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Top AGA Community patient cases
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Adherence to noninvasive CRC screening (http://ow.ly/6eng30qfUKq)
2. Q&A with Guideline authors: Management of gastric intestinal metaplasia (GIM) (http://ow.ly/Cxsl30qfUYm).
3. IBD patient: Crohn’s colitis (http://ow.ly/DsOg30qfUNt).
4. Patient with intractable abdominal pain (http://ow.ly/EPFi30qfUsi).
5. IBD patient: Ulcerative colitis (http://ow.ly/d6e730qfUVZ).
Access these clinical cases and more discussions at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Adherence to noninvasive CRC screening (http://ow.ly/6eng30qfUKq)
2. Q&A with Guideline authors: Management of gastric intestinal metaplasia (GIM) (http://ow.ly/Cxsl30qfUYm).
3. IBD patient: Crohn’s colitis (http://ow.ly/DsOg30qfUNt).
4. Patient with intractable abdominal pain (http://ow.ly/EPFi30qfUsi).
5. IBD patient: Ulcerative colitis (http://ow.ly/d6e730qfUVZ).
Access these clinical cases and more discussions at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Adherence to noninvasive CRC screening (http://ow.ly/6eng30qfUKq)
2. Q&A with Guideline authors: Management of gastric intestinal metaplasia (GIM) (http://ow.ly/Cxsl30qfUYm).
3. IBD patient: Crohn’s colitis (http://ow.ly/DsOg30qfUNt).
4. Patient with intractable abdominal pain (http://ow.ly/EPFi30qfUsi).
5. IBD patient: Ulcerative colitis (http://ow.ly/d6e730qfUVZ).
Access these clinical cases and more discussions at https://community.gastro.org/discussions.
Specific markers detect psoriatic disease inflammation without elevated CRP
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
according to a cross-sectional study of patients and healthy controls.
“Different clinical subsets of psoriatic disease based on skin, entheseal, and joint involvement are characterized by specific inflammation marker profiles,” Maria V. Sokolova, MD, of Friedrich-Alexander University Erlangen-Nuremberg and University Clinic Erlangen (Germany) and colleagues reported in Arthritis Research & Therapy. “Treatment of psoriatic disease with cytokine inhibitors reduces these elevated levels of systemic inflammation markers.”
Quantifying systemic inflammation in psoriatic disease has been a challenge, Dr. Sokolova and colleagues wrote. Levels of C-reactive protein (CRP), a commonly used measure of systemic inflammation, “are often low or absent.” To examine other potential markers of systemic inflammation in psoriatic disease, the investigators conducted cross-sectional and longitudinal studies that included healthy controls and patients with psoriatic disease. Patients had isolated or combined manifestations of psoriatic disease, including the skin, the entheses, and the joints. The researchers grouped patients by isolated psoriatic skin disease; isolated enthesitis; isolated arthritis; psoriatic skin disease with enthesitis; psoriatic skin disease with arthritis; arthritis and enthesitis; and combined psoriatic skin disease, arthritis, and enthesitis.
Data from more than 100 patients
The researchers first assessed 10 potential markers using enzyme-linked immunosorbent assay: calprotectin, interleukin-22, IL-8, lipocalin 2, beta-defensin 2, IL-17, IL-23, vascular endothelial growth factors, LL37 (cathelicidin), and pentraxin 3. They measured the markers in 10 healthy controls and 10 patients with active polymorphic psoriatic arthritis. Five parameters – beta-defensin 2, lipocalin 2, IL-22, IL-8, and calprotectin – significantly differed between healthy controls and patients with psoriatic disease. Lipocalin 2, beta-defensin 2, and IL-22 are associated with IL-17/IL-23 activation, and calprotectin and IL-8 are associated with innate immune cell activation. The other markers did not significantly differ or were not detectable in enough participants.
To validate the signals, the researchers measured the five parameters as well as CRP in 105 controls and 105 patients with psoriatic disease, including 15 patients in each of the seven disease pattern groups. “As expected, CRP levels were normal in the majority of individuals,” the authors wrote. The proportion of patients with CRP greater than 5 mg/L was 0% in isolated psoriatic skin disease, 0% in isolated enthesitis; 20% in isolated arthritis; 7% in psoriatic skin disease with enthesitis; 33% in psoriatic skin disease with arthritis; 27% in arthritis with enthesitis; and 33% in combined psoriatic skin disease, arthritis, and enthesitis.
“Only a subset of patients with arthritis, but not patients with skin or entheseal disease show elevated CRP,” the researchers wrote. “In sharp contrast,” beta-defensin 2 and lipocalin 2 were elevated in a majority of patients with monomorphic skin and entheseal disease, but not in joint disease. “Both proteins were significantly correlated to the extent of skin disease and to a lesser extent also entheseal disease,” they added. Calprotectin and IL-8 were elevated in a majority of patients with joint disease and correlated with the extent of arthritis. “IL-22 was elevated ... in all three manifestations of psoriatic disease,” and the vast majority of patients with polymorphic disease had “widespread marker elevation,” the researchers wrote.
Effects of treatment
In a study of 20 patients with psoriatic arthritis, treatment with secukinumab or adalimumab significantly lowered all five markers. Compared with tumor necrosis factor inhibition with adalimumab, “IL-17 inhibition [with secukinumab] showed a more pronounced lowering of lipocalin 2 and beta-defensin 2 levels,” the investigators noted.
“These results confirm earlier data showing elevated beta-defensin levels in psoriasis patients and its association with the extent of skin involvement,” Dr. Sokolova and colleagues wrote. “Overall, these results offer a new possibility to measure systemic inflammation in psoriatic disease.”
The study was supported by the German Research Foundation and other grant and fellowship funding. The authors had no competing interests.
SOURCE: Sokolova MV et al. Arthritis Res Ther. 2020;22:26.
FROM ARTHRITIS RESEARCH & THERAPY
Pondering jumping into teledermatology?
LAHAINA, HAWAII – Teledermatology and dermoscopy were made for each other, Trilokraj Tejasvi, MBBS, MD, declared at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
“If somebody is The dermatoscope manufacturers make teledermoscopy systems with attachments for iPhones, iPads, and Android devices,” said Dr. Tejasvi, who is director of teledermatology services and also director of the cutaneous lymphoma program at the University of Michigan, Ann Arbor.
To make his point, he presented slides of six standard unenhanced teledermatologic photos of ambiguous pigmented skin lesions. When he asked the large audience which ones they’d want to biopsy and which they were confident were benign, there was absolutely no consensus. But when he followed up with teledermoscopic photos of the same lesions, the dermoscopists in the audience quickly voiced agreement that four of the lesions were benign and two were obvious melanoma. Based on that information, instead of having to bring in all six patients for biopsy of their indeterminant suspicious lesions, only two of the patients would need to come in promptly for treatment of their malignancy.
“Dermoscopy changes the whole triage system and the teledermoscopy concept model, because dermoscopy remains the same: it’s going to stay [two-dimensional] whether you’re going to see the images in the clinic or in teledermatology. So using teledermoscopy images actually makes it far better for your teledermatology services,” explained Dr. Tejasvi, who is also chief of the dermatology service at the Ann Arbor Veterans Affairs Hospital.
Why get into teledermatology?
The benefits of teledermatology include earlier diagnosis and treatment of skin cancers as documented in a Spanish study of 43,677 patients. The Spanish dermatologists reported that teledermatologically detected melanomas had a thinner Breslow depth and lower tumor stage because they were diagnosed earlier. Teledermatology also brought a twofold increase in the basal cell carcinoma detection rate and – most importantly – a reduction in time to biopsy for what turned out to be skin cancers (JAMA Dermatol. 2015 Dec 1;151[12]:1289-90).
In addition, teledermatology is an effective triage tool for busy clinicians whose appointment calendars are booked weeks or months in advance.
“Let’s say you are the only dermatologist in the surrounding five counties. You can use teledermatology to see which patients actually need to come to your clinic,” Dr. Tejasvri said. Just make sure the referring primary care providers know to send photos taken with the dermatoscope attachment.
Internet-based teledermatology also provides a way to follow patients with chronic conditions, including psoriasis, atopic dermatitis, and venous ulcers, he noted.
Before getting started
Dr. Tejasvri emphasized the importance of visiting the American Academy of Dermatology Teledermatology Task Force website as well as the American Telemedicine Association’s Teledermatology Special Interest Group, which he chairs. These resources, he stressed, are invaluable.
The AAD site, open to all academy members, includes a tool kit for getting started in teledermatology. It’s individually tailored for the dermatologist in solo, small group, academic, or multispecialty practice. This highly practical tool kit includes a checklist that aids in determining whether a dermatologist’s practice is suited for teledermatology, as well as the suggested optimal teledermatology practice model for that individual, the nuts and bolts of equipment, relevant state laws, and how to navigate legal concerns, among the most critical of which is to get in writing the malpractice insurer’s verbal reassurance that the policy covers telemedicine.
The American Telemedicine Association Teledermatology Special Interest Group provides best-practice guidelines (Telemed J E Health. 2016 Dec;22[12]:981-90)
Teledermatology practice model options
The most common teledermatology model is called “store-and-forward.” It relies upon transmission of still images of skin lesions. Its advantages are that it’s not dependent upon internet speed and it accommodates physicians working in different time zones. Most commonly, this is a consult model in which a remote primary care provider takes the photos and transmits them to the dermatologist specialist. The referring provider retains responsibility for patient care.
The other model entails creation of a virtual clinic with real-time videoconference-based communication using a HIPAA-compliant high-speed broadband internet connection. The advantages are that reimbursement is good – indeed, the same as for a face-to-face office visit – and it’s possible to ask questions of the patient and referring physician, although that’s generally not necessary for the straightforward evaluation of suspicious pigmented or nonpigmented skin lesions. However, the video image quality isn’t as good as with still photos, the virtual clinic requires dedicated scheduling, and the quality of the experience is highly dependent upon internet speed.
“If you have a bad internet speed the whole process becomes choppy. When you ask a question, the answer you get is the one to your previous question,” Dr. Tejasvi said.
Reimbursement
Currently 38 states and Washington, D.C., have laws governing private payer telehealth reimbursement policy.
Under the 2019 Medicare physician fee schedule, code number 99446 – interprofessional telephone/internet consult lasting 5-10 minutes – pays $18.36. A 99447, lasting 11-20 minutes, pays $36.36, and a 99448, representing a 21-30 minute interprofessional consult, pays $54.72.
“Reimbursement is poor. It’s not a lot at all. If you spend 5-10 minutes on a consult you get paid about 20 bucks. But it’s better than nothing, and it used to be that patients had to pay out of pocket,” the dermatologist commented.
And of course, the improved timely and efficient patient access to dermatologist evaluation of potential skin cancer that’s afforded via teledermatology helps out with the profession’s workforce shortage and responds to the common criticism that dermatologists are geographically maldistributed and treatment delayed is treatment denied.
How accurate is teledermatology?
Numerous studies have reported diagnostic concordance rates between teledermatology and face-to-face clinical diagnosis of 72.5%-90% for melanoma, dropping off markedly to 31.2%-62% for lentigines. However, teledermoscopic images greatly improved the diagnostic accuracy.
In one recent study involving teledermatology versus face-to-face evaluation of 293 index lesions, the face-to-face dermatologist examination turned up 131 incidental skin lesions, including 6 incidental melanomas not suspected or photographed by the consulting primary care providers. That worked out to a 2.6% risk of incidental melanoma per consult, which Dr. Tejasvi called “kind of scary.”
“All six of the incidental melanomas were located on the back, chest, or abdomen, so a good teaching point is that, if you’re doing a teledermatology consult, ask the primary care provider who’s sending you this consult to do a careful waist-up exam to look for other lesions,” he advised.
He added that more and larger studies are needed in order to determine the diagnostic concordance rate for nonpigmented lesions.
Dr. Tejasvi reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Teledermatology and dermoscopy were made for each other, Trilokraj Tejasvi, MBBS, MD, declared at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
“If somebody is The dermatoscope manufacturers make teledermoscopy systems with attachments for iPhones, iPads, and Android devices,” said Dr. Tejasvi, who is director of teledermatology services and also director of the cutaneous lymphoma program at the University of Michigan, Ann Arbor.
To make his point, he presented slides of six standard unenhanced teledermatologic photos of ambiguous pigmented skin lesions. When he asked the large audience which ones they’d want to biopsy and which they were confident were benign, there was absolutely no consensus. But when he followed up with teledermoscopic photos of the same lesions, the dermoscopists in the audience quickly voiced agreement that four of the lesions were benign and two were obvious melanoma. Based on that information, instead of having to bring in all six patients for biopsy of their indeterminant suspicious lesions, only two of the patients would need to come in promptly for treatment of their malignancy.
“Dermoscopy changes the whole triage system and the teledermoscopy concept model, because dermoscopy remains the same: it’s going to stay [two-dimensional] whether you’re going to see the images in the clinic or in teledermatology. So using teledermoscopy images actually makes it far better for your teledermatology services,” explained Dr. Tejasvi, who is also chief of the dermatology service at the Ann Arbor Veterans Affairs Hospital.
Why get into teledermatology?
The benefits of teledermatology include earlier diagnosis and treatment of skin cancers as documented in a Spanish study of 43,677 patients. The Spanish dermatologists reported that teledermatologically detected melanomas had a thinner Breslow depth and lower tumor stage because they were diagnosed earlier. Teledermatology also brought a twofold increase in the basal cell carcinoma detection rate and – most importantly – a reduction in time to biopsy for what turned out to be skin cancers (JAMA Dermatol. 2015 Dec 1;151[12]:1289-90).
In addition, teledermatology is an effective triage tool for busy clinicians whose appointment calendars are booked weeks or months in advance.
“Let’s say you are the only dermatologist in the surrounding five counties. You can use teledermatology to see which patients actually need to come to your clinic,” Dr. Tejasvri said. Just make sure the referring primary care providers know to send photos taken with the dermatoscope attachment.
Internet-based teledermatology also provides a way to follow patients with chronic conditions, including psoriasis, atopic dermatitis, and venous ulcers, he noted.
Before getting started
Dr. Tejasvri emphasized the importance of visiting the American Academy of Dermatology Teledermatology Task Force website as well as the American Telemedicine Association’s Teledermatology Special Interest Group, which he chairs. These resources, he stressed, are invaluable.
The AAD site, open to all academy members, includes a tool kit for getting started in teledermatology. It’s individually tailored for the dermatologist in solo, small group, academic, or multispecialty practice. This highly practical tool kit includes a checklist that aids in determining whether a dermatologist’s practice is suited for teledermatology, as well as the suggested optimal teledermatology practice model for that individual, the nuts and bolts of equipment, relevant state laws, and how to navigate legal concerns, among the most critical of which is to get in writing the malpractice insurer’s verbal reassurance that the policy covers telemedicine.
The American Telemedicine Association Teledermatology Special Interest Group provides best-practice guidelines (Telemed J E Health. 2016 Dec;22[12]:981-90)
Teledermatology practice model options
The most common teledermatology model is called “store-and-forward.” It relies upon transmission of still images of skin lesions. Its advantages are that it’s not dependent upon internet speed and it accommodates physicians working in different time zones. Most commonly, this is a consult model in which a remote primary care provider takes the photos and transmits them to the dermatologist specialist. The referring provider retains responsibility for patient care.
The other model entails creation of a virtual clinic with real-time videoconference-based communication using a HIPAA-compliant high-speed broadband internet connection. The advantages are that reimbursement is good – indeed, the same as for a face-to-face office visit – and it’s possible to ask questions of the patient and referring physician, although that’s generally not necessary for the straightforward evaluation of suspicious pigmented or nonpigmented skin lesions. However, the video image quality isn’t as good as with still photos, the virtual clinic requires dedicated scheduling, and the quality of the experience is highly dependent upon internet speed.
“If you have a bad internet speed the whole process becomes choppy. When you ask a question, the answer you get is the one to your previous question,” Dr. Tejasvi said.
Reimbursement
Currently 38 states and Washington, D.C., have laws governing private payer telehealth reimbursement policy.
Under the 2019 Medicare physician fee schedule, code number 99446 – interprofessional telephone/internet consult lasting 5-10 minutes – pays $18.36. A 99447, lasting 11-20 minutes, pays $36.36, and a 99448, representing a 21-30 minute interprofessional consult, pays $54.72.
“Reimbursement is poor. It’s not a lot at all. If you spend 5-10 minutes on a consult you get paid about 20 bucks. But it’s better than nothing, and it used to be that patients had to pay out of pocket,” the dermatologist commented.
And of course, the improved timely and efficient patient access to dermatologist evaluation of potential skin cancer that’s afforded via teledermatology helps out with the profession’s workforce shortage and responds to the common criticism that dermatologists are geographically maldistributed and treatment delayed is treatment denied.
How accurate is teledermatology?
Numerous studies have reported diagnostic concordance rates between teledermatology and face-to-face clinical diagnosis of 72.5%-90% for melanoma, dropping off markedly to 31.2%-62% for lentigines. However, teledermoscopic images greatly improved the diagnostic accuracy.
In one recent study involving teledermatology versus face-to-face evaluation of 293 index lesions, the face-to-face dermatologist examination turned up 131 incidental skin lesions, including 6 incidental melanomas not suspected or photographed by the consulting primary care providers. That worked out to a 2.6% risk of incidental melanoma per consult, which Dr. Tejasvi called “kind of scary.”
“All six of the incidental melanomas were located on the back, chest, or abdomen, so a good teaching point is that, if you’re doing a teledermatology consult, ask the primary care provider who’s sending you this consult to do a careful waist-up exam to look for other lesions,” he advised.
He added that more and larger studies are needed in order to determine the diagnostic concordance rate for nonpigmented lesions.
Dr. Tejasvi reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Teledermatology and dermoscopy were made for each other, Trilokraj Tejasvi, MBBS, MD, declared at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
“If somebody is The dermatoscope manufacturers make teledermoscopy systems with attachments for iPhones, iPads, and Android devices,” said Dr. Tejasvi, who is director of teledermatology services and also director of the cutaneous lymphoma program at the University of Michigan, Ann Arbor.
To make his point, he presented slides of six standard unenhanced teledermatologic photos of ambiguous pigmented skin lesions. When he asked the large audience which ones they’d want to biopsy and which they were confident were benign, there was absolutely no consensus. But when he followed up with teledermoscopic photos of the same lesions, the dermoscopists in the audience quickly voiced agreement that four of the lesions were benign and two were obvious melanoma. Based on that information, instead of having to bring in all six patients for biopsy of their indeterminant suspicious lesions, only two of the patients would need to come in promptly for treatment of their malignancy.
“Dermoscopy changes the whole triage system and the teledermoscopy concept model, because dermoscopy remains the same: it’s going to stay [two-dimensional] whether you’re going to see the images in the clinic or in teledermatology. So using teledermoscopy images actually makes it far better for your teledermatology services,” explained Dr. Tejasvi, who is also chief of the dermatology service at the Ann Arbor Veterans Affairs Hospital.
Why get into teledermatology?
The benefits of teledermatology include earlier diagnosis and treatment of skin cancers as documented in a Spanish study of 43,677 patients. The Spanish dermatologists reported that teledermatologically detected melanomas had a thinner Breslow depth and lower tumor stage because they were diagnosed earlier. Teledermatology also brought a twofold increase in the basal cell carcinoma detection rate and – most importantly – a reduction in time to biopsy for what turned out to be skin cancers (JAMA Dermatol. 2015 Dec 1;151[12]:1289-90).
In addition, teledermatology is an effective triage tool for busy clinicians whose appointment calendars are booked weeks or months in advance.
“Let’s say you are the only dermatologist in the surrounding five counties. You can use teledermatology to see which patients actually need to come to your clinic,” Dr. Tejasvri said. Just make sure the referring primary care providers know to send photos taken with the dermatoscope attachment.
Internet-based teledermatology also provides a way to follow patients with chronic conditions, including psoriasis, atopic dermatitis, and venous ulcers, he noted.
Before getting started
Dr. Tejasvri emphasized the importance of visiting the American Academy of Dermatology Teledermatology Task Force website as well as the American Telemedicine Association’s Teledermatology Special Interest Group, which he chairs. These resources, he stressed, are invaluable.
The AAD site, open to all academy members, includes a tool kit for getting started in teledermatology. It’s individually tailored for the dermatologist in solo, small group, academic, or multispecialty practice. This highly practical tool kit includes a checklist that aids in determining whether a dermatologist’s practice is suited for teledermatology, as well as the suggested optimal teledermatology practice model for that individual, the nuts and bolts of equipment, relevant state laws, and how to navigate legal concerns, among the most critical of which is to get in writing the malpractice insurer’s verbal reassurance that the policy covers telemedicine.
The American Telemedicine Association Teledermatology Special Interest Group provides best-practice guidelines (Telemed J E Health. 2016 Dec;22[12]:981-90)
Teledermatology practice model options
The most common teledermatology model is called “store-and-forward.” It relies upon transmission of still images of skin lesions. Its advantages are that it’s not dependent upon internet speed and it accommodates physicians working in different time zones. Most commonly, this is a consult model in which a remote primary care provider takes the photos and transmits them to the dermatologist specialist. The referring provider retains responsibility for patient care.
The other model entails creation of a virtual clinic with real-time videoconference-based communication using a HIPAA-compliant high-speed broadband internet connection. The advantages are that reimbursement is good – indeed, the same as for a face-to-face office visit – and it’s possible to ask questions of the patient and referring physician, although that’s generally not necessary for the straightforward evaluation of suspicious pigmented or nonpigmented skin lesions. However, the video image quality isn’t as good as with still photos, the virtual clinic requires dedicated scheduling, and the quality of the experience is highly dependent upon internet speed.
“If you have a bad internet speed the whole process becomes choppy. When you ask a question, the answer you get is the one to your previous question,” Dr. Tejasvi said.
Reimbursement
Currently 38 states and Washington, D.C., have laws governing private payer telehealth reimbursement policy.
Under the 2019 Medicare physician fee schedule, code number 99446 – interprofessional telephone/internet consult lasting 5-10 minutes – pays $18.36. A 99447, lasting 11-20 minutes, pays $36.36, and a 99448, representing a 21-30 minute interprofessional consult, pays $54.72.
“Reimbursement is poor. It’s not a lot at all. If you spend 5-10 minutes on a consult you get paid about 20 bucks. But it’s better than nothing, and it used to be that patients had to pay out of pocket,” the dermatologist commented.
And of course, the improved timely and efficient patient access to dermatologist evaluation of potential skin cancer that’s afforded via teledermatology helps out with the profession’s workforce shortage and responds to the common criticism that dermatologists are geographically maldistributed and treatment delayed is treatment denied.
How accurate is teledermatology?
Numerous studies have reported diagnostic concordance rates between teledermatology and face-to-face clinical diagnosis of 72.5%-90% for melanoma, dropping off markedly to 31.2%-62% for lentigines. However, teledermoscopic images greatly improved the diagnostic accuracy.
In one recent study involving teledermatology versus face-to-face evaluation of 293 index lesions, the face-to-face dermatologist examination turned up 131 incidental skin lesions, including 6 incidental melanomas not suspected or photographed by the consulting primary care providers. That worked out to a 2.6% risk of incidental melanoma per consult, which Dr. Tejasvi called “kind of scary.”
“All six of the incidental melanomas were located on the back, chest, or abdomen, so a good teaching point is that, if you’re doing a teledermatology consult, ask the primary care provider who’s sending you this consult to do a careful waist-up exam to look for other lesions,” he advised.
He added that more and larger studies are needed in order to determine the diagnostic concordance rate for nonpigmented lesions.
Dr. Tejasvi reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Initial FLAG-Ida outperforms 7+3 for high-risk AML
A treatment commonly used as a salvage regimen for relapsed/refractory acute myelogenous leukemia (AML) showed better results than did standard treatment when used as initial induction therapy.
Researchers found that the use of fludarabine, high-dose cytarabine, with granulocyte-colony stimulating factor (FLAG) – with or without idarubicin (Ida) – resulted in higher remission rates for nonfavorable risk AML patients after one course of induction, compared with standard 7+3 (anthracycline plus cytarabine) treatment.
The use of FLAG+/-Ida also resulted in a shorter time to complete remission (CR) and a shorter time to transplant, compared with 7+3. Additionally, postremission overall survival (OS) and disease-free survival (DFS) were better after achieving CR from FLAG-Ida, compared with 7+3, Melhem Solh, MD, of the Blood & Marrow Transplant Program at Northside Hospital, Atlanta, and colleagues reported in Leukemia Research.
The researchers retrospectively analyzed 304 consecutive AML patients, with nonfavorable National Comprehensive Cancer Network (NCCN) risk who received initial treatment at their center with either 7+3 (86 patients) or FLAG+/-Ida (218 patients). They found that patients in the FLAG+/-Ida group were more likely to achieve remission after one course of induction (74% vs. 62%; P less than .001) and had a faster time to achieve CR (30 days vs. 37.5 days; P less than .001), compared with patients receiving 7+3.
The time from diagnosis to allogeneic hematopoietic cell transplantation was shorter among CR patients after FLAG+/-Ida, compared with 7+3 (115 days vs. 151 days; P less than .003).
Additionally, the 3-year postremission OS and DFS were significantly better for patients receiving FLAG-Ida at 54% and 49%, compared with 39% and 32% for 7+3, respectively (P = .01).
Dr. Solh and colleagues found that the factors associated with postremission survival included age at first CR, NCCN risk, induction regimen (FLAG+/-Ida vs. 7+3; hazard ratio, 0.62; P = .01), and receipt of allogeneic hematopoietic cell transplantation.
“FLAG-Ida is a more efficacious regimen when used for initial induction compared to 3+7. It appears to produce better survival and improved postremission survival for AML patients with intermediate and poor risk AML without increasing toxicity,” Dr. Solh and colleagues wrote. “Further validation of these results in a well-designed randomized prospective trial will help define the best induction approaches for AML.”
There was no outside funding for this research and the authors reported that they had no relevant financial conflicts.
SOURCE: Solh MM et al. Leuk Res. 2020 Feb 14. doi: 10.1016/j.leukres.2020.106318.
A treatment commonly used as a salvage regimen for relapsed/refractory acute myelogenous leukemia (AML) showed better results than did standard treatment when used as initial induction therapy.
Researchers found that the use of fludarabine, high-dose cytarabine, with granulocyte-colony stimulating factor (FLAG) – with or without idarubicin (Ida) – resulted in higher remission rates for nonfavorable risk AML patients after one course of induction, compared with standard 7+3 (anthracycline plus cytarabine) treatment.
The use of FLAG+/-Ida also resulted in a shorter time to complete remission (CR) and a shorter time to transplant, compared with 7+3. Additionally, postremission overall survival (OS) and disease-free survival (DFS) were better after achieving CR from FLAG-Ida, compared with 7+3, Melhem Solh, MD, of the Blood & Marrow Transplant Program at Northside Hospital, Atlanta, and colleagues reported in Leukemia Research.
The researchers retrospectively analyzed 304 consecutive AML patients, with nonfavorable National Comprehensive Cancer Network (NCCN) risk who received initial treatment at their center with either 7+3 (86 patients) or FLAG+/-Ida (218 patients). They found that patients in the FLAG+/-Ida group were more likely to achieve remission after one course of induction (74% vs. 62%; P less than .001) and had a faster time to achieve CR (30 days vs. 37.5 days; P less than .001), compared with patients receiving 7+3.
The time from diagnosis to allogeneic hematopoietic cell transplantation was shorter among CR patients after FLAG+/-Ida, compared with 7+3 (115 days vs. 151 days; P less than .003).
Additionally, the 3-year postremission OS and DFS were significantly better for patients receiving FLAG-Ida at 54% and 49%, compared with 39% and 32% for 7+3, respectively (P = .01).
Dr. Solh and colleagues found that the factors associated with postremission survival included age at first CR, NCCN risk, induction regimen (FLAG+/-Ida vs. 7+3; hazard ratio, 0.62; P = .01), and receipt of allogeneic hematopoietic cell transplantation.
“FLAG-Ida is a more efficacious regimen when used for initial induction compared to 3+7. It appears to produce better survival and improved postremission survival for AML patients with intermediate and poor risk AML without increasing toxicity,” Dr. Solh and colleagues wrote. “Further validation of these results in a well-designed randomized prospective trial will help define the best induction approaches for AML.”
There was no outside funding for this research and the authors reported that they had no relevant financial conflicts.
SOURCE: Solh MM et al. Leuk Res. 2020 Feb 14. doi: 10.1016/j.leukres.2020.106318.
A treatment commonly used as a salvage regimen for relapsed/refractory acute myelogenous leukemia (AML) showed better results than did standard treatment when used as initial induction therapy.
Researchers found that the use of fludarabine, high-dose cytarabine, with granulocyte-colony stimulating factor (FLAG) – with or without idarubicin (Ida) – resulted in higher remission rates for nonfavorable risk AML patients after one course of induction, compared with standard 7+3 (anthracycline plus cytarabine) treatment.
The use of FLAG+/-Ida also resulted in a shorter time to complete remission (CR) and a shorter time to transplant, compared with 7+3. Additionally, postremission overall survival (OS) and disease-free survival (DFS) were better after achieving CR from FLAG-Ida, compared with 7+3, Melhem Solh, MD, of the Blood & Marrow Transplant Program at Northside Hospital, Atlanta, and colleagues reported in Leukemia Research.
The researchers retrospectively analyzed 304 consecutive AML patients, with nonfavorable National Comprehensive Cancer Network (NCCN) risk who received initial treatment at their center with either 7+3 (86 patients) or FLAG+/-Ida (218 patients). They found that patients in the FLAG+/-Ida group were more likely to achieve remission after one course of induction (74% vs. 62%; P less than .001) and had a faster time to achieve CR (30 days vs. 37.5 days; P less than .001), compared with patients receiving 7+3.
The time from diagnosis to allogeneic hematopoietic cell transplantation was shorter among CR patients after FLAG+/-Ida, compared with 7+3 (115 days vs. 151 days; P less than .003).
Additionally, the 3-year postremission OS and DFS were significantly better for patients receiving FLAG-Ida at 54% and 49%, compared with 39% and 32% for 7+3, respectively (P = .01).
Dr. Solh and colleagues found that the factors associated with postremission survival included age at first CR, NCCN risk, induction regimen (FLAG+/-Ida vs. 7+3; hazard ratio, 0.62; P = .01), and receipt of allogeneic hematopoietic cell transplantation.
“FLAG-Ida is a more efficacious regimen when used for initial induction compared to 3+7. It appears to produce better survival and improved postremission survival for AML patients with intermediate and poor risk AML without increasing toxicity,” Dr. Solh and colleagues wrote. “Further validation of these results in a well-designed randomized prospective trial will help define the best induction approaches for AML.”
There was no outside funding for this research and the authors reported that they had no relevant financial conflicts.
SOURCE: Solh MM et al. Leuk Res. 2020 Feb 14. doi: 10.1016/j.leukres.2020.106318.
FROM LEUKEMIA RESEARCH
New leaders at SKCC, Mount Sinai, NHF
The Sidney Kimmel Cancer Center–Jefferson Health (SKCC) has a new director of bone marrow transplant and cell-based therapy, Mount Sinai has a new head of clinical cancer research, and the National Hemophilia Foundation (NHF) has a new president and CEO.
Usama Gergis, MD, has joined SKCC in Philadelphia as director of the bone marrow transplant and immune cellular therapy program and as a professor in the department of medical oncology, division of hematological malignancies.
Dr. Gergis came to SKCC from Weill Cornell Medicine in New York, where he helped expand the use of umbilical cord blood transplant and established an immune cellular therapy program. He also established and led one of the largest oncology international medicine programs in the United States.
Dr. Gergis earned his medical degree from Cairo (Egypt) University. He completed an internal medicine residency and a hematology/oncology fellowship at the Brooklyn Hospital of Weill Cornell. He also completed a bone marrow transplant fellowship at the Moffitt Cancer Center in Tampa.
Karyn Aalami Goodman, MD, has been hired to lead clinical cancer research at Mount Sinai, New York. She is now the associate director for clinical research at the Tisch Cancer Institute and a professor and vice-chair for research and quality in the department of radiation oncology. In these roles, she will develop the infrastructure and resources to support clinical trials of cancer patients.
Dr. Goodman’s own research is focused on improving outcomes for patients with gastrointestinal malignancies. She has helped develop protocols combining radiation, chemotherapy, targeted agents, and immunotherapy.
Dr. Goodman earned her medical degree from Stanford (Calif.) University. She completed an internship in internal medicine at Stanford and residency training in radiation oncology at Memorial Sloan-Kettering Cancer Center in New York. She was previously associate director of clinical research at the University of Colorado Cancer Center in Aurora.
Leonard A. Valentino, MD, has assumed the role of president and CEO of the National Hemophilia Foundation in New York. In this role, Dr. Valentino will “work to advance the foundation’s mission of education, advocacy, and research,” according to the NHF.
Dr. Valentino previously held leadership roles at Spark Therapeutics, Shire, Baxalta, and Baxter Healthcare Corporation. Prior to that, he founded and led the Hemophilia and Thrombophilia Center at Rush University Medical Center in Chicago.
Dr. Valentino earned his undergraduate and medical degrees from Creighton University in Omaha, Neb. He completed his residency at the University of Illinois at Chicago and a fellowship in pediatric hematology-oncology at the University of California, Los Angeles .
The Sidney Kimmel Cancer Center–Jefferson Health (SKCC) has a new director of bone marrow transplant and cell-based therapy, Mount Sinai has a new head of clinical cancer research, and the National Hemophilia Foundation (NHF) has a new president and CEO.
Usama Gergis, MD, has joined SKCC in Philadelphia as director of the bone marrow transplant and immune cellular therapy program and as a professor in the department of medical oncology, division of hematological malignancies.
Dr. Gergis came to SKCC from Weill Cornell Medicine in New York, where he helped expand the use of umbilical cord blood transplant and established an immune cellular therapy program. He also established and led one of the largest oncology international medicine programs in the United States.
Dr. Gergis earned his medical degree from Cairo (Egypt) University. He completed an internal medicine residency and a hematology/oncology fellowship at the Brooklyn Hospital of Weill Cornell. He also completed a bone marrow transplant fellowship at the Moffitt Cancer Center in Tampa.
Karyn Aalami Goodman, MD, has been hired to lead clinical cancer research at Mount Sinai, New York. She is now the associate director for clinical research at the Tisch Cancer Institute and a professor and vice-chair for research and quality in the department of radiation oncology. In these roles, she will develop the infrastructure and resources to support clinical trials of cancer patients.
Dr. Goodman’s own research is focused on improving outcomes for patients with gastrointestinal malignancies. She has helped develop protocols combining radiation, chemotherapy, targeted agents, and immunotherapy.
Dr. Goodman earned her medical degree from Stanford (Calif.) University. She completed an internship in internal medicine at Stanford and residency training in radiation oncology at Memorial Sloan-Kettering Cancer Center in New York. She was previously associate director of clinical research at the University of Colorado Cancer Center in Aurora.
Leonard A. Valentino, MD, has assumed the role of president and CEO of the National Hemophilia Foundation in New York. In this role, Dr. Valentino will “work to advance the foundation’s mission of education, advocacy, and research,” according to the NHF.
Dr. Valentino previously held leadership roles at Spark Therapeutics, Shire, Baxalta, and Baxter Healthcare Corporation. Prior to that, he founded and led the Hemophilia and Thrombophilia Center at Rush University Medical Center in Chicago.
Dr. Valentino earned his undergraduate and medical degrees from Creighton University in Omaha, Neb. He completed his residency at the University of Illinois at Chicago and a fellowship in pediatric hematology-oncology at the University of California, Los Angeles .
The Sidney Kimmel Cancer Center–Jefferson Health (SKCC) has a new director of bone marrow transplant and cell-based therapy, Mount Sinai has a new head of clinical cancer research, and the National Hemophilia Foundation (NHF) has a new president and CEO.
Usama Gergis, MD, has joined SKCC in Philadelphia as director of the bone marrow transplant and immune cellular therapy program and as a professor in the department of medical oncology, division of hematological malignancies.
Dr. Gergis came to SKCC from Weill Cornell Medicine in New York, where he helped expand the use of umbilical cord blood transplant and established an immune cellular therapy program. He also established and led one of the largest oncology international medicine programs in the United States.
Dr. Gergis earned his medical degree from Cairo (Egypt) University. He completed an internal medicine residency and a hematology/oncology fellowship at the Brooklyn Hospital of Weill Cornell. He also completed a bone marrow transplant fellowship at the Moffitt Cancer Center in Tampa.
Karyn Aalami Goodman, MD, has been hired to lead clinical cancer research at Mount Sinai, New York. She is now the associate director for clinical research at the Tisch Cancer Institute and a professor and vice-chair for research and quality in the department of radiation oncology. In these roles, she will develop the infrastructure and resources to support clinical trials of cancer patients.
Dr. Goodman’s own research is focused on improving outcomes for patients with gastrointestinal malignancies. She has helped develop protocols combining radiation, chemotherapy, targeted agents, and immunotherapy.
Dr. Goodman earned her medical degree from Stanford (Calif.) University. She completed an internship in internal medicine at Stanford and residency training in radiation oncology at Memorial Sloan-Kettering Cancer Center in New York. She was previously associate director of clinical research at the University of Colorado Cancer Center in Aurora.
Leonard A. Valentino, MD, has assumed the role of president and CEO of the National Hemophilia Foundation in New York. In this role, Dr. Valentino will “work to advance the foundation’s mission of education, advocacy, and research,” according to the NHF.
Dr. Valentino previously held leadership roles at Spark Therapeutics, Shire, Baxalta, and Baxter Healthcare Corporation. Prior to that, he founded and led the Hemophilia and Thrombophilia Center at Rush University Medical Center in Chicago.
Dr. Valentino earned his undergraduate and medical degrees from Creighton University in Omaha, Neb. He completed his residency at the University of Illinois at Chicago and a fellowship in pediatric hematology-oncology at the University of California, Los Angeles .
Key to denervation response for hypertension may be in carotid body
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.
The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.
For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.
Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.
“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.
The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.
In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).
Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.
However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.
In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.
Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.
To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.
Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.
Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.
In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.
A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”
Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.
This article was updated to clarify the study details and correct misspellings of the presenter's name.
SOURCE: CRT 2020.
REPORTING FROM CRT 2020
FDA, FTC uniting to promote biosimilars
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
Vitamin D supplements in pregnancy boost bone health in offspring
Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.
“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D3 (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D3.
The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.
At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.
The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.
At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.
Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm2 greater total BMD, compared with those with sufficient vitamin D at baseline.
Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm2 higher head BMD, and a mean 12-g higher total BMC.
Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.
The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.
There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.
“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.
Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.
Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.
“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”
She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.
Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.
“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”
Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.
The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.
SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.
Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.
“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D3 (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D3.
The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.
At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.
The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.
At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.
Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm2 greater total BMD, compared with those with sufficient vitamin D at baseline.
Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm2 higher head BMD, and a mean 12-g higher total BMC.
Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.
The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.
There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.
“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.
Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.
Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.
“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”
She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.
Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.
“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”
Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.
The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.
SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.
Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.
“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D3 (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D3.
The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.
At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.
The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.
At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.
Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm2 greater total BMD, compared with those with sufficient vitamin D at baseline.
Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm2 higher head BMD, and a mean 12-g higher total BMC.
Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.
The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.
There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.
“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.
Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.
Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.
“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”
She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.
Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.
“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”
Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.
The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.
SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.
FROM JAMA PEDIATRICS
FDA approves first IV migraine prevention drug
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
FROM MEDSCAPE.COM
Irinotecan shows promise for triple-negative breast cancer
The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.
Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.
Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.
Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).
The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.
The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.
The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.
“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.
They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.
“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.
The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.
SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.
The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.
Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.
Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.
Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).
The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.
The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.
The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.
“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.
They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.
“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.
The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.
SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.
The topoisomerase I (TOP1) inhibitor irinotecan could be effective in treating triple-negative breast cancer (TNBC), according to results from a preclinical study published in Science Translational Medicine.
Florence Coussy, MD, PhD, of Institut Curie, Paris, and colleagues evaluated the antitumor activity of the Food and Drug Administration–approved TOP1 inhibitor irinotecan in 40 patient-derived xenografts (PDXs) of TNBC.
Other treatments, such as noncamptothecin TOP1 inhibitors (indotecan and indimitecan) and irinotecan plus VE-822 (an ataxia telangiectasia and Rad3-related protein [ATR] inhibitor), were also evaluated in the PDX models.
Tumor samples were collected from patients with primary breast cancer at the time of surgery (55%), residual breast cancer after neoadjuvant treatment (40%), or axillary lymph node metastases (5%). The patients had a mean age of 56 years (range, 29-89 years).
The researchers assessed BRCAness using the homologous recombination deficiency–large-scale state transition assay. Additional potential markers of response, including expression of retinoblastoma transcriptional corepressor 1 (RB1) and Schlafen family member 11 (SLFN11), were detected on transcriptomic analysis and validated using immunohistochemistry analyses.
The researchers found that 37.5% (n = 15) of TNBC PDX models achieved a partial or complete response to irinotecan therapy, while 22.5% (n = 9) of models had stable disease. BRCAness, RB1 loss, and high SLFN11 expression were deemed potential markers of response to irinotecan and other clinical TOP1 inhibitors.
The researchers then evaluated 250 breast cancer patients treated with anthracycline-based chemotherapy and found that lower expression of SLFN11 was associated with worse survival.
“We also [found] that, in the absence of SLFN11, response to irinotecan can be increased by adding an ATR inhibitor and that the clinical TOP1 inhibitors are highly efficient in BRCA1-mutant and BRCAness-positive TNBC PDXs,” the researchers reported.
They acknowledged that a key limitation of this study was the absence of tumor samples from patients who had received a TOP1 inhibitor.
“Overall, our findings are in line with the notion that concomitant defects in DNA repair and checkpoints render cancer cells highly vulnerable to TOP1 inhibitors,” the researchers concluded.
The study was funded by the National Cancer Institute, PIC3i NCI-Curie, and Site de Recherche Intégrée sur le Cancer. One author is an inventor of indotecan and indimitecan. Two authors are coinventors of the method used to detect inactivation of the homologous recombination pathway, which is licensed to Myriad Genetics.
SOURCE: Coussy F et al. Sci Transl Med. 2020 Feb 19. doi: 10.1126/scitranslmed.aax2625.
FROM SCIENCE TRANSLATIONAL MEDICINE