and benzodiazepines over the long term.
Xavier Jimenez, MD, a psychiatrist and chronic pain specialist at the Cleveland Clinic, offered these held by Global Academy for Medical Education.
Here’s a closer look at his tips:
• “Avoid chronic opioid therapy for the most part because of the preponderance of negative effects,” Dr. Jimenez said. “You should also try as best as possible to avoid chronic benzodiazepine therapy, which hasn’t gotten as much media attention but has been linked to all sorts of negative outcomes.”
As he described it, a 2010 study (Pain Med. 2010 Jun;11[6]:805-14) revealed that “benzodiazepines predict opioid use better than pain itself. One thing you can do [to help patients] is start to remove the benzodiazepines.”
Are benzodiazepines even useful for rheumatic conditions? A 2012 Cochrane review of the use of diazepam and triazolam found that they “do not appear to be beneficial in improving pain over 24 hours or 1 week” (Cochrane Database Syst Rev. 2012 Jan 18;1:CD008922. doi: 10.1002/14651858.CD008922.pub2).
• When it comes to choosing medications for pain, “there isn’t really a good textbook algorithm. You’ll have to be creative,” he said. “There are a lot of off-label uses going on here. It’s the norm, not the exception.”
• Some painkillers can have antidepressant, anxiolytic (anti-anxiety) or analgesic effects, and a few like duloxetine (Cymbalta) have “double” or “triple action,” Dr. Jimenez said. Some doctors may be tempted to immediately go for something like duloxetine, but he questioned whether “it’s really that simple.”
“That’s done and is effective for a large proportion of these patients, but not everyone. You will have a lot of patients who’ve tried these and not benefited.”
Is Cymbalta appropriate for rheumatic disease? It may be, at least for chronic knee pain due to osteoarthritis: A 2013 review found that three studies supported its pain-relieving properties relative to placebo at about 4 weeks (Ther Adv Musculoskelet Dis. 2013 Dec;5[6]:291-304).
• Consider treating unresolved anxiety, which Dr. Jimenez said he sees more often in moderate and refractory chronic pain. “No one’s asking you to become psychiatrists,” he said, “but I imagine you are asked to act as psychiatrists.”
Researchers continue to explore connections between anxiety and rheumatic disease. A 2016 study of 56 patients with rheumatoid arthritis (RA) over 1 year found that “inflated [28-joint Disease Activity Score] despite well controlled inflammatory disease markers may indicate significant psychological morbidity and related non-inflammatory pain, rather than true disease activity” (BMC Musculoskelet Disord. 2016;17:155).
• Among the many painkiller options are: Gabapentin (“widely used, relatively safe”), pregabalin (keep an eye on kidney values) and topiramate/Topamax (“a pretty decent medication if you’ve got someone who’s not too depressed,” but watch out for the brain-dulling effect that’s spawned a nickname for the drug: “Dopamax”).
• Cannabinoids aren’t ready for prime time as a pain treatment. “Generally, the message here is ‘not yet,’ ” Dr. Jimenez said. “We don’t have enough compelling evidence to suggest cannabinoids are effective, uniformly or across rheumatic diseases. We know much more about the deficits than the benefits.”
What about rheumatic disease and cannabinoids specifically? A 2018 review of research said “preliminary clinical trials have explored the effects of cannabis on rheumatoid arthritis, osteoarthritis, and fibromyalgia; preliminary evidence has also found an association between the cannabinoid system and other rheumatic conditions, including systemic sclerosis and juvenile idiopathic arthritis.”
However, the report says, evidence so far is insufficient to recommend cannabis in rheumatic disease (Nat Rev Rheumatol. 2018;14:488-98).
For now, Dr. Jimenez advised: “Sit tight and wait.”
Dr. Jimenez reported no relevant disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Be prepared to prescribe pain medications off label. Understand that some of these drugs are double- or even triple-action, although the three-in-ones aren’t necessarily the best option. And beware of prescribing both opioid painkillers and benzodiazepines over the long term.
Xavier Jimenez, MD, a psychiatrist and chronic pain specialist at the Cleveland Clinic, offered these held by Global Academy for Medical Education.
Here’s a closer look at his tips:
• “Avoid chronic opioid therapy for the most part because of the preponderance of negative effects,” Dr. Jimenez said. “You should also try as best as possible to avoid chronic benzodiazepine therapy, which hasn’t gotten as much media attention but has been linked to all sorts of negative outcomes.”
As he described it, a 2010 study (Pain Med. 2010 Jun;11[6]:805-14) revealed that “benzodiazepines predict opioid use better than pain itself. One thing you can do [to help patients] is start to remove the benzodiazepines.”
Are benzodiazepines even useful for rheumatic conditions? A 2012 Cochrane review of the use of diazepam and triazolam found that they “do not appear to be beneficial in improving pain over 24 hours or 1 week” (Cochrane Database Syst Rev. 2012 Jan 18;1:CD008922. doi: 10.1002/14651858.CD008922.pub2).
• When it comes to choosing medications for pain, “there isn’t really a good textbook algorithm. You’ll have to be creative,” he said. “There are a lot of off-label uses going on here. It’s the norm, not the exception.”
• Some painkillers can have antidepressant, anxiolytic (anti-anxiety) or analgesic effects, and a few like duloxetine (Cymbalta) have “double” or “triple action,” Dr. Jimenez said. Some doctors may be tempted to immediately go for something like duloxetine, but he questioned whether “it’s really that simple.”
“That’s done and is effective for a large proportion of these patients, but not everyone. You will have a lot of patients who’ve tried these and not benefited.”
Is Cymbalta appropriate for rheumatic disease? It may be, at least for chronic knee pain due to osteoarthritis: A 2013 review found that three studies supported its pain-relieving properties relative to placebo at about 4 weeks (Ther Adv Musculoskelet Dis. 2013 Dec;5[6]:291-304).
• Consider treating unresolved anxiety, which Dr. Jimenez said he sees more often in moderate and refractory chronic pain. “No one’s asking you to become psychiatrists,” he said, “but I imagine you are asked to act as psychiatrists.”
Researchers continue to explore connections between anxiety and rheumatic disease. A 2016 study of 56 patients with rheumatoid arthritis (RA) over 1 year found that “inflated [28-joint Disease Activity Score] despite well controlled inflammatory disease markers may indicate significant psychological morbidity and related non-inflammatory pain, rather than true disease activity” (BMC Musculoskelet Disord. 2016;17:155).
• Among the many painkiller options are: Gabapentin (“widely used, relatively safe”), pregabalin (keep an eye on kidney values) and topiramate/Topamax (“a pretty decent medication if you’ve got someone who’s not too depressed,” but watch out for the brain-dulling effect that’s spawned a nickname for the drug: “Dopamax”).
• Cannabinoids aren’t ready for prime time as a pain treatment. “Generally, the message here is ‘not yet,’ ” Dr. Jimenez said. “We don’t have enough compelling evidence to suggest cannabinoids are effective, uniformly or across rheumatic diseases. We know much more about the deficits than the benefits.”
What about rheumatic disease and cannabinoids specifically? A 2018 review of research said “preliminary clinical trials have explored the effects of cannabis on rheumatoid arthritis, osteoarthritis, and fibromyalgia; preliminary evidence has also found an association between the cannabinoid system and other rheumatic conditions, including systemic sclerosis and juvenile idiopathic arthritis.”
However, the report says, evidence so far is insufficient to recommend cannabis in rheumatic disease (Nat Rev Rheumatol. 2018;14:488-98).
For now, Dr. Jimenez advised: “Sit tight and wait.”
Dr. Jimenez reported no relevant disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Be prepared to prescribe pain medications off label. Understand that some of these drugs are double- or even triple-action, although the three-in-ones aren’t necessarily the best option. And beware of prescribing both opioid painkillers and benzodiazepines over the long term.
Xavier Jimenez, MD, a psychiatrist and chronic pain specialist at the Cleveland Clinic, offered these held by Global Academy for Medical Education.
Here’s a closer look at his tips:
• “Avoid chronic opioid therapy for the most part because of the preponderance of negative effects,” Dr. Jimenez said. “You should also try as best as possible to avoid chronic benzodiazepine therapy, which hasn’t gotten as much media attention but has been linked to all sorts of negative outcomes.”
As he described it, a 2010 study (Pain Med. 2010 Jun;11[6]:805-14) revealed that “benzodiazepines predict opioid use better than pain itself. One thing you can do [to help patients] is start to remove the benzodiazepines.”
Are benzodiazepines even useful for rheumatic conditions? A 2012 Cochrane review of the use of diazepam and triazolam found that they “do not appear to be beneficial in improving pain over 24 hours or 1 week” (Cochrane Database Syst Rev. 2012 Jan 18;1:CD008922. doi: 10.1002/14651858.CD008922.pub2).
• When it comes to choosing medications for pain, “there isn’t really a good textbook algorithm. You’ll have to be creative,” he said. “There are a lot of off-label uses going on here. It’s the norm, not the exception.”
• Some painkillers can have antidepressant, anxiolytic (anti-anxiety) or analgesic effects, and a few like duloxetine (Cymbalta) have “double” or “triple action,” Dr. Jimenez said. Some doctors may be tempted to immediately go for something like duloxetine, but he questioned whether “it’s really that simple.”
“That’s done and is effective for a large proportion of these patients, but not everyone. You will have a lot of patients who’ve tried these and not benefited.”
Is Cymbalta appropriate for rheumatic disease? It may be, at least for chronic knee pain due to osteoarthritis: A 2013 review found that three studies supported its pain-relieving properties relative to placebo at about 4 weeks (Ther Adv Musculoskelet Dis. 2013 Dec;5[6]:291-304).
• Consider treating unresolved anxiety, which Dr. Jimenez said he sees more often in moderate and refractory chronic pain. “No one’s asking you to become psychiatrists,” he said, “but I imagine you are asked to act as psychiatrists.”
Researchers continue to explore connections between anxiety and rheumatic disease. A 2016 study of 56 patients with rheumatoid arthritis (RA) over 1 year found that “inflated [28-joint Disease Activity Score] despite well controlled inflammatory disease markers may indicate significant psychological morbidity and related non-inflammatory pain, rather than true disease activity” (BMC Musculoskelet Disord. 2016;17:155).
• Among the many painkiller options are: Gabapentin (“widely used, relatively safe”), pregabalin (keep an eye on kidney values) and topiramate/Topamax (“a pretty decent medication if you’ve got someone who’s not too depressed,” but watch out for the brain-dulling effect that’s spawned a nickname for the drug: “Dopamax”).
• Cannabinoids aren’t ready for prime time as a pain treatment. “Generally, the message here is ‘not yet,’ ” Dr. Jimenez said. “We don’t have enough compelling evidence to suggest cannabinoids are effective, uniformly or across rheumatic diseases. We know much more about the deficits than the benefits.”
What about rheumatic disease and cannabinoids specifically? A 2018 review of research said “preliminary clinical trials have explored the effects of cannabis on rheumatoid arthritis, osteoarthritis, and fibromyalgia; preliminary evidence has also found an association between the cannabinoid system and other rheumatic conditions, including systemic sclerosis and juvenile idiopathic arthritis.”
However, the report says, evidence so far is insufficient to recommend cannabis in rheumatic disease (Nat Rev Rheumatol. 2018;14:488-98).
For now, Dr. Jimenez advised: “Sit tight and wait.”
Dr. Jimenez reported no relevant disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
AYA cancer: Bridging the divide
and older adult patients, a trend that has been going on for decades. But clinicians and researchers are getting serious about an important question: Why?
“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist, and director of pediatric bone marrow transplantation at Cleveland Clinic Children’s Hospital, Ohio, said in an interview.
He is referring to the cancers that affect adolescents and young adults (AYAs), who are broadly defined as patients aged 15-39 years.
“A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults; biology may be different in the adolescent and young adult patients, which may lead to different outcomes,” Dr. Hanna said.
In addition, the psychosocial needs in this age group differ vastly from those of other groups, he said.
“Many of these patients are in college or have just started their families, so we have to pay attention more to financial toxicities and fertility, for example,” he said.
Another factor that likely contributes to the disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs. That’s a point on which Dr. Hanna and many other experts agree.
A recent series of articles published in Blood addressed these and other issues, including whether AYAs with ALL or aggressive B-cell non-Hodgkin lymphomas (NHLs) should be treated as children or adults, treatment strategies for those with acute myeloid leukemias, management of Hodgkin lymphoma, and psychosocial challenges and health-related quality of life (QOL) of AYAs with hematologic malignancies.
“Hematological malignancies occurring in AYAs represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population,” Jorge Cortes, MD, an assistant editor for Blood, wrote in an introduction to the series.
“Unfortunately, not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs frequently centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults. Clinical trials specifically designed for AYAs are scanty,” noted Dr. Cortes, who directs the chronic myeloid leukemia (CML) and acute myeloid leukemia programs (AML) at the University of Texas MD Anderson Cancer Center, Houston.
Treatment approach and setting
In the Blood article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15-20 years is supported by numerous studies, and that in young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” as they have been shown to dramatically improve outcomes, with long-term survival rates nearing 70% (2018;132:351-61).
Patients in these age groups require specific programs that take into account factors such as care access and trial access, increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.
Kristen O’Dwyer, MD, and her colleagues, in their article on AML treatment in AYAs, argue that based on “the distinguishing characteristics of AYAs with AML,” neither the pediatric nor adult approaches are ideally suited for them.
Rather, AYA-specific approaches merit consideration, they concluded (Blood 2018;132:362-68).
Similarly, Kieron Dunleavy, MD, and Thomas G. Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that a “remarkable divide” in the treatment of patients under age 18 years with lymphoma versus their young adult counterparts underscores the need for collaboration in developing consensus regarding treatment of AYAs (Blood 2018;132:369-75).
But recent findings from a study by Paul C. Nathan, MD, and his colleagues focuses more on where that treatment should take place (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy119).
The study provides new insights into the understanding of treatment differences for adolescents seen in pediatric vs. adult cancer facilities. And the findings suggest that the trade-off for improved outcomes among those treated in the pediatric setting – as emerging literature demonstrates – is higher resource use and cost, Helen M. Parsons, PhD, and her colleagues wrote in an accompanying editorial (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy123).
Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the cost of care was higher when treatment took place in a pediatric setting vs. an adult institution. This was driven in part by higher hospitalization rates and longer hospital stays, the investigators found.
“Additionally, adolescents treated in the pediatric setting tended to seek more [emergency department] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship,” Dr. Parsons and her colleagues wrote.
This was true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.
The findings of higher inpatient days in the pediatric setting is not surprising given that induction therapies for pediatric ALL are generally more complex and intensive than therapies commonly used in adults with ALL, and given that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.
“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase ... more work on this topic is needed to more fully understand these patterns,” they wrote, adding that “the finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.”
Disease and developmental biology
As Dr. Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and may have different outcomes with the same treatments.
For example, the biology of AML is known to change with age, Dr. Dwyer and her colleagues said, explaining that a recent European study showed that in 5,564 patients with de novo AML, the frequency of favorable cytogenetics was low in infants, increased in children and young adults, and decreased again in middle age and older age (Cancer. 2016 Dec 15;122[24]:3821-30).
“Normal karyotype increases in prevalence from 13.7% in infants to approximately 25% in children, 44% in AYAs, and 50% in adults. Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr. Dwyer and her colleagues wrote, noting that it also is becoming more apparent that age influences the presence of AML-related molecular abnormalities.
The authors argue that recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”
Dr. Boissel and Dr. Baruchel also note that the “black hole” of understanding of ALL biology in AYAs that characterized the last 15 years has been “nearly brought to light and revealed a continuum between childhood and adult ALL.”
One example of this involves data from the NOPHO-ALL-2008 trial, showing that the proportion of patients with intrachromosomal amplification of the long arm of chromosome 21 (iAMP21), which is a rare event occurring in about 2% of children with ALL, is more frequent in older children and adolescents and is associated with higher relapse risk that is only partially diminished by intensified treatment.
In NOPHO-2008, iAMP21 occurred in 1.5% of patients aged 1-9 years, 5.8% of those aged 10-17 years, and 12% of those aged 17-45 years. The authors provided numerous other examples of such age-related differences in disease biology and concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
Psychosocial factors
The “financial toxicity” mentioned by Dr. Hanna – the high cost of care, lost work time, and delays in reaching educational and career goals, for example – is a major factor that must be addressed in this population, but there are also many others.
“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John M. Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, N.C., said in an interview.
These patients not only have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, but in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added.
“Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... These are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so,” he said.
In a 2014 study, he and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life. The latter finding was surprising, and highlights the “critical importance” of the social dimension in AYAs’ lives.
“Patient after patient will say ‘I found out who my real friends are,’ ” Dr. Salsman said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”
Dr. Salsman and his colleagues are using those findings to develop interventions that can maximize self care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves.
A randomized controlled pilot study incorporating social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions, for example, is underway.
Another intervention targets emotional well-being via web-based tools to increase positive affect. A proof-of-concept study showed that the approach is feasible and well received, and efforts are underway to plan a larger-scale randomized controlled trial, he said.
Dr. Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital.
PRISM was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis, and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
Trial enrollment
In his editorial introducing the Blood series on AYAs and cancer, Dr. Cortes noted a paucity of clinical trials specifically designed for this population.
“At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, adding that “enrollment of AYAs in clinical trials in cancer in general has been suboptimal at best.”
The dismal numbers with respect to enrollment of AYAs with cancer in clinical trials may be related in part to treatment setting, Dr. Salsman said.
Data suggest that the majority of AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers, where the bulk of research is being done, he explained.
The bottom line is that more research involving AYAs is needed, as is greater understanding of why enrollment is so much lower among AYA patients, Dr. Hanna said, noting that in 2017, The American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FOCR) released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.
Individuals aged 12 years and older should routinely be included in such trials as their drug metabolism is similar to that of adults, and inclusion of younger patients may also be appropriate if they are part of the population impacted by the disease, depending on specific disease biology, action of the drug, and available safety information, the organizations said.
Officials at the Food and Drug Administration are considering that possibility, Dr. Hanna said.
Attention to the disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups, has definitely increased in recent years, Dr. Salsman added, noting that in addition to ASCO and FOCR, several other organizations are working to address the problem.
About 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population; the Institute of Medicine held a forum on the care of AYAs with cancer; and the National Cancer Institute (NCI) held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology, he noted.
An article in Cancer provides a summary of the progress toward the priorities identified during the NCI meeting, which convened five working groups to address various topics, including clinical trial enrollment (Cancer. 2016 Apr 1;122[7]:988-99).
Dr. Hanna added that groups such as the Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now.
“One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically coordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.
In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr. Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.
Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.
What’s next?
Among the recommendations of the authors of the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams with involvement of multidisciplinary teams.
Many centers are already working on models for collaborative care, Dr. Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in “getting stakeholders on the same page, helping them have a shared vision, and working to maximize improvements in outcomes.”
Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr. Hanna said. In the case of the community-powered advocacy organization Critical Mass, they succeeded in getting lawmakers to introduce a bill in the U.S. House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.
and older adult patients, a trend that has been going on for decades. But clinicians and researchers are getting serious about an important question: Why?
“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist, and director of pediatric bone marrow transplantation at Cleveland Clinic Children’s Hospital, Ohio, said in an interview.
He is referring to the cancers that affect adolescents and young adults (AYAs), who are broadly defined as patients aged 15-39 years.
“A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults; biology may be different in the adolescent and young adult patients, which may lead to different outcomes,” Dr. Hanna said.
In addition, the psychosocial needs in this age group differ vastly from those of other groups, he said.
“Many of these patients are in college or have just started their families, so we have to pay attention more to financial toxicities and fertility, for example,” he said.
Another factor that likely contributes to the disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs. That’s a point on which Dr. Hanna and many other experts agree.
A recent series of articles published in Blood addressed these and other issues, including whether AYAs with ALL or aggressive B-cell non-Hodgkin lymphomas (NHLs) should be treated as children or adults, treatment strategies for those with acute myeloid leukemias, management of Hodgkin lymphoma, and psychosocial challenges and health-related quality of life (QOL) of AYAs with hematologic malignancies.
“Hematological malignancies occurring in AYAs represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population,” Jorge Cortes, MD, an assistant editor for Blood, wrote in an introduction to the series.
“Unfortunately, not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs frequently centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults. Clinical trials specifically designed for AYAs are scanty,” noted Dr. Cortes, who directs the chronic myeloid leukemia (CML) and acute myeloid leukemia programs (AML) at the University of Texas MD Anderson Cancer Center, Houston.
Treatment approach and setting
In the Blood article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15-20 years is supported by numerous studies, and that in young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” as they have been shown to dramatically improve outcomes, with long-term survival rates nearing 70% (2018;132:351-61).
Patients in these age groups require specific programs that take into account factors such as care access and trial access, increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.
Kristen O’Dwyer, MD, and her colleagues, in their article on AML treatment in AYAs, argue that based on “the distinguishing characteristics of AYAs with AML,” neither the pediatric nor adult approaches are ideally suited for them.
Rather, AYA-specific approaches merit consideration, they concluded (Blood 2018;132:362-68).
Similarly, Kieron Dunleavy, MD, and Thomas G. Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that a “remarkable divide” in the treatment of patients under age 18 years with lymphoma versus their young adult counterparts underscores the need for collaboration in developing consensus regarding treatment of AYAs (Blood 2018;132:369-75).
But recent findings from a study by Paul C. Nathan, MD, and his colleagues focuses more on where that treatment should take place (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy119).
The study provides new insights into the understanding of treatment differences for adolescents seen in pediatric vs. adult cancer facilities. And the findings suggest that the trade-off for improved outcomes among those treated in the pediatric setting – as emerging literature demonstrates – is higher resource use and cost, Helen M. Parsons, PhD, and her colleagues wrote in an accompanying editorial (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy123).
Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the cost of care was higher when treatment took place in a pediatric setting vs. an adult institution. This was driven in part by higher hospitalization rates and longer hospital stays, the investigators found.
“Additionally, adolescents treated in the pediatric setting tended to seek more [emergency department] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship,” Dr. Parsons and her colleagues wrote.
This was true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.
The findings of higher inpatient days in the pediatric setting is not surprising given that induction therapies for pediatric ALL are generally more complex and intensive than therapies commonly used in adults with ALL, and given that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.
“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase ... more work on this topic is needed to more fully understand these patterns,” they wrote, adding that “the finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.”
Disease and developmental biology
As Dr. Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and may have different outcomes with the same treatments.
For example, the biology of AML is known to change with age, Dr. Dwyer and her colleagues said, explaining that a recent European study showed that in 5,564 patients with de novo AML, the frequency of favorable cytogenetics was low in infants, increased in children and young adults, and decreased again in middle age and older age (Cancer. 2016 Dec 15;122[24]:3821-30).
“Normal karyotype increases in prevalence from 13.7% in infants to approximately 25% in children, 44% in AYAs, and 50% in adults. Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr. Dwyer and her colleagues wrote, noting that it also is becoming more apparent that age influences the presence of AML-related molecular abnormalities.
The authors argue that recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”
Dr. Boissel and Dr. Baruchel also note that the “black hole” of understanding of ALL biology in AYAs that characterized the last 15 years has been “nearly brought to light and revealed a continuum between childhood and adult ALL.”
One example of this involves data from the NOPHO-ALL-2008 trial, showing that the proportion of patients with intrachromosomal amplification of the long arm of chromosome 21 (iAMP21), which is a rare event occurring in about 2% of children with ALL, is more frequent in older children and adolescents and is associated with higher relapse risk that is only partially diminished by intensified treatment.
In NOPHO-2008, iAMP21 occurred in 1.5% of patients aged 1-9 years, 5.8% of those aged 10-17 years, and 12% of those aged 17-45 years. The authors provided numerous other examples of such age-related differences in disease biology and concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
Psychosocial factors
The “financial toxicity” mentioned by Dr. Hanna – the high cost of care, lost work time, and delays in reaching educational and career goals, for example – is a major factor that must be addressed in this population, but there are also many others.
“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John M. Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, N.C., said in an interview.
These patients not only have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, but in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added.
“Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... These are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so,” he said.
In a 2014 study, he and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life. The latter finding was surprising, and highlights the “critical importance” of the social dimension in AYAs’ lives.
“Patient after patient will say ‘I found out who my real friends are,’ ” Dr. Salsman said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”
Dr. Salsman and his colleagues are using those findings to develop interventions that can maximize self care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves.
A randomized controlled pilot study incorporating social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions, for example, is underway.
Another intervention targets emotional well-being via web-based tools to increase positive affect. A proof-of-concept study showed that the approach is feasible and well received, and efforts are underway to plan a larger-scale randomized controlled trial, he said.
Dr. Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital.
PRISM was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis, and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
Trial enrollment
In his editorial introducing the Blood series on AYAs and cancer, Dr. Cortes noted a paucity of clinical trials specifically designed for this population.
“At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, adding that “enrollment of AYAs in clinical trials in cancer in general has been suboptimal at best.”
The dismal numbers with respect to enrollment of AYAs with cancer in clinical trials may be related in part to treatment setting, Dr. Salsman said.
Data suggest that the majority of AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers, where the bulk of research is being done, he explained.
The bottom line is that more research involving AYAs is needed, as is greater understanding of why enrollment is so much lower among AYA patients, Dr. Hanna said, noting that in 2017, The American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FOCR) released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.
Individuals aged 12 years and older should routinely be included in such trials as their drug metabolism is similar to that of adults, and inclusion of younger patients may also be appropriate if they are part of the population impacted by the disease, depending on specific disease biology, action of the drug, and available safety information, the organizations said.
Officials at the Food and Drug Administration are considering that possibility, Dr. Hanna said.
Attention to the disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups, has definitely increased in recent years, Dr. Salsman added, noting that in addition to ASCO and FOCR, several other organizations are working to address the problem.
About 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population; the Institute of Medicine held a forum on the care of AYAs with cancer; and the National Cancer Institute (NCI) held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology, he noted.
An article in Cancer provides a summary of the progress toward the priorities identified during the NCI meeting, which convened five working groups to address various topics, including clinical trial enrollment (Cancer. 2016 Apr 1;122[7]:988-99).
Dr. Hanna added that groups such as the Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now.
“One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically coordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.
In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr. Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.
Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.
What’s next?
Among the recommendations of the authors of the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams with involvement of multidisciplinary teams.
Many centers are already working on models for collaborative care, Dr. Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in “getting stakeholders on the same page, helping them have a shared vision, and working to maximize improvements in outcomes.”
Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr. Hanna said. In the case of the community-powered advocacy organization Critical Mass, they succeeded in getting lawmakers to introduce a bill in the U.S. House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.
and older adult patients, a trend that has been going on for decades. But clinicians and researchers are getting serious about an important question: Why?
“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist, and director of pediatric bone marrow transplantation at Cleveland Clinic Children’s Hospital, Ohio, said in an interview.
He is referring to the cancers that affect adolescents and young adults (AYAs), who are broadly defined as patients aged 15-39 years.
“A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults; biology may be different in the adolescent and young adult patients, which may lead to different outcomes,” Dr. Hanna said.
In addition, the psychosocial needs in this age group differ vastly from those of other groups, he said.
“Many of these patients are in college or have just started their families, so we have to pay attention more to financial toxicities and fertility, for example,” he said.
Another factor that likely contributes to the disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs. That’s a point on which Dr. Hanna and many other experts agree.
A recent series of articles published in Blood addressed these and other issues, including whether AYAs with ALL or aggressive B-cell non-Hodgkin lymphomas (NHLs) should be treated as children or adults, treatment strategies for those with acute myeloid leukemias, management of Hodgkin lymphoma, and psychosocial challenges and health-related quality of life (QOL) of AYAs with hematologic malignancies.
“Hematological malignancies occurring in AYAs represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population,” Jorge Cortes, MD, an assistant editor for Blood, wrote in an introduction to the series.
“Unfortunately, not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs frequently centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults. Clinical trials specifically designed for AYAs are scanty,” noted Dr. Cortes, who directs the chronic myeloid leukemia (CML) and acute myeloid leukemia programs (AML) at the University of Texas MD Anderson Cancer Center, Houston.
Treatment approach and setting
In the Blood article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15-20 years is supported by numerous studies, and that in young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” as they have been shown to dramatically improve outcomes, with long-term survival rates nearing 70% (2018;132:351-61).
Patients in these age groups require specific programs that take into account factors such as care access and trial access, increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.
Kristen O’Dwyer, MD, and her colleagues, in their article on AML treatment in AYAs, argue that based on “the distinguishing characteristics of AYAs with AML,” neither the pediatric nor adult approaches are ideally suited for them.
Rather, AYA-specific approaches merit consideration, they concluded (Blood 2018;132:362-68).
Similarly, Kieron Dunleavy, MD, and Thomas G. Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that a “remarkable divide” in the treatment of patients under age 18 years with lymphoma versus their young adult counterparts underscores the need for collaboration in developing consensus regarding treatment of AYAs (Blood 2018;132:369-75).
But recent findings from a study by Paul C. Nathan, MD, and his colleagues focuses more on where that treatment should take place (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy119).
The study provides new insights into the understanding of treatment differences for adolescents seen in pediatric vs. adult cancer facilities. And the findings suggest that the trade-off for improved outcomes among those treated in the pediatric setting – as emerging literature demonstrates – is higher resource use and cost, Helen M. Parsons, PhD, and her colleagues wrote in an accompanying editorial (J Natl Cancer Inst. 2018 Jul 19. doi: 10.1093/jnci/djy123).
Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the cost of care was higher when treatment took place in a pediatric setting vs. an adult institution. This was driven in part by higher hospitalization rates and longer hospital stays, the investigators found.
“Additionally, adolescents treated in the pediatric setting tended to seek more [emergency department] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship,” Dr. Parsons and her colleagues wrote.
This was true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.
The findings of higher inpatient days in the pediatric setting is not surprising given that induction therapies for pediatric ALL are generally more complex and intensive than therapies commonly used in adults with ALL, and given that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.
“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase ... more work on this topic is needed to more fully understand these patterns,” they wrote, adding that “the finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.”
Disease and developmental biology
As Dr. Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and may have different outcomes with the same treatments.
For example, the biology of AML is known to change with age, Dr. Dwyer and her colleagues said, explaining that a recent European study showed that in 5,564 patients with de novo AML, the frequency of favorable cytogenetics was low in infants, increased in children and young adults, and decreased again in middle age and older age (Cancer. 2016 Dec 15;122[24]:3821-30).
“Normal karyotype increases in prevalence from 13.7% in infants to approximately 25% in children, 44% in AYAs, and 50% in adults. Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr. Dwyer and her colleagues wrote, noting that it also is becoming more apparent that age influences the presence of AML-related molecular abnormalities.
The authors argue that recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”
Dr. Boissel and Dr. Baruchel also note that the “black hole” of understanding of ALL biology in AYAs that characterized the last 15 years has been “nearly brought to light and revealed a continuum between childhood and adult ALL.”
One example of this involves data from the NOPHO-ALL-2008 trial, showing that the proportion of patients with intrachromosomal amplification of the long arm of chromosome 21 (iAMP21), which is a rare event occurring in about 2% of children with ALL, is more frequent in older children and adolescents and is associated with higher relapse risk that is only partially diminished by intensified treatment.
In NOPHO-2008, iAMP21 occurred in 1.5% of patients aged 1-9 years, 5.8% of those aged 10-17 years, and 12% of those aged 17-45 years. The authors provided numerous other examples of such age-related differences in disease biology and concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
Psychosocial factors
The “financial toxicity” mentioned by Dr. Hanna – the high cost of care, lost work time, and delays in reaching educational and career goals, for example – is a major factor that must be addressed in this population, but there are also many others.
“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John M. Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, N.C., said in an interview.
These patients not only have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, but in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added.
“Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... These are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so,” he said.
In a 2014 study, he and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life. The latter finding was surprising, and highlights the “critical importance” of the social dimension in AYAs’ lives.
“Patient after patient will say ‘I found out who my real friends are,’ ” Dr. Salsman said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”
Dr. Salsman and his colleagues are using those findings to develop interventions that can maximize self care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves.
A randomized controlled pilot study incorporating social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions, for example, is underway.
Another intervention targets emotional well-being via web-based tools to increase positive affect. A proof-of-concept study showed that the approach is feasible and well received, and efforts are underway to plan a larger-scale randomized controlled trial, he said.
Dr. Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital.
PRISM was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis, and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
Trial enrollment
In his editorial introducing the Blood series on AYAs and cancer, Dr. Cortes noted a paucity of clinical trials specifically designed for this population.
“At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, adding that “enrollment of AYAs in clinical trials in cancer in general has been suboptimal at best.”
The dismal numbers with respect to enrollment of AYAs with cancer in clinical trials may be related in part to treatment setting, Dr. Salsman said.
Data suggest that the majority of AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers, where the bulk of research is being done, he explained.
The bottom line is that more research involving AYAs is needed, as is greater understanding of why enrollment is so much lower among AYA patients, Dr. Hanna said, noting that in 2017, The American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FOCR) released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.
Individuals aged 12 years and older should routinely be included in such trials as their drug metabolism is similar to that of adults, and inclusion of younger patients may also be appropriate if they are part of the population impacted by the disease, depending on specific disease biology, action of the drug, and available safety information, the organizations said.
Officials at the Food and Drug Administration are considering that possibility, Dr. Hanna said.
Attention to the disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups, has definitely increased in recent years, Dr. Salsman added, noting that in addition to ASCO and FOCR, several other organizations are working to address the problem.
About 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population; the Institute of Medicine held a forum on the care of AYAs with cancer; and the National Cancer Institute (NCI) held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology, he noted.
An article in Cancer provides a summary of the progress toward the priorities identified during the NCI meeting, which convened five working groups to address various topics, including clinical trial enrollment (Cancer. 2016 Apr 1;122[7]:988-99).
Dr. Hanna added that groups such as the Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now.
“One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically coordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.
In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr. Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.
Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.
What’s next?
Among the recommendations of the authors of the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams with involvement of multidisciplinary teams.
Many centers are already working on models for collaborative care, Dr. Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in “getting stakeholders on the same page, helping them have a shared vision, and working to maximize improvements in outcomes.”
Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr. Hanna said. In the case of the community-powered advocacy organization Critical Mass, they succeeded in getting lawmakers to introduce a bill in the U.S. House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.
Bacteremic sepsis in ALL linked to later cognitive issues
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.
Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.
Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.
Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.
Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.
Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.
“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.
The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.
Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.
As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.
Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.
Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.
This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.
Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.
Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.
The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: ALL survivors with a sepsis history performed worse than did those with no sepsis history on evaluations of spatial planning (difference, 0.78), verbal fluency (0.38), and attention (0.63).
Study details: Prospective cohort study of 212 ALL survivors who underwent neurocognitive testing at a median of nearly 8 years after diagnosis.
Disclosures: The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.
Source: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.
Ketamine infusions may be helpful in central sensitization pain syndromes
LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
EXPERT ANALYSIS FROM PAINWEEK 2018