SAN DIEGO – In patients with heart failure and functional mitral regurgitation, implantation of an investigational device led to reduced MR and improved left ventricular remodeling at 1 year, compared with patients who received sham treatment in the REDUCE-FMR trial.

Jim Kling/MDedge News

The device showed promise in this trial, despite a small sample size, and its nature makes it possible to follow up with other procedures if the disease progresses. “The advantage of this technique is that all other options are still open,” Horst Sievert, MD, director of the CardioVascular Center in Frankfurt, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

The Carillon Mitral Counter System includes two anchors, one in the great cardiac vein and one in the coronary sinus, connected by a shaping ribbon. The tension of the ribbon bolsters the mitral annulus, which in turn reduces mitral regurgitation.

REDUCE-FMR recruited 120 patients from centers in eight countries and randomized 87 to the Carillon device (73 implanted) and 33 to a sham procedure. Sham patients were sedated and received a coronary sinus angiogram. Patients were included if they had dilated ischemic or nonischemic cardiomyopathy and moderate to severe functional MR, among other requirements. Exclusion criteria included existing coronary artery stents in the implant target zone, severe mitral annular calcification, and significant organic mitral valve pathology.

The primary endpoint was the mean reduction of regurgitant volume at 1 year. The treated patients had a 22% reduction of 7.1 mL, while the sham group on average had an 8% increase of 3.3 mL (P = .03). In the as-treated subpopulation, which comprised 45 patients in the treatment group and 13 controls, the values were –7.5 mL and +3.3 mL (P = .02). A per-protocol analysis, which excluded patients who did not meet protocol criteria, led to an amplification of the effect when the study design was adhered to (–12.5 mL vs. +1.3 mL), though this result did not achieve statistical significance owing to the small sample size.

For the safety endpoints, the researchers examined the frequency of major adverse events (MAE), including death, myocardial infarction, cardiac perforation, device embolism, and surgery or percutaneous coronary intervention related to the device at 1 year. In the treatment group, 16.1% experienced a MAE, compared with 18.2% of control patients, a statistically nonsignificant difference.

A secondary efficacy endpoint of change in left ventricular end-diastolic volume showed improvements in the treatment group at 6 months (–12.4 mL) and 12 months (–8.6 mL), compared with increases in the sham group at 6 months (+5.4 mL) and 12 months (+6.5 mL). A similar trend occurred in left ventricular end-systolic volume (–7.8 mL and –4.8 mL; +3.4 mL and +6.1 mL, respectively).

The study was conducted in a patient population similar to that of the COAPT trial, which examined implantation of Abbott’s MitraClip. That study, presented here at TCT 2018 and simultaneously published in the New England Journal of Medicine, also examined patients with heart failure and secondary MR.

However, in REDUCE-FMR, many of the patients had milder heart failure than the researchers had expected: 44.8% in the treatment group had NYHA class II, as did 48.5% in the sham group. That surprise may help identify an appropriate patient population. “I think this device may have a nice spot in between medical therapy and MitraClip implantation, because we have, by chance, a patient population with mild heart insufficiency and mild MR,” said Dr. Sievert.

The two devices also showed different physiologic effects, Michael Mack, MD, said at a press conference. “One subtle difference is that, in this trial, the difference is due to both positive left ventricular remodeling in the treatment arm and continued progression in the sham control. In COAPT, the difference in improvement that we saw was totally due to prevention of progression of disease. We just stabilized the disease to where it was at. So that’s an intriguing difference here, that you actually were able to demonstrate positive left ventricular remodeling,” noted Dr. Mack, medical director for cardiovascular surgery at Baylor Scott & White Medical Center, Plano, Tex. He was a coinvestigator in the COAPT trial.

REDUCE-FMR was funded by Cardiac Dimensions. Dr. Sievert has received consulting fees, travel expenses, and study honoraria from Cardiac Dimensions, and 35 other companies. Dr. Mack has received grant support or had a research contract with Abbott Vascular, Medtronic, and Edwards Lifesciences.

SAN DIEGO – In patients with heart failure and functional mitral regurgitation, implantation of an investigational device led to reduced MR and improved left ventricular remodeling at 1 year, compared with patients who received sham treatment in the REDUCE-FMR trial.

Jim Kling/MDedge News

The device showed promise in this trial, despite a small sample size, and its nature makes it possible to follow up with other procedures if the disease progresses. “The advantage of this technique is that all other options are still open,” Horst Sievert, MD, director of the CardioVascular Center in Frankfurt, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

The Carillon Mitral Counter System includes two anchors, one in the great cardiac vein and one in the coronary sinus, connected by a shaping ribbon. The tension of the ribbon bolsters the mitral annulus, which in turn reduces mitral regurgitation.

REDUCE-FMR recruited 120 patients from centers in eight countries and randomized 87 to the Carillon device (73 implanted) and 33 to a sham procedure. Sham patients were sedated and received a coronary sinus angiogram. Patients were included if they had dilated ischemic or nonischemic cardiomyopathy and moderate to severe functional MR, among other requirements. Exclusion criteria included existing coronary artery stents in the implant target zone, severe mitral annular calcification, and significant organic mitral valve pathology.

The primary endpoint was the mean reduction of regurgitant volume at 1 year. The treated patients had a 22% reduction of 7.1 mL, while the sham group on average had an 8% increase of 3.3 mL (P = .03). In the as-treated subpopulation, which comprised 45 patients in the treatment group and 13 controls, the values were –7.5 mL and +3.3 mL (P = .02). A per-protocol analysis, which excluded patients who did not meet protocol criteria, led to an amplification of the effect when the study design was adhered to (–12.5 mL vs. +1.3 mL), though this result did not achieve statistical significance owing to the small sample size.

For the safety endpoints, the researchers examined the frequency of major adverse events (MAE), including death, myocardial infarction, cardiac perforation, device embolism, and surgery or percutaneous coronary intervention related to the device at 1 year. In the treatment group, 16.1% experienced a MAE, compared with 18.2% of control patients, a statistically nonsignificant difference.

A secondary efficacy endpoint of change in left ventricular end-diastolic volume showed improvements in the treatment group at 6 months (–12.4 mL) and 12 months (–8.6 mL), compared with increases in the sham group at 6 months (+5.4 mL) and 12 months (+6.5 mL). A similar trend occurred in left ventricular end-systolic volume (–7.8 mL and –4.8 mL; +3.4 mL and +6.1 mL, respectively).

The study was conducted in a patient population similar to that of the COAPT trial, which examined implantation of Abbott’s MitraClip. That study, presented here at TCT 2018 and simultaneously published in the New England Journal of Medicine, also examined patients with heart failure and secondary MR.

However, in REDUCE-FMR, many of the patients had milder heart failure than the researchers had expected: 44.8% in the treatment group had NYHA class II, as did 48.5% in the sham group. That surprise may help identify an appropriate patient population. “I think this device may have a nice spot in between medical therapy and MitraClip implantation, because we have, by chance, a patient population with mild heart insufficiency and mild MR,” said Dr. Sievert.

The two devices also showed different physiologic effects, Michael Mack, MD, said at a press conference. “One subtle difference is that, in this trial, the difference is due to both positive left ventricular remodeling in the treatment arm and continued progression in the sham control. In COAPT, the difference in improvement that we saw was totally due to prevention of progression of disease. We just stabilized the disease to where it was at. So that’s an intriguing difference here, that you actually were able to demonstrate positive left ventricular remodeling,” noted Dr. Mack, medical director for cardiovascular surgery at Baylor Scott & White Medical Center, Plano, Tex. He was a coinvestigator in the COAPT trial.

REDUCE-FMR was funded by Cardiac Dimensions. Dr. Sievert has received consulting fees, travel expenses, and study honoraria from Cardiac Dimensions, and 35 other companies. Dr. Mack has received grant support or had a research contract with Abbott Vascular, Medtronic, and Edwards Lifesciences.

SAN DIEGO – In patients with heart failure and functional mitral regurgitation, implantation of an investigational device led to reduced MR and improved left ventricular remodeling at 1 year, compared with patients who received sham treatment in the REDUCE-FMR trial.

Jim Kling/MDedge News

The device showed promise in this trial, despite a small sample size, and its nature makes it possible to follow up with other procedures if the disease progresses. “The advantage of this technique is that all other options are still open,” Horst Sievert, MD, director of the CardioVascular Center in Frankfurt, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.

The Carillon Mitral Counter System includes two anchors, one in the great cardiac vein and one in the coronary sinus, connected by a shaping ribbon. The tension of the ribbon bolsters the mitral annulus, which in turn reduces mitral regurgitation.

REDUCE-FMR recruited 120 patients from centers in eight countries and randomized 87 to the Carillon device (73 implanted) and 33 to a sham procedure. Sham patients were sedated and received a coronary sinus angiogram. Patients were included if they had dilated ischemic or nonischemic cardiomyopathy and moderate to severe functional MR, among other requirements. Exclusion criteria included existing coronary artery stents in the implant target zone, severe mitral annular calcification, and significant organic mitral valve pathology.

The primary endpoint was the mean reduction of regurgitant volume at 1 year. The treated patients had a 22% reduction of 7.1 mL, while the sham group on average had an 8% increase of 3.3 mL (P = .03). In the as-treated subpopulation, which comprised 45 patients in the treatment group and 13 controls, the values were –7.5 mL and +3.3 mL (P = .02). A per-protocol analysis, which excluded patients who did not meet protocol criteria, led to an amplification of the effect when the study design was adhered to (–12.5 mL vs. +1.3 mL), though this result did not achieve statistical significance owing to the small sample size.

For the safety endpoints, the researchers examined the frequency of major adverse events (MAE), including death, myocardial infarction, cardiac perforation, device embolism, and surgery or percutaneous coronary intervention related to the device at 1 year. In the treatment group, 16.1% experienced a MAE, compared with 18.2% of control patients, a statistically nonsignificant difference.

A secondary efficacy endpoint of change in left ventricular end-diastolic volume showed improvements in the treatment group at 6 months (–12.4 mL) and 12 months (–8.6 mL), compared with increases in the sham group at 6 months (+5.4 mL) and 12 months (+6.5 mL). A similar trend occurred in left ventricular end-systolic volume (–7.8 mL and –4.8 mL; +3.4 mL and +6.1 mL, respectively).

The study was conducted in a patient population similar to that of the COAPT trial, which examined implantation of Abbott’s MitraClip. That study, presented here at TCT 2018 and simultaneously published in the New England Journal of Medicine, also examined patients with heart failure and secondary MR.

However, in REDUCE-FMR, many of the patients had milder heart failure than the researchers had expected: 44.8% in the treatment group had NYHA class II, as did 48.5% in the sham group. That surprise may help identify an appropriate patient population. “I think this device may have a nice spot in between medical therapy and MitraClip implantation, because we have, by chance, a patient population with mild heart insufficiency and mild MR,” said Dr. Sievert.

The two devices also showed different physiologic effects, Michael Mack, MD, said at a press conference. “One subtle difference is that, in this trial, the difference is due to both positive left ventricular remodeling in the treatment arm and continued progression in the sham control. In COAPT, the difference in improvement that we saw was totally due to prevention of progression of disease. We just stabilized the disease to where it was at. So that’s an intriguing difference here, that you actually were able to demonstrate positive left ventricular remodeling,” noted Dr. Mack, medical director for cardiovascular surgery at Baylor Scott & White Medical Center, Plano, Tex. He was a coinvestigator in the COAPT trial.

REDUCE-FMR was funded by Cardiac Dimensions. Dr. Sievert has received consulting fees, travel expenses, and study honoraria from Cardiac Dimensions, and 35 other companies. Dr. Mack has received grant support or had a research contract with Abbott Vascular, Medtronic, and Edwards Lifesciences.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.

TORONTO – Comprehensive genetic profiling (CGP) helps identify targeted therapies for patients with cancer and facilitates clinical trial enrollment, according to findings from a retrospective study of 46 patients who were followed for 3 years after CGP.

A total of 263 genomic alterations were identified in the patients, leading to a change of therapy in 26% of cases and referral to a clinical trial in 13%, Kimberly Rohan, APN, reported at the World Conference on Lung Cancer.

The 13% referral rate was surprising, “because that’s way above the national average for enrollment in a clinical trial,” Ms. Rohan, of the Edward Cancer Center in Naperville, Ill., said during a press briefing at the meeting, sponsored by the International Association for the Study of Lung Cancer.

“Among those diagnosed with lung cancer, 6% were referred to clinical trials and 34% had a change of therapy,” she said, noting that all but one of the patients had non–small cell lung cancer, and the other had small cell lung cancer and many alterations.

Of note, three patients enrolled in hospice care based on the findings; sometimes, palliative care is the most appropriate option, and this information helps patients and their families make those decisions, Ms. Rohan said.

Patients were tested between 2014 and 2017, and the review looked at the number of genomic alterations identified in each, what treatments were associated with potential clinical trial benefits, what therapies were associated with lack of response, and the effects of the CGP findings on decision making.

An important next step is to work with payors to get them to pay for CGP testing, she said. “These tests are expensive so a lot of [insurance companies] don’t want to pay for them, but this data will help support the fact that [these tests] do allow better treatments for patients and allow patients to make better decisions for themselves in regard to treatment.”

Ms. Rohan is a speaker or advisory board member for Merck, Genentech, and AstraZeneca.

The hematopoietic action of the thrombopoietin receptor (TPO-R) agonist eltrombopag (Promacta) occurs at the stem cell level through its effects on iron chelation that in turn leads to hematopoietic stem cell (HSC) stimulation and self-renewal, investigators report.

Studying the effects of eltrombopag treatment in mouse models and in bone marrow cells isolated from patients, Britta Will, PhD, from the Albert Einstein College of Medicine, New York, and her colleagues found that eltrombopag’s stimulatory effects on stem cell self-renewal were independent of the thrombopoietin receptor.

“The iron chelation–dependent mechanism of [eltrombopag] is very likely to confer clinical relevance in the context of enhancing TPO-R–dependent HSC stimulation and reinforcing stem cell identity through wide-ranging iron-dependent metabolic reprogramming, which increases healthy stem cells without causing their exhaustion in bone marrow failure syndromes, as well as aid in preserving functional HSCs under cellular stress (such as transplantation, cytotoxic treatment, or irradiation),” they wrote in Science Translational Medicine.

To gain insight into the effects of eltrombopag on the earliest stages of hematopoiesis, the investigators conducted a series of experiments, starting with an assessment of the effects of the agent on the functional hallmarks of primary human stem cells.

Using assays for differentiation, self-renewal, and cell proliferation in human bone marrow cell lines, they found that eltrombopag acts directly on multilineage hematopoiesis by fostering commitment to differentiation at the multipotent progenitor (MPP) cell level and by enhancing self-renewal of hematopoietic stem cells.

Next, they investigated whether eltrombopag promoted hematopoiesis by activating the TPO-R, or through a different mechanism, and found that its action was independent of the thrombopoietin receptor. Specifically, they found that eltrombopag “elicits gene expression alterations in HSCs consistent with a molecular response to reduced intracellular iron content, consisting of decreased glycolysis and enhanced lipid and protein catabolic pathway activation.”

To show that the effect was independent of TPO-R, they then turned to mouse models (eltrombopag is known to activate TPO-R signaling in primate cells, including in humans, but cannot do so in mice, they explained). They showed that in mice, eltrombopag is capable of stimulating HSCs even in the absence of action on the TPO-R.

They also demonstrated that HSCs from both humans and mice have evidence of changes in metabolism and in gene expression that were consistent with reduction of labile iron pools that stem cells rely on for maintenance. When they preloaded cells with iron, the stimulatory effects of eltrombopag were negated, further supporting the iron-chelating effects of the drug on HSC stimulation.

Finally, they looked at HSC function in bone marrow mononuclear cells from patients with immune thrombocytopenia who were being treated with eltrombopag and found a threefold greater increase in the number of functional HSCs, compared with samples from patients treated with the TPO-R agonist romiplostim (Nplate), which does not have iron-chelating properties.

“Together, our data demonstrate a TPO-R–independent stem cell stimulatory function of EP and suggest that free intracellular iron pools may serve as a rheostat for HSC maintenance,” the investigators wrote.

The study was supported by the New York State Department of Health. Dr. Will and two coauthors reported research support from GlaxoSmithKline and Novartis, and serving as consultants for Novartis. Two of the co-authors are employees of Novartis.

SOURCE: Kao YR et al. Sci Transl Med. 2018 Sep 12;10(458). doi: 10.1126/scitranslmed.aas9563.
 

The hematopoietic action of the thrombopoietin receptor (TPO-R) agonist eltrombopag (Promacta) occurs at the stem cell level through its effects on iron chelation that in turn leads to hematopoietic stem cell (HSC) stimulation and self-renewal, investigators report.

Studying the effects of eltrombopag treatment in mouse models and in bone marrow cells isolated from patients, Britta Will, PhD, from the Albert Einstein College of Medicine, New York, and her colleagues found that eltrombopag’s stimulatory effects on stem cell self-renewal were independent of the thrombopoietin receptor.

“The iron chelation–dependent mechanism of [eltrombopag] is very likely to confer clinical relevance in the context of enhancing TPO-R–dependent HSC stimulation and reinforcing stem cell identity through wide-ranging iron-dependent metabolic reprogramming, which increases healthy stem cells without causing their exhaustion in bone marrow failure syndromes, as well as aid in preserving functional HSCs under cellular stress (such as transplantation, cytotoxic treatment, or irradiation),” they wrote in Science Translational Medicine.

To gain insight into the effects of eltrombopag on the earliest stages of hematopoiesis, the investigators conducted a series of experiments, starting with an assessment of the effects of the agent on the functional hallmarks of primary human stem cells.

Using assays for differentiation, self-renewal, and cell proliferation in human bone marrow cell lines, they found that eltrombopag acts directly on multilineage hematopoiesis by fostering commitment to differentiation at the multipotent progenitor (MPP) cell level and by enhancing self-renewal of hematopoietic stem cells.

Next, they investigated whether eltrombopag promoted hematopoiesis by activating the TPO-R, or through a different mechanism, and found that its action was independent of the thrombopoietin receptor. Specifically, they found that eltrombopag “elicits gene expression alterations in HSCs consistent with a molecular response to reduced intracellular iron content, consisting of decreased glycolysis and enhanced lipid and protein catabolic pathway activation.”

To show that the effect was independent of TPO-R, they then turned to mouse models (eltrombopag is known to activate TPO-R signaling in primate cells, including in humans, but cannot do so in mice, they explained). They showed that in mice, eltrombopag is capable of stimulating HSCs even in the absence of action on the TPO-R.

They also demonstrated that HSCs from both humans and mice have evidence of changes in metabolism and in gene expression that were consistent with reduction of labile iron pools that stem cells rely on for maintenance. When they preloaded cells with iron, the stimulatory effects of eltrombopag were negated, further supporting the iron-chelating effects of the drug on HSC stimulation.

Finally, they looked at HSC function in bone marrow mononuclear cells from patients with immune thrombocytopenia who were being treated with eltrombopag and found a threefold greater increase in the number of functional HSCs, compared with samples from patients treated with the TPO-R agonist romiplostim (Nplate), which does not have iron-chelating properties.

“Together, our data demonstrate a TPO-R–independent stem cell stimulatory function of EP and suggest that free intracellular iron pools may serve as a rheostat for HSC maintenance,” the investigators wrote.

The study was supported by the New York State Department of Health. Dr. Will and two coauthors reported research support from GlaxoSmithKline and Novartis, and serving as consultants for Novartis. Two of the co-authors are employees of Novartis.

SOURCE: Kao YR et al. Sci Transl Med. 2018 Sep 12;10(458). doi: 10.1126/scitranslmed.aas9563.
 

The hematopoietic action of the thrombopoietin receptor (TPO-R) agonist eltrombopag (Promacta) occurs at the stem cell level through its effects on iron chelation that in turn leads to hematopoietic stem cell (HSC) stimulation and self-renewal, investigators report.

Studying the effects of eltrombopag treatment in mouse models and in bone marrow cells isolated from patients, Britta Will, PhD, from the Albert Einstein College of Medicine, New York, and her colleagues found that eltrombopag’s stimulatory effects on stem cell self-renewal were independent of the thrombopoietin receptor.

“The iron chelation–dependent mechanism of [eltrombopag] is very likely to confer clinical relevance in the context of enhancing TPO-R–dependent HSC stimulation and reinforcing stem cell identity through wide-ranging iron-dependent metabolic reprogramming, which increases healthy stem cells without causing their exhaustion in bone marrow failure syndromes, as well as aid in preserving functional HSCs under cellular stress (such as transplantation, cytotoxic treatment, or irradiation),” they wrote in Science Translational Medicine.

To gain insight into the effects of eltrombopag on the earliest stages of hematopoiesis, the investigators conducted a series of experiments, starting with an assessment of the effects of the agent on the functional hallmarks of primary human stem cells.

Using assays for differentiation, self-renewal, and cell proliferation in human bone marrow cell lines, they found that eltrombopag acts directly on multilineage hematopoiesis by fostering commitment to differentiation at the multipotent progenitor (MPP) cell level and by enhancing self-renewal of hematopoietic stem cells.

Next, they investigated whether eltrombopag promoted hematopoiesis by activating the TPO-R, or through a different mechanism, and found that its action was independent of the thrombopoietin receptor. Specifically, they found that eltrombopag “elicits gene expression alterations in HSCs consistent with a molecular response to reduced intracellular iron content, consisting of decreased glycolysis and enhanced lipid and protein catabolic pathway activation.”

To show that the effect was independent of TPO-R, they then turned to mouse models (eltrombopag is known to activate TPO-R signaling in primate cells, including in humans, but cannot do so in mice, they explained). They showed that in mice, eltrombopag is capable of stimulating HSCs even in the absence of action on the TPO-R.

They also demonstrated that HSCs from both humans and mice have evidence of changes in metabolism and in gene expression that were consistent with reduction of labile iron pools that stem cells rely on for maintenance. When they preloaded cells with iron, the stimulatory effects of eltrombopag were negated, further supporting the iron-chelating effects of the drug on HSC stimulation.

Finally, they looked at HSC function in bone marrow mononuclear cells from patients with immune thrombocytopenia who were being treated with eltrombopag and found a threefold greater increase in the number of functional HSCs, compared with samples from patients treated with the TPO-R agonist romiplostim (Nplate), which does not have iron-chelating properties.

“Together, our data demonstrate a TPO-R–independent stem cell stimulatory function of EP and suggest that free intracellular iron pools may serve as a rheostat for HSC maintenance,” the investigators wrote.

The study was supported by the New York State Department of Health. Dr. Will and two coauthors reported research support from GlaxoSmithKline and Novartis, and serving as consultants for Novartis. Two of the co-authors are employees of Novartis.

SOURCE: Kao YR et al. Sci Transl Med. 2018 Sep 12;10(458). doi: 10.1126/scitranslmed.aas9563.
 

The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Courtesy Novartis

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.

In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, in draft guidance issued Sept. 19, NICE recommended against using tisagenlecleucel for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

jensmith@mdedge.com

The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Courtesy Novartis

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.

In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, in draft guidance issued Sept. 19, NICE recommended against using tisagenlecleucel for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

jensmith@mdedge.com

The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Courtesy Novartis

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.

In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, in draft guidance issued Sept. 19, NICE recommended against using tisagenlecleucel for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

jensmith@mdedge.com

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.

aotto@mdedge.com

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.

aotto@mdedge.com

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.

aotto@mdedge.com

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.

jensmith@mdedge.com

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.

jensmith@mdedge.com

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.

jensmith@mdedge.com

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.

javi_indy/ Thinkstock

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.

javi_indy/ Thinkstock

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.

javi_indy/ Thinkstock

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 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.

Antonio_Diaz/Thinkstock

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.

Antonio_Diaz/Thinkstock

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.

Antonio_Diaz/Thinkstock

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).

SAN DIEGO – Hair removal has been ranked as the most commonly litigated procedure in laser surgery, although fewer procedures for hair removal are performed 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.

dbrunk@mdedge.com



 

SAN DIEGO – Hair removal has been ranked as the most commonly litigated procedure in laser surgery, although fewer procedures for hair removal are performed 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.

dbrunk@mdedge.com



 

SAN DIEGO – Hair removal has been ranked as the most commonly litigated procedure in laser surgery, although fewer procedures for hair removal are performed 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.

dbrunk@mdedge.com



 

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.

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.